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Yeast-2-Hybrid (Y2H) assays validated the physical interaction between CcNAC1 and KCS. The results provide relatively comprehensive information on the molecular mechanisms of CcNAC1 gene underlying the regulation of plant growth and drought stress resistance, and indicate that CcNAC1 acts as a positive regulator in drought tolerance in jute (Corchorus capsularis L.).The unfolded helix is an ear deformity more frequent than expected. It might be presented alone or combined with other scapha or concha anomalies, giving the appearance of big and prominent ears. https://www.selleckchem.com/products/nps-2143.html Currently, there are few reports published about its restoration and few modifications have been made to its original surgical approaches since the 1970s. The technique herein described aims to facilitate the helix rim restoration procedure by considering the following preoperative and surgical advices. The preoperative use of the pinch test allows to better understand the patients' expectations, helps to explain the future outcomes to them and simplifies the marking of the tissue to be removed. The additional bilateral only-cartilage resections and the maintenance of the skin excess permit to optimize the cosmetic outcomes. This innovative surgical approach for the helix rim restoration is reliable, has little morbidity associated and presents consistent effective results. LEVEL OF EVIDENCE V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
The true effect of aging and other patient factors on submandibular gland (SMG) volume is unclear. We sought to evaluate the effects of age, body mass index (BMI), sex and race on SMG volume using computed tomography (CT) imaging.
We conducted a retrospective longitudinal study of adult subjects with multiple CT images of the neck at least 7 years apart. Subjects with history of salivary gland pathology, neck dissection, head and neck radiation, active infection or dental artifact were excluded. Three-dimensional volumes were measured. Age, BMI, sex and race data were analyzed to track their longitudinal effect on SMG volume.
The study comprised 64 patients (Females n=36; Males n=28) with mean age of 47.1 and 58.5 at each respective time point (mean difference 11.4). Mean SMG volume increased from 10.1 ml to 10.5ml (P < 0.05). Males had significantly greater SMG volume compared to females. Majority of growth occurred in the < 40year age bracket (0.1ml/year), more significantly in the male cohort. When controlling for aging and sex, a change in BMI was the only patient factor that predicted a change in SMG volume. An increase of 1.0kg/m
predicted a 0.17ml increase in gland volume. Race had no significant effect.
Our findings suggest that the majority of SMG volume change occurs in early adulthood ( < 40 years), especially in males. Among the factors we studied, a change in BMI was the only significant predictor of SMG volume change.
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 . Genital Surgery.
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 . Genital Surgery.To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after HDC/ASCT are given. This guideline not only focuses on patients with haematological malignancies but also addresses the specifics of HDC/ASCT patients with solid tumours or autoimmune disorders. In addition to HBV and HCV, HEV screening is nowadays mandatory prior to ASCT. For patients with HBs antigen and/or anti-HBc antibody positivity, HBV nucleic acid testing is strongly recommended for 6 months after HDC/ASCT or for the duration of a respective maintenance therapy. Prevention of VZV reactivation by vaccination is strongly recommended. Cotrimoxazole for the prevention of Pneumocystis jirovecii is supported. Invasive fungal diseases are less frequent after HDC/ASCT, therefore, primary systemic antifungal prophylaxis is not recommended. Data do not support a benefit of protective room ventilation e.g. HEPA filtration. Thus, AGIHO only supports this technique with marginal strength. Fluoroquinolone prophylaxis is recommended to prevent bacterial infections, although a survival advantage has not been demonstrated.Abnormal blood coagulation often occurs in critically ill patients, which seriously affects their prognosis. This retrospective study investigated the implications of changes in blood coagulation in patients with coronavirus disease 2019 (COVID-19). Records were reviewed for patients admitted with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital death. A total of 85 patients were included, of whom 12 died in the hospital. The admission prothrombin time (PT), international normalized ratio (INR), and levels of D-dimer and fibrin/fibrinogen degradation products (FDP) were significantly higher in non-survivors than in survivors, while the reverse was true for prothrombin time activity (PT-act) and PaO2/FiO2. Multivariate logistic regression showed that PT-act less then 75% was independently associated with mortality. The area under the receiver operating characteristic curves for PT-act, D-dimer, and FDP at admission could significantly predict mortality. The AUCs for PT-act were larger than those for D-dimer and FDP; however, there was no significant difference. After 2 weeks of treatment, the coagulation parameters of the surviving patients improved. COVID-19 is often accompanied by abnormal coagulation. PT-act at admission is able to predict mortality in patients with COVID-19 as can D-dimer and FDP levels. PT-act less then 75% is independently associated with mortality.
Yeast-2-Hybrid (Y2H) assays validated the physical interaction between CcNAC1 and KCS. The results provide relatively comprehensive information on the molecular mechanisms of CcNAC1 gene underlying the regulation of plant growth and drought stress resistance, and indicate that CcNAC1 acts as a positive regulator in drought tolerance in jute (Corchorus capsularis L.).The unfolded helix is an ear deformity more frequent than expected. It might be presented alone or combined with other scapha or concha anomalies, giving the appearance of big and prominent ears. https://www.selleckchem.com/products/nps-2143.html Currently, there are few reports published about its restoration and few modifications have been made to its original surgical approaches since the 1970s. The technique herein described aims to facilitate the helix rim restoration procedure by considering the following preoperative and surgical advices. The preoperative use of the pinch test allows to better understand the patients' expectations, helps to explain the future outcomes to them and simplifies the marking of the tissue to be removed. The additional bilateral only-cartilage resections and the maintenance of the skin excess permit to optimize the cosmetic outcomes. This innovative surgical approach for the helix rim restoration is reliable, has little morbidity associated and presents consistent effective results. LEVEL OF EVIDENCE V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . The true effect of aging and other patient factors on submandibular gland (SMG) volume is unclear. We sought to evaluate the effects of age, body mass index (BMI), sex and race on SMG volume using computed tomography (CT) imaging. We conducted a retrospective longitudinal study of adult subjects with multiple CT images of the neck at least 7 years apart. Subjects with history of salivary gland pathology, neck dissection, head and neck radiation, active infection or dental artifact were excluded. Three-dimensional volumes were measured. Age, BMI, sex and race data were analyzed to track their longitudinal effect on SMG volume. The study comprised 64 patients (Females n=36; Males n=28) with mean age of 47.1 and 58.5 at each respective time point (mean difference 11.4). Mean SMG volume increased from 10.1 ml to 10.5ml (P < 0.05). Males had significantly greater SMG volume compared to females. Majority of growth occurred in the < 40year age bracket (0.1ml/year), more significantly in the male cohort. When controlling for aging and sex, a change in BMI was the only patient factor that predicted a change in SMG volume. An increase of 1.0kg/m predicted a 0.17ml increase in gland volume. Race had no significant effect. Our findings suggest that the majority of SMG volume change occurs in early adulthood ( < 40 years), especially in males. Among the factors we studied, a change in BMI was the only significant predictor of SMG volume change. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 . Genital Surgery. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 . Genital Surgery.To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after HDC/ASCT are given. This guideline not only focuses on patients with haematological malignancies but also addresses the specifics of HDC/ASCT patients with solid tumours or autoimmune disorders. In addition to HBV and HCV, HEV screening is nowadays mandatory prior to ASCT. For patients with HBs antigen and/or anti-HBc antibody positivity, HBV nucleic acid testing is strongly recommended for 6 months after HDC/ASCT or for the duration of a respective maintenance therapy. Prevention of VZV reactivation by vaccination is strongly recommended. Cotrimoxazole for the prevention of Pneumocystis jirovecii is supported. Invasive fungal diseases are less frequent after HDC/ASCT, therefore, primary systemic antifungal prophylaxis is not recommended. Data do not support a benefit of protective room ventilation e.g. HEPA filtration. Thus, AGIHO only supports this technique with marginal strength. Fluoroquinolone prophylaxis is recommended to prevent bacterial infections, although a survival advantage has not been demonstrated.Abnormal blood coagulation often occurs in critically ill patients, which seriously affects their prognosis. This retrospective study investigated the implications of changes in blood coagulation in patients with coronavirus disease 2019 (COVID-19). Records were reviewed for patients admitted with COVID-19 between February 4 and 16, 2020. The primary outcome was in-hospital death. A total of 85 patients were included, of whom 12 died in the hospital. The admission prothrombin time (PT), international normalized ratio (INR), and levels of D-dimer and fibrin/fibrinogen degradation products (FDP) were significantly higher in non-survivors than in survivors, while the reverse was true for prothrombin time activity (PT-act) and PaO2/FiO2. Multivariate logistic regression showed that PT-act less then 75% was independently associated with mortality. The area under the receiver operating characteristic curves for PT-act, D-dimer, and FDP at admission could significantly predict mortality. The AUCs for PT-act were larger than those for D-dimer and FDP; however, there was no significant difference. After 2 weeks of treatment, the coagulation parameters of the surviving patients improved. COVID-19 is often accompanied by abnormal coagulation. PT-act at admission is able to predict mortality in patients with COVID-19 as can D-dimer and FDP levels. PT-act less then 75% is independently associated with mortality.0 Comments 0 Shares 546 Views 0 ReviewsPlease log in to like, share and comment! -
This research article describes an approach to modify the thiazolidinedione scaffold to produce test drugs capable of binding to, and inhibit, the in vitro transcriptional activity of the oncogenic protein FOXM1. This approach allowed us to obtain FOXM1 inhibitors that bind directly to the FOXM1-DNA binding domain without targeting the expression levels of Sp1, an upstream transcription factor protein known to activate the expression of FOXM1. Briefly, we modified the chemical structure of the thiazolidinedione scaffold present in anti-diabetic medications such as pioglitazone, rosiglitazone and the former anti-diabetic drug troglitazone, because these drugs have been reported to exert inhibition of FOXM1 but hit other targets as well. After the chemical synthesis of 11 derivatives possessing a modified thiazolidinedione moiety, we screened all test compounds using in vitro protocols to measure their ability to (a) dissociate a FOXM1-DNA complex (EMSA assay); (b) decrease the expression of FOXM1 in triple negative-breast cancer cells (WB assay); (c) downregulate the expression of FOXM1 downstream targets (luciferase reporter assays and qPCR); and inhibit the formation of colonies of MDA-MB-231 cancer cells (colony formation assay). We also identified a potential binding mode associated with these compounds in which compound TFI-10, one of the most active molecules, exerts binding interactions with Arg289, Trp308, and His287. Unlike the parent drug, troglitazone, compound TFI-10 does not target the in vitro expression of Sp1, suggesting that it is possible to design FOXM1 inhibitors with a better selectivity profile.N-(5-Chlorobenzo[d]oxazol-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamideox-amide has been identified as a potent inhibitor of Mtb H37Rv, with a minimum inhibitory concentration (MIC) of 0.42 μM. In this study, a series of substituted 2-acylamide-1,3-zole analogues were designed and synthesized, and their anti-Mtb activities were analyzed. In total, 17 compounds were found to be potent anti-Mtb agents, especially against the MDR- and XDR-MTB strains, with ****values less then 10 μM. These analogues can inhibit both drug-sensitive and drug-resistant Mtb. Four representative compounds were selected for further profiling, and the results indicate that compound 18 is acceptably safe and has favorable pharmacokinetic (PK) properties. In addition, this compound displays potent activity against Gram-positive bacteria, with ****values in the range of 1.48-11.86 μM. The data obtained herein suggest that promising anti-Mtb candidates may be developed via structural modification, and that further research is needed to explore other compounds.Kidney fibrosis is the common consequence of chronic kidney diseases that inexorably progresses to end-stage kidney disease with organ failure treatable only with replacement therapy. Since transforming growth factor-β1 is the main player in the pathogenesis of kidney fibrosis, we posed the hypothesis that recombinant thrombomodulin can ameliorate transforming growth factor-β1-mediated progressive kidney fibrosis and failure. To interrogate our hypothesis, we generated a novel glomerulus-specific human transforming growth factor-β1 transgenic mouse to evaluate the therapeutic effect of recombinant thrombomodulin. This transgenic mouse developed progressive glomerular sclerosis and tubulointerstitial fibrosis with kidney failure. Therapy with recombinant thrombomodulin for four weeks significantly inhibited kidney fibrosis and improved organ function compared to untreated transgenic ****. Treatment with recombinant thrombomodulin significantly inhibited apoptosis and mesenchymal differentiation of podocytes by interacting with the G-protein coupled receptor 15 to activate the Akt signaling pathway and to upregulate the expression of anti-apoptotic proteins including survivin. Thus, our study strongly suggests the potential therapeutic efficacy of recombinant thrombomodulin for the treatment of chronic kidney disease and subsequent organ failure.Bovine tuberculosis (bTB) can be spread between and among cattle and wildlife hosts e.g. European badger (Meles meles). The majority of cattle in the UK and Ireland are grazed during the summer, potentially exposing them to Mycobacterium bovis. 18 farms were surveyed (39% dairy, 61% beef; fields n = 697) for one grazing season (May-November 2016, n = 148,461 field days) to quantify the co-occurrence of cattle with badger setts and latrines and adjacency to neighbouring cattle herds. 3% (n = 24) of the fields had a badger sett or latrine recorded, dairy cattle were significantly more likely to co-occur with badger setts and latrines than beef cattle. Most farms (89%) grazed cattle adjacent to a neighbouring herd, which accounted for 18% of the grazing season. Potential exposure to neighbouring herds did not differ between production systems but did vary between life stages. A significant positive association between the proportion of time cattle spent grazing fields with setts present and the historic 1-, 3- and 5- year bTB status (p = 0.007, p = 0.013 and p = 0.013 respectively) was found. However, when cattle were grazed in fields with latrines, a significant negative association was found between the proportion of time cattle spent grazing fields with latrines present and the historic 3- and 5- year bTB status (p = 0.033 and p = 0.012 respectively). https://www.selleckchem.com/products/dzd9008.html Historic bTB status and percentage of days spent beside a neighbouring herd was unrelated. Idiosyncrasies at farm-level and between risk factors indicated that individual farm assessments would be beneficial to understand potential exposure risk.
To explore the currently unknown association between history of cancer at the time of coronary artery bypass grafting (CABG) and long-term survival.
All patients (n=82,137) undergoing isolated first-time CABG in Sweden during 1997-2015 were included in this retrospective population-based cohort study. Individual patient data from the SWEDEHEART registry and 4 other mandatory nationwide health care registries were merged. Multivariable Cox proportional hazards regression and competing risk models adjusted for age and gender were used to assess associations between history of cancer, and long-term all-cause, cardiovascular and cancer mortality. Median follow-up was 9.0years (interquartile range, 4.8-13.1).
Altogether, 6819 (8.3%) of the patients had a history of cancer. The annual prevalence increased from 3.8% in 1997 to 14.8% in 2015. Patients with a history of cancer were older (72 vs 66years; P<.001) and had more comorbidities. Long-term all-cause mortality was significantly greater in patients with a history of cancer (45.
This research article describes an approach to modify the thiazolidinedione scaffold to produce test drugs capable of binding to, and inhibit, the in vitro transcriptional activity of the oncogenic protein FOXM1. This approach allowed us to obtain FOXM1 inhibitors that bind directly to the FOXM1-DNA binding domain without targeting the expression levels of Sp1, an upstream transcription factor protein known to activate the expression of FOXM1. Briefly, we modified the chemical structure of the thiazolidinedione scaffold present in anti-diabetic medications such as pioglitazone, rosiglitazone and the former anti-diabetic drug troglitazone, because these drugs have been reported to exert inhibition of FOXM1 but hit other targets as well. After the chemical synthesis of 11 derivatives possessing a modified thiazolidinedione moiety, we screened all test compounds using in vitro protocols to measure their ability to (a) dissociate a FOXM1-DNA complex (EMSA assay); (b) decrease the expression of FOXM1 in triple negative-breast cancer cells (WB assay); (c) downregulate the expression of FOXM1 downstream targets (luciferase reporter assays and qPCR); and inhibit the formation of colonies of MDA-MB-231 cancer cells (colony formation assay). We also identified a potential binding mode associated with these compounds in which compound TFI-10, one of the most active molecules, exerts binding interactions with Arg289, Trp308, and His287. Unlike the parent drug, troglitazone, compound TFI-10 does not target the in vitro expression of Sp1, suggesting that it is possible to design FOXM1 inhibitors with a better selectivity profile.N-(5-Chlorobenzo[d]oxazol-2-yl)-4-methyl-1,2,3-thiadiazole-5-carboxamideox-amide has been identified as a potent inhibitor of Mtb H37Rv, with a minimum inhibitory concentration (MIC) of 0.42 μM. In this study, a series of substituted 2-acylamide-1,3-zole analogues were designed and synthesized, and their anti-Mtb activities were analyzed. In total, 17 compounds were found to be potent anti-Mtb agents, especially against the MDR- and XDR-MTB strains, with MIC values less then 10 μM. These analogues can inhibit both drug-sensitive and drug-resistant Mtb. Four representative compounds were selected for further profiling, and the results indicate that compound 18 is acceptably safe and has favorable pharmacokinetic (PK) properties. In addition, this compound displays potent activity against Gram-positive bacteria, with MIC values in the range of 1.48-11.86 μM. The data obtained herein suggest that promising anti-Mtb candidates may be developed via structural modification, and that further research is needed to explore other compounds.Kidney fibrosis is the common consequence of chronic kidney diseases that inexorably progresses to end-stage kidney disease with organ failure treatable only with replacement therapy. Since transforming growth factor-β1 is the main player in the pathogenesis of kidney fibrosis, we posed the hypothesis that recombinant thrombomodulin can ameliorate transforming growth factor-β1-mediated progressive kidney fibrosis and failure. To interrogate our hypothesis, we generated a novel glomerulus-specific human transforming growth factor-β1 transgenic mouse to evaluate the therapeutic effect of recombinant thrombomodulin. This transgenic mouse developed progressive glomerular sclerosis and tubulointerstitial fibrosis with kidney failure. Therapy with recombinant thrombomodulin for four weeks significantly inhibited kidney fibrosis and improved organ function compared to untreated transgenic mice. Treatment with recombinant thrombomodulin significantly inhibited apoptosis and mesenchymal differentiation of podocytes by interacting with the G-protein coupled receptor 15 to activate the Akt signaling pathway and to upregulate the expression of anti-apoptotic proteins including survivin. Thus, our study strongly suggests the potential therapeutic efficacy of recombinant thrombomodulin for the treatment of chronic kidney disease and subsequent organ failure.Bovine tuberculosis (bTB) can be spread between and among cattle and wildlife hosts e.g. European badger (Meles meles). The majority of cattle in the UK and Ireland are grazed during the summer, potentially exposing them to Mycobacterium bovis. 18 farms were surveyed (39% dairy, 61% beef; fields n = 697) for one grazing season (May-November 2016, n = 148,461 field days) to quantify the co-occurrence of cattle with badger setts and latrines and adjacency to neighbouring cattle herds. 3% (n = 24) of the fields had a badger sett or latrine recorded, dairy cattle were significantly more likely to co-occur with badger setts and latrines than beef cattle. Most farms (89%) grazed cattle adjacent to a neighbouring herd, which accounted for 18% of the grazing season. Potential exposure to neighbouring herds did not differ between production systems but did vary between life stages. A significant positive association between the proportion of time cattle spent grazing fields with setts present and the historic 1-, 3- and 5- year bTB status (p = 0.007, p = 0.013 and p = 0.013 respectively) was found. However, when cattle were grazed in fields with latrines, a significant negative association was found between the proportion of time cattle spent grazing fields with latrines present and the historic 3- and 5- year bTB status (p = 0.033 and p = 0.012 respectively). https://www.selleckchem.com/products/dzd9008.html Historic bTB status and percentage of days spent beside a neighbouring herd was unrelated. Idiosyncrasies at farm-level and between risk factors indicated that individual farm assessments would be beneficial to understand potential exposure risk. To explore the currently unknown association between history of cancer at the time of coronary artery bypass grafting (CABG) and long-term survival. All patients (n=82,137) undergoing isolated first-time CABG in Sweden during 1997-2015 were included in this retrospective population-based cohort study. Individual patient data from the SWEDEHEART registry and 4 other mandatory nationwide health care registries were merged. Multivariable Cox proportional hazards regression and competing risk models adjusted for age and gender were used to assess associations between history of cancer, and long-term all-cause, cardiovascular and cancer mortality. Median follow-up was 9.0years (interquartile range, 4.8-13.1). Altogether, 6819 (8.3%) of the patients had a history of cancer. The annual prevalence increased from 3.8% in 1997 to 14.8% in 2015. Patients with a history of cancer were older (72 vs 66years; P<.001) and had more comorbidities. Long-term all-cause mortality was significantly greater in patients with a history of cancer (45.0 Comments 0 Shares 186 Views 0 Reviews -
Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory tract infections (ARTIs) in children less than 5 years, second only to human respiratory syncytial viruses (HRSVs). Generally, patients infected with HPIVs are treated in outpatient clinics, yet also contribute to ARTI-associated hospitalization in children. Although HPIV infections are well studied in developed countries, these infections remain under-investigated and not considered in the routine laboratory diagnosis of childhood ARTI in many developing countries in Asia. We performed an extensive literature search on the prevalence, epidemiology, and burden of HPIV infections in children less than 5 years in Asia using PubMed and PubMed Central search engines. Based on the literature, the prevalence of HPIV infection in Asia ranges from 1% to 66%. According to many studies, HPIV-3 is the major virus circulating among children; however, several studies failed to detect HPIV-4 due to unavailability of diagnostic tools. In Asian countries, HPIV contributes a substantial disease burden in children. https://www.selleckchem.com/products/lgk-974.html The data in this review should assist researchers and public health authorities to plan preventive measures, including accelerating research on vaccines and antiviral drugs.Biologically plausible computing systems require fine-grain tuning of analog synaptic characteristics. In this study, lithium-doped silicate resistive random access memory with a titanium nitride (TiN) electrode mimicking biological synapses is demonstrated. Biological plausibility of this RRAM device is thought to occur due to the low ionization energy of lithium ions, which enables controllable forming and filamentary retraction spontaneously or under an applied voltage. The TiN electrode can effectively store lithium ions, a principle widely adopted from battery construction, and allows state-dependent decay to be reliably achieved. As a result, this device offers multi-bit functionality and synaptic plasticity for simulating various strengths in neuronal connections. Both short-term memory and long-term memory are emulated across dynamical timescales. Spike-timing-dependent plasticity and paired-pulse facilitation are also demonstrated. These mechanisms are capable of self-pruning to generate efficient neural networks. Time-dependent resistance decay is observed for different conductance values, which mimics both biological and artificial memory pruning and conforms to the trend of the biological brain that prunes weak synaptic connections. By faithfully emulating learning rules that exist in human's higher cortical areas from STDP to synaptic pruning, the device has the capacity to drive forward the development of highly efficient neuromorphic computing systems.Allene oxide synthase (AOS) and hydroperoxide lyase (HPL) are two important members of P450 enzymes metabolizing hydroperoxy fatty acid to produce jasmonates and aldehydes respectively, which function in response to diverse environmental and developmental stimuli. However, their exact roles in soybean have not been clarified. In present study, we identified a lesion-mimic mutant in soybean named NT302, which exhibits etiolated phenotype together with chlorotic and spontaneous lesions on leaves at R3 podding stage. The underlying gene was identified as GmHPL encoding hydroperoxide lyase by map-based cloning strategy. Sequence analysis demonstrated that a single nucleotide mutation created a premature termination codon (Gln20-Ter), which resulted in a truncated GmHPL protein in NT302. GmHPL RNA was significantly reduced in NT302 mutant, while genes in AOS branch of the 13-LOX pathway were up-regulated in NT302. The mutant exhibited higher susceptibility to bacterial leaf pustule (BLP) disease, but increased resistance against common cutworm (CCW) pest. GmHPL was significantly induced in response to MeJA, wounding, and CCW in wild type soybean. Virus induced gene silencing (VIGS) of GhHPL genes gave rise to similar lesion-mimic leaf phenotypes in upland cotton, coupled with upregulation of the expression of JA biosynthesis and JA-induced genes. Our study provides evidence that competition exist between HPL and AOS branches in 13-LOX pathway of the oxylipin metabolism in soybean, thereby plays essential roles in modulation of plant development and defense.Plants harbour highly diverse mycobiomes which sustain essential functions for host health and productivity. However, ecological processes that govern the plant-mycobiome assembly, interactions and their impact on ecosystem functions remain poorly known. Here we characterized the ecological role and community assembly of both abundant and rare fungal taxa along the soil-plant continuums (rhizosphere, phyllosphere and endosphere) in the maize-wheat/barley rotation system under different fertilization practices at two contrasting sites. Our results indicate that mycobiome assembly is shaped predominantly by compartment niche and host species rather than by environmental factors. Moreover, crop-associated fungal communities are dominated by few abundant taxa mainly belonging to Sordariomycetes and Dothideomycetes, while the majority of diversity within mycobiomes are represented by rare taxa. For plant compartments, the abundant sub-community is mainly determined by stochastic processes. In contrast, the rare sub-community is more sensitive to host selection and mainly governed by deterministic processes. Furthermore, our results demonstrate that rare taxa play an important role in fungal co-occurrence network and ecosystem functioning like crop yield and soil enzyme activities. These results significantly advance our understanding of crop mycobiome assembly and highlight the key role of rare taxa in sustaining the stability of crop mycobiomes and ecosystem functions.
Dyspeptic symptoms are not well correlated with gastric emptying (GE) results.
To determine (a) prevalence of delayed SB transit (SBT) in patients undergoing GE scintigraphy for symptoms of gastroparesis; (b) symptoms associated with delayed SBT.
Patients with symptoms of gastroparesis underwent combined GE and SBT scintigraphy (GES/SBTS). Patients ingested a mixed solid (S)-liquid (L) meal with egg whites labeled with 500µCi Tc-99m sulfur colloid and water with 125µCi In-111 DTPA. Retained S and L gastric activity and percent of L In-111 activity in terminal ileum (TI) and/or cecum/colon at 6h were determined. Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) assessed symptoms from 0 (none) to 5 (very severe).
Of 363 patients, 174 (47.9%) had delayed S GE, 141 (38.8%) delayed L GE, and 70 (19.3%) delayed SBT. Delayed SBT was seen in 24 (6.6%) with normal S GE and 46 (12.7%) with delayed S GE. Patients with isolated delayed SBT had highest symptom scores for postprandial fullness (3.5), stomach fullness (3.
Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory tract infections (ARTIs) in children less than 5 years, second only to human respiratory syncytial viruses (HRSVs). Generally, patients infected with HPIVs are treated in outpatient clinics, yet also contribute to ARTI-associated hospitalization in children. Although HPIV infections are well studied in developed countries, these infections remain under-investigated and not considered in the routine laboratory diagnosis of childhood ARTI in many developing countries in Asia. We performed an extensive literature search on the prevalence, epidemiology, and burden of HPIV infections in children less than 5 years in Asia using PubMed and PubMed Central search engines. Based on the literature, the prevalence of HPIV infection in Asia ranges from 1% to 66%. According to many studies, HPIV-3 is the major virus circulating among children; however, several studies failed to detect HPIV-4 due to unavailability of diagnostic tools. In Asian countries, HPIV contributes a substantial disease burden in children. https://www.selleckchem.com/products/lgk-974.html The data in this review should assist researchers and public health authorities to plan preventive measures, including accelerating research on vaccines and antiviral drugs.Biologically plausible computing systems require fine-grain tuning of analog synaptic characteristics. In this study, lithium-doped silicate resistive random access memory with a titanium nitride (TiN) electrode mimicking biological synapses is demonstrated. Biological plausibility of this RRAM device is thought to occur due to the low ionization energy of lithium ions, which enables controllable forming and filamentary retraction spontaneously or under an applied voltage. The TiN electrode can effectively store lithium ions, a principle widely adopted from battery construction, and allows state-dependent decay to be reliably achieved. As a result, this device offers multi-bit functionality and synaptic plasticity for simulating various strengths in neuronal connections. Both short-term memory and long-term memory are emulated across dynamical timescales. Spike-timing-dependent plasticity and paired-pulse facilitation are also demonstrated. These mechanisms are capable of self-pruning to generate efficient neural networks. Time-dependent resistance decay is observed for different conductance values, which mimics both biological and artificial memory pruning and conforms to the trend of the biological brain that prunes weak synaptic connections. By faithfully emulating learning rules that exist in human's higher cortical areas from STDP to synaptic pruning, the device has the capacity to drive forward the development of highly efficient neuromorphic computing systems.Allene oxide synthase (AOS) and hydroperoxide lyase (HPL) are two important members of P450 enzymes metabolizing hydroperoxy fatty acid to produce jasmonates and aldehydes respectively, which function in response to diverse environmental and developmental stimuli. However, their exact roles in soybean have not been clarified. In present study, we identified a lesion-mimic mutant in soybean named NT302, which exhibits etiolated phenotype together with chlorotic and spontaneous lesions on leaves at R3 podding stage. The underlying gene was identified as GmHPL encoding hydroperoxide lyase by map-based cloning strategy. Sequence analysis demonstrated that a single nucleotide mutation created a premature termination codon (Gln20-Ter), which resulted in a truncated GmHPL protein in NT302. GmHPL RNA was significantly reduced in NT302 mutant, while genes in AOS branch of the 13-LOX pathway were up-regulated in NT302. The mutant exhibited higher susceptibility to bacterial leaf pustule (BLP) disease, but increased resistance against common cutworm (CCW) pest. GmHPL was significantly induced in response to MeJA, wounding, and CCW in wild type soybean. Virus induced gene silencing (VIGS) of GhHPL genes gave rise to similar lesion-mimic leaf phenotypes in upland cotton, coupled with upregulation of the expression of JA biosynthesis and JA-induced genes. Our study provides evidence that competition exist between HPL and AOS branches in 13-LOX pathway of the oxylipin metabolism in soybean, thereby plays essential roles in modulation of plant development and defense.Plants harbour highly diverse mycobiomes which sustain essential functions for host health and productivity. However, ecological processes that govern the plant-mycobiome assembly, interactions and their impact on ecosystem functions remain poorly known. Here we characterized the ecological role and community assembly of both abundant and rare fungal taxa along the soil-plant continuums (rhizosphere, phyllosphere and endosphere) in the maize-wheat/barley rotation system under different fertilization practices at two contrasting sites. Our results indicate that mycobiome assembly is shaped predominantly by compartment niche and host species rather than by environmental factors. Moreover, crop-associated fungal communities are dominated by few abundant taxa mainly belonging to Sordariomycetes and Dothideomycetes, while the majority of diversity within mycobiomes are represented by rare taxa. For plant compartments, the abundant sub-community is mainly determined by stochastic processes. In contrast, the rare sub-community is more sensitive to host selection and mainly governed by deterministic processes. Furthermore, our results demonstrate that rare taxa play an important role in fungal co-occurrence network and ecosystem functioning like crop yield and soil enzyme activities. These results significantly advance our understanding of crop mycobiome assembly and highlight the key role of rare taxa in sustaining the stability of crop mycobiomes and ecosystem functions. Dyspeptic symptoms are not well correlated with gastric emptying (GE) results. To determine (a) prevalence of delayed SB transit (SBT) in patients undergoing GE scintigraphy for symptoms of gastroparesis; (b) symptoms associated with delayed SBT. Patients with symptoms of gastroparesis underwent combined GE and SBT scintigraphy (GES/SBTS). Patients ingested a mixed solid (S)-liquid (L) meal with egg whites labeled with 500µCi Tc-99m sulfur colloid and water with 125µCi In-111 DTPA. Retained S and L gastric activity and percent of L In-111 activity in terminal ileum (TI) and/or cecum/colon at 6h were determined. Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) assessed symptoms from 0 (none) to 5 (very severe). Of 363 patients, 174 (47.9%) had delayed S GE, 141 (38.8%) delayed L GE, and 70 (19.3%) delayed SBT. Delayed SBT was seen in 24 (6.6%) with normal S GE and 46 (12.7%) with delayed S GE. Patients with isolated delayed SBT had highest symptom scores for postprandial fullness (3.5), stomach fullness (3.0 Comments 0 Shares 218 Views 0 Reviews -
This paper presents an improved teaching learning-based whale optimization algorithm (TSWOA) used the simplex method. First of all, the combination of WOA algorithm and teaching learning-based algorithm not only achieves a better balance between exploration and exploitation of WOA, but also makes whales have self-learning ability from the biological background, and greatly enriches the theory of the original WOA algorithm. Secondly, the WOA algorithm adds the simplex method to optimize the current worst unit, averting the agents to search at the boundary, and increasing the convergence accuracy and speed of the algorithm. To evaluate the performance of the improved algorithm, the TSWOA algorithm is employed to train the multi-layer perceptron (MLP) neural network. It is a difficult thing to propose a well-pleasing and valid algorithm to optimize the multi-layer perceptron neural network. Fifteen different data sets were selected from the UCI machine learning knowledge and the statistical results were compared with GOA, GSO, SSO, FPA, GA and WOA, severally. The statistical results display that better performance of TSWOA compared to WOA and several well-established algorithms for training multi-layer perceptron neural networks.An outbreak of rapidly spreading coronavirus established human to human transmission and now became a pandemic across the world. The new confirmed cases of infected individuals of COVID-19 are increasing day by day. Therefore, the prediction of infected individuals has become of utmost important for health care arrangements and to control the spread of COVID-19. In this study, we propose a compartmental epidemic model with intervention strategies such as lockdown, quarantine, and hospitalization. We compute the basic reproduction number (R0), which plays a vital role in mathematical epidemiology. Based on R0, it is revealed that the system has two equilibrium, namely disease-free and endemic. We also demonstrate the non-negativity and boundedness of the solutions, local and global stability of equilibria, transcritical bifurcation to analyze its epidemiological relevance. Furthermore, to validate our system, we fit the cumulative and new daily cases in India. We estimate the model parameters and predict the near future scenario of the disease. The global sensitivity analysis has also been performed to observe the impact of different parameters on R0. We also investigate the dynamics of disease in respect of different situations of lockdown, e.g., complete lockdown, partial lockdown, and no lockdown. Our analysis concludes that if there is partial or no lockdown case, then endemic level would be high. Along with this, the high transmission rate ensures higher level of endemicity. From the short time prediction, we predict that India may face a crucial phase (approx 6000000 infected individuals within 140 days) in near future due to COVID-19. Finally, numerical results show that COVID-19 may be controllable by reducing the contacts and increasing the efficacy of lockdown.We explore the local dynamics, flip bifurcation, chaos control and existence of periodic point of the predator-prey model with Allee effect on the prey population in the interior of $\mathbbR^*_+^2$. Nu-merical simulations not only exhibit our results with the theoretical analysis but also show the complex dynamical behaviors, such as the period-2, 8, 11, 17, 20 and 22 orbits. Further, maximum Lyapunov exponents as well as fractal dimensions are also computed numerically to show the presence of chaotic behavior in the model under consideration.In this paper, a stochastic SIRS epidemic model with saturating contact rate is constructed. First, for the deterministic system, the stability of the equilibria is discussed by using eigenvalue theory. Second, for the stochastic system, the threshold conditions of disease extinction and persistence are established. Our results indicate that a large environmental noise intensity can suppress the spread of disease. Conversely, if the intensity of environmental noise is small, the system has a stationary solution which indicates the disease is persistent. Eventually, we introduce some computer simulations to validate the theoretical results.Traditional mathematical models for studying the effects of environmental toxins on population dynamics usually assume that the toxic effects are immediate. However, the effects of toxins on the reproduction and mortality of aquatic populations can be delayed in reality. In this paper, we propose a new mathematical model with delayed toxic responses for aquatic populations in polluted aquatic environments. The delayed model is analyzed in terms of steady states, stability, and bifurcation. The results show that the delayed effect on the reproduction of aquatic populations does not affect the stability of the interior equilibrium, but the delayed effect on the mortality of aquatic populations can destabilize the interior equilibrium. Numerical results corroborate the theoretical ones are presented.This study revises the non-local macroscopic pedestrian flow model proposed in [R. M. Colombo, M. Garavello, and M. Lécureux-Mercier. A class of nonlocal models for pedestrian traffic. Math. Models Methods Appl. Sci., 22(4)1150023, 2012] to account for anisotropic interactions and the presence of walls or other obstacles in the walking domain. We prove the well-posedness of this extended model and we apply high-resolution numerical schemes to illustrate the model characteristics. In particular, numerical simulations highlight the role of different model parameters in the observed pattern formation.The high sampling frequency of traditional Nyquist sampling theory not only puts greater requirements on the sampling equipment, but also generates a large amount of data, which increases the difficulty of information transmission and storage. To this end, this paper proposes a rolling bearing fault signal detection method based on compressed sensing combined with a neural network. Based on the theory of compressed sensing, the observations obtained from compression sampling are divided into two sets of data. Given the one set of data, the predictive ability of the nonlinear time series through the neural network can predict the second set of observed values. https://www.selleckchem.com/products/nvp-bsk805.html The predicted observations are used to reconstruct the signal, thereby reducing the amount of data to be stored and transmitted and realizing secondary compression of the signal.
This paper presents an improved teaching learning-based whale optimization algorithm (TSWOA) used the simplex method. First of all, the combination of WOA algorithm and teaching learning-based algorithm not only achieves a better balance between exploration and exploitation of WOA, but also makes whales have self-learning ability from the biological background, and greatly enriches the theory of the original WOA algorithm. Secondly, the WOA algorithm adds the simplex method to optimize the current worst unit, averting the agents to search at the boundary, and increasing the convergence accuracy and speed of the algorithm. To evaluate the performance of the improved algorithm, the TSWOA algorithm is employed to train the multi-layer perceptron (MLP) neural network. It is a difficult thing to propose a well-pleasing and valid algorithm to optimize the multi-layer perceptron neural network. Fifteen different data sets were selected from the UCI machine learning knowledge and the statistical results were compared with GOA, GSO, SSO, FPA, GA and WOA, severally. The statistical results display that better performance of TSWOA compared to WOA and several well-established algorithms for training multi-layer perceptron neural networks.An outbreak of rapidly spreading coronavirus established human to human transmission and now became a pandemic across the world. The new confirmed cases of infected individuals of COVID-19 are increasing day by day. Therefore, the prediction of infected individuals has become of utmost important for health care arrangements and to control the spread of COVID-19. In this study, we propose a compartmental epidemic model with intervention strategies such as lockdown, quarantine, and hospitalization. We compute the basic reproduction number (R0), which plays a vital role in mathematical epidemiology. Based on R0, it is revealed that the system has two equilibrium, namely disease-free and endemic. We also demonstrate the non-negativity and boundedness of the solutions, local and global stability of equilibria, transcritical bifurcation to analyze its epidemiological relevance. Furthermore, to validate our system, we fit the cumulative and new daily cases in India. We estimate the model parameters and predict the near future scenario of the disease. The global sensitivity analysis has also been performed to observe the impact of different parameters on R0. We also investigate the dynamics of disease in respect of different situations of lockdown, e.g., complete lockdown, partial lockdown, and no lockdown. Our analysis concludes that if there is partial or no lockdown case, then endemic level would be high. Along with this, the high transmission rate ensures higher level of endemicity. From the short time prediction, we predict that India may face a crucial phase (approx 6000000 infected individuals within 140 days) in near future due to COVID-19. Finally, numerical results show that COVID-19 may be controllable by reducing the contacts and increasing the efficacy of lockdown.We explore the local dynamics, flip bifurcation, chaos control and existence of periodic point of the predator-prey model with Allee effect on the prey population in the interior of $\mathbbR^*_+^2$. Nu-merical simulations not only exhibit our results with the theoretical analysis but also show the complex dynamical behaviors, such as the period-2, 8, 11, 17, 20 and 22 orbits. Further, maximum Lyapunov exponents as well as fractal dimensions are also computed numerically to show the presence of chaotic behavior in the model under consideration.In this paper, a stochastic SIRS epidemic model with saturating contact rate is constructed. First, for the deterministic system, the stability of the equilibria is discussed by using eigenvalue theory. Second, for the stochastic system, the threshold conditions of disease extinction and persistence are established. Our results indicate that a large environmental noise intensity can suppress the spread of disease. Conversely, if the intensity of environmental noise is small, the system has a stationary solution which indicates the disease is persistent. Eventually, we introduce some computer simulations to validate the theoretical results.Traditional mathematical models for studying the effects of environmental toxins on population dynamics usually assume that the toxic effects are immediate. However, the effects of toxins on the reproduction and mortality of aquatic populations can be delayed in reality. In this paper, we propose a new mathematical model with delayed toxic responses for aquatic populations in polluted aquatic environments. The delayed model is analyzed in terms of steady states, stability, and bifurcation. The results show that the delayed effect on the reproduction of aquatic populations does not affect the stability of the interior equilibrium, but the delayed effect on the mortality of aquatic populations can destabilize the interior equilibrium. Numerical results corroborate the theoretical ones are presented.This study revises the non-local macroscopic pedestrian flow model proposed in [R. M. Colombo, M. Garavello, and M. Lécureux-Mercier. A class of nonlocal models for pedestrian traffic. Math. Models Methods Appl. Sci., 22(4)1150023, 2012] to account for anisotropic interactions and the presence of walls or other obstacles in the walking domain. We prove the well-posedness of this extended model and we apply high-resolution numerical schemes to illustrate the model characteristics. In particular, numerical simulations highlight the role of different model parameters in the observed pattern formation.The high sampling frequency of traditional Nyquist sampling theory not only puts greater requirements on the sampling equipment, but also generates a large amount of data, which increases the difficulty of information transmission and storage. To this end, this paper proposes a rolling bearing fault signal detection method based on compressed sensing combined with a neural network. Based on the theory of compressed sensing, the observations obtained from compression sampling are divided into two sets of data. Given the one set of data, the predictive ability of the nonlinear time series through the neural network can predict the second set of observed values. https://www.selleckchem.com/products/nvp-bsk805.html The predicted observations are used to reconstruct the signal, thereby reducing the amount of data to be stored and transmitted and realizing secondary compression of the signal.0 Comments 0 Shares 207 Views 0 Reviews -
Clinacanthus nutans (C. nutans) Lind. locally known as Belalai Gajah or Sabah snake grass is a medicinal plant belonging to Acanthaceae family. In Asia, this plant is traditionally used for treating skin rashes, insects and snake bites, diabetes mellitus, fever and for diuretic effect. C. nutans has been reported to possess biological activities including anti-oxidant, anti-inflammation, anti-cancer, anti-diabetic and anti-viral activities.
Proton Nuclear Magnetic Resonance (
H NMR) and Liquid Chromatography Mass Spectroscopy (LCMS) coupled with multivariate data analysis were employed to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media in rat renal proximal tubular cells (NRK-52E).
NMR and LCMS analysis highlighted choline, creatine, phosphocholine, valine, acetic acid, phenylalanine, leucine, glutamic acid, threonine, uridine and proline as the main metabolites which differentiated the cisplatin-induced group of NRK-52E from control cells extract. https://www.selleckchem.com/products/leukadherin-1.html The corresponding media exhibited lactic acid, glutamine, glutamic acid and glucose-1-phosphate as the varied metabolites. The altered pathways perturbed by cisplatin nephrotoxic on NRK-52E cells included changes in amino acid metabolism, lipid metabolism and glycolysis.
The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group.
The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group.
Excisional haemorrhoidectomy is the gold standard technique in patients with III and IV degree haemorrhoidal disease (HD). However, it is associated with a significant rate of post-operative pain. The aim of our study was to evaluate the efficacy of mesoglycan in the post-operative period of patients who underwent open excisional diathermy haemorrhoidectomy (OEH).
This was a retrospective multicentre observational study. Three hundred ninety-eight patients from sixteen colorectal referral centres who underwent OEH for III and IV HD were enrolled. All patients were followed-up on the first post-operative day (T1) and after 1week (T2), 3weeks (T3) and 6weeks (T4). BMI, habits, SF-12 questionnaire, VAS at rest (VASs), after defecation (VASd), and after anorectal digital examination (VASe), bleeding and thrombosis, time to surgical wound healing and autonomy were evaluated.
In the mesoglycan group, post-operative thrombosis was significantly reduced at T2 (p < 0.05) and T3 (p < 0.005), and all patientO) https//clinicaltrials.gov/ct2/show/NCT04481698?term=Mesoglycan+for+Pain+Control+After+Open+Excisional+HAEMOrrhoidectomy+%28MeHAEMO%29&draw=2&rank=1.
The aim of the present study was to examine the influence of body mass index category, as well as of demographic and socioeconomic factors on the participation in organized physical activity (OPA) of schoolchildren attending primary and secondary school in Greece. Furthermore, to compare the difference between the two levels.
This is a cross-sectional study conducted on a representative elementary and secondary school cohort, derived using stratification and probability proportional to size (PPS) methodology. The final sample included 18,264 subjects, aged 6 to 15 years. Parents of all students and students of secondary schools fulfilled validated questionnaires evaluating socioeconomic status, and participation to OPA. International Obesity Task Force (IOTF) cut offs were used to classify the children. Univariate and multivariate logistic models examined factors associated with OPA. All analyses were stratified by school level.
Sport participation was not reported in 37.7 and 54.4% of primary and seconm should be tailored to the specific needs of different weight categories and can possibly eliminate the impact of SES inequalities.
Since the time of declaration of global pandemic of COVID-19 by World Health Organization (WHO), falsified hand sanitizers surfaced regularly in markets, posing possible harm to public due to unlisted inclusion of methanol. The current research is an attempt to develop and validate a tool to document falsified hand sanitizer in the UAE community.
A descriptive cross-sectional community-based study was conducted among 1280 randomly selected participants. Respondents were sent a web-based electronic link to the survey via email. Content validity, factor analyses and known group validity were used to develop and validate a new scale to identify falsified hand sanitizer. Test-retest reliability, internal consistency, item internal consistency (IIC), and intraclass correlation coefficients (ICCs) were used to assess the reliability of the scale. SPSS version 24 was used to conduct data analysis.
A total of 1280 participants were enrolled in the study. The content validity index (CVI) was 0.83 with the final ticipants with post-graduate education were more likely to identify the falsified hand sanitizer compared to those with high school education. (p < 0.001).
This study developed and validated a new scale for the measurement of falsified hand sanitizer. This is expected to improve and promote collaboration between the health regulators and the public and hereby encourage customer satisfaction and participation.
This study developed and validated a new scale for the measurement of falsified hand sanitizer. This is expected to improve and promote collaboration between the health regulators and the public and hereby encourage customer satisfaction and participation.
For improved outcomes in total knee arthroplasty (TKA) correct implant fitting and positioning are crucial. In order to facilitate a best possible implant fitting and positioning patient-specific systems have been developed. However, whether or not these systems allow for better implant fitting and positioning has yet to be elucidated. For this reason, the aim was to analyse the novel patient-specific cruciate retaining knee replacement system iTotal™ CR G2 that utilizes custom-made implants and instruments for its ability to facilitate accurate implant fitting and positioning including correction of the hip-knee-ankle angle (HKA).
We assessed radiographic results of 106 patients who were treated with the second generation of a patient-specific cruciate retaining knee arthroplasty using iTotal™ CR G2 (ConforMIS Inc.) for tricompartmental knee osteoarthritis (OA) using custom-made implants and instruments. The implant fit and positioning as well as the correction of the mechanical axis (hip-knee-ankle angle, HKA) and restoration of the joint line were determined using pre- and postoperative radiographic analyses.
Clinacanthus nutans (C. nutans) Lind. locally known as Belalai Gajah or Sabah snake grass is a medicinal plant belonging to Acanthaceae family. In Asia, this plant is traditionally used for treating skin rashes, insects and snake bites, diabetes mellitus, fever and for diuretic effect. C. nutans has been reported to possess biological activities including anti-oxidant, anti-inflammation, anti-cancer, anti-diabetic and anti-viral activities. Proton Nuclear Magnetic Resonance ( H NMR) and Liquid Chromatography Mass Spectroscopy (LCMS) coupled with multivariate data analysis were employed to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media in rat renal proximal tubular cells (NRK-52E). NMR and LCMS analysis highlighted choline, creatine, phosphocholine, valine, acetic acid, phenylalanine, leucine, glutamic acid, threonine, uridine and proline as the main metabolites which differentiated the cisplatin-induced group of NRK-52E from control cells extract. https://www.selleckchem.com/products/leukadherin-1.html The corresponding media exhibited lactic acid, glutamine, glutamic acid and glucose-1-phosphate as the varied metabolites. The altered pathways perturbed by cisplatin nephrotoxic on NRK-52E cells included changes in amino acid metabolism, lipid metabolism and glycolysis. The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group. The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group. Excisional haemorrhoidectomy is the gold standard technique in patients with III and IV degree haemorrhoidal disease (HD). However, it is associated with a significant rate of post-operative pain. The aim of our study was to evaluate the efficacy of mesoglycan in the post-operative period of patients who underwent open excisional diathermy haemorrhoidectomy (OEH). This was a retrospective multicentre observational study. Three hundred ninety-eight patients from sixteen colorectal referral centres who underwent OEH for III and IV HD were enrolled. All patients were followed-up on the first post-operative day (T1) and after 1week (T2), 3weeks (T3) and 6weeks (T4). BMI, habits, SF-12 questionnaire, VAS at rest (VASs), after defecation (VASd), and after anorectal digital examination (VASe), bleeding and thrombosis, time to surgical wound healing and autonomy were evaluated. In the mesoglycan group, post-operative thrombosis was significantly reduced at T2 (p < 0.05) and T3 (p < 0.005), and all patientO) https//clinicaltrials.gov/ct2/show/NCT04481698?term=Mesoglycan+for+Pain+Control+After+Open+Excisional+HAEMOrrhoidectomy+%28MeHAEMO%29&draw=2&rank=1. The aim of the present study was to examine the influence of body mass index category, as well as of demographic and socioeconomic factors on the participation in organized physical activity (OPA) of schoolchildren attending primary and secondary school in Greece. Furthermore, to compare the difference between the two levels. This is a cross-sectional study conducted on a representative elementary and secondary school cohort, derived using stratification and probability proportional to size (PPS) methodology. The final sample included 18,264 subjects, aged 6 to 15 years. Parents of all students and students of secondary schools fulfilled validated questionnaires evaluating socioeconomic status, and participation to OPA. International Obesity Task Force (IOTF) cut offs were used to classify the children. Univariate and multivariate logistic models examined factors associated with OPA. All analyses were stratified by school level. Sport participation was not reported in 37.7 and 54.4% of primary and seconm should be tailored to the specific needs of different weight categories and can possibly eliminate the impact of SES inequalities. Since the time of declaration of global pandemic of COVID-19 by World Health Organization (WHO), falsified hand sanitizers surfaced regularly in markets, posing possible harm to public due to unlisted inclusion of methanol. The current research is an attempt to develop and validate a tool to document falsified hand sanitizer in the UAE community. A descriptive cross-sectional community-based study was conducted among 1280 randomly selected participants. Respondents were sent a web-based electronic link to the survey via email. Content validity, factor analyses and known group validity were used to develop and validate a new scale to identify falsified hand sanitizer. Test-retest reliability, internal consistency, item internal consistency (IIC), and intraclass correlation coefficients (ICCs) were used to assess the reliability of the scale. SPSS version 24 was used to conduct data analysis. A total of 1280 participants were enrolled in the study. The content validity index (CVI) was 0.83 with the final ticipants with post-graduate education were more likely to identify the falsified hand sanitizer compared to those with high school education. (p < 0.001). This study developed and validated a new scale for the measurement of falsified hand sanitizer. This is expected to improve and promote collaboration between the health regulators and the public and hereby encourage customer satisfaction and participation. This study developed and validated a new scale for the measurement of falsified hand sanitizer. This is expected to improve and promote collaboration between the health regulators and the public and hereby encourage customer satisfaction and participation. For improved outcomes in total knee arthroplasty (TKA) correct implant fitting and positioning are crucial. In order to facilitate a best possible implant fitting and positioning patient-specific systems have been developed. However, whether or not these systems allow for better implant fitting and positioning has yet to be elucidated. For this reason, the aim was to analyse the novel patient-specific cruciate retaining knee replacement system iTotal™ CR G2 that utilizes custom-made implants and instruments for its ability to facilitate accurate implant fitting and positioning including correction of the hip-knee-ankle angle (HKA). We assessed radiographic results of 106 patients who were treated with the second generation of a patient-specific cruciate retaining knee arthroplasty using iTotal™ CR G2 (ConforMIS Inc.) for tricompartmental knee osteoarthritis (OA) using custom-made implants and instruments. The implant fit and positioning as well as the correction of the mechanical axis (hip-knee-ankle angle, HKA) and restoration of the joint line were determined using pre- and postoperative radiographic analyses.0 Comments 0 Shares 170 Views 0 Reviews -
The expression of PD-L1 could be a novel biomarker which predicts that patients are more likely to respond to immunotherapy. Our study investigated the relationship among clinicopathological characteristics, prognosis, PD-L1 expression levels, and FOXP3+ Treg infiltration. In addition, the relationship among clinicopathological characteristics, prognosis, PD-L1 expression levels, and FOXP3+ Treg infiltration was explored. Furthermore, the relationship between PD-L1 expression and FOXP3+ Treg infiltration was examined. We found that 41.3% of pancreatic cancer patients had PD-L1-positive staining; both PD-L1 expression levels and FOXP3+ Treg infiltration were significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and pTNM. In addition, PD-L1 expression and FOXP3+ Treg infiltration also could be prognostic biomarkers for pancreatic cancer.The prognostic value of microvessel density (MVD) in head and neck squamous cell carcinoma (HNSCC) remains disputable. The purpose of this study was to comprehensively determine the prognostic value of MVD in HNSCC. Relevant literatures were identified using PubMed, Embase, and Cochrane Library. A meta-analysis was performed to clarify the prognostic role of MVD in HNSCC patients and different subgroups. A total of 14 eligible articles were included in this meta-analysis. The combined hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival (OS) of 11 studies was 1.663 (1.236-2.237, P = 0.001), and the pooled HR and 95% CI for progression-free survival (PFS) of 7 studies was 2.069 (1.281-3.343, P = 0.003). Subgroup analyses were also performed on different issues, such as regional distribution of patients, age, tumor location, antibody, and treatment strategy. To conclude, high MVD is associated with worse OS and PFS in patients with HNSCC.
Obstructive sleep apnea (OSA) was highly prevalent in patients with type 2 diabetes (T2D). Cathepsin S (CTSS), a cysteine protease, is involved in the inflammatory activity in T2D and hypoxia conditions. The aim of the study was to evaluate whether CTSS could be involved in the inflammatory reaction of OSA in patients with T2D.
We included 158 participants in this study matched for age, gender, and body mass index in 4 groups (control, non-OSA&T2D, OSA&non-T2D, and OSA&T2D). After overnight polysomnography, we collected the clinical data including anthropometrical characteristics, blood pressure, and fasting blood samples in the morning. Plasma CTSS concentration was evaluated using the human Magnetic Luminex Assay.
Compared with the control group, both the non-OSA&T2D group and the OSA&non-T2D group showed higher CTSS levels. Plasma CTSS expression was significantly increased in subjects with OSA&T2D compared to subjects with non-OSA&T2D. The OSA&T2D group had higher CTSS levels than the OSA&non-T2D group, but there were no statistically significant differences. Plasma CTSS levels showed significant correlation with the apnea-hypopnea index (AHI) (
= 0.559,
< 0.001) and plasma fasting blood glucose (
= 0.427,
< 0.001). After adjusting confounding factors, plasma CTSS levels were independently associated with the AHI (Beta 0.386, 95% confidence intervals (CI) 21.988 to 57.781;
< 0.001). Furthermore, we confirmed the higher pinpoint accuracy of plasma CTSS in the diagnosis of OSA (area under the curve 0.868).
Plasma CTSS expression was significantly elevated in the OSA&T2D group and was independently associated with the AHI; it could be a biomarker with a positive diagnostic value on diagnosing OSA among patients with T2D.
Plasma CTSS expression was significantly elevated in the OSA&T2D group and was independently associated with the AHI; it could be a biomarker with a positive diagnostic value on diagnosing OSA among patients with T2D.[This corrects the article DOI 10.1155/2015/190405.].
Spinal cord injuries (SCIs) induce secondary neuroinflammation through astrocyte reactivation, which adversely affects neuronal survival and eventually causes long-term disability. CDGSH iron sulfur domain 2 (CISD2), which has been reported to be involved in mediating the anti-inflammatory responses, can serve as a target in SCI therapy. Wild bitter melon (WBM;
Linn. var. abbreviata Ser.) contains an anti-inflammatory agent called alpha-eleostearic acid (
-ESA), a peroxisome proliferator-activated receptor-
(PPAR-
) ligand. Activated PPAR-
inhibits the nuclear factor
B (NF-
B) signaling pathway via the inhibition of I
B (inhibitor of NF-
B) degradation. https://www.selleckchem.com/products/AT7867.html The role of astrocyte deactivation and CISD2 in anti-inflammatory mechanisms of WBM in acute SCIs is unknown.
A mouse model of SCI was generated via spinal cord hemisection. The SCI **** were administered WBM intraperitoneally (500 mg/kg bodyweight). Lipopolysaccharide- (LPS-) stimulated ALT cells (astrocytes) were used as an
model for stuignaling pathway in neural cells, and that WBM can mitigate the injury-induced downregulation of CISD2 in SCI **** and LPS-stimulated ALT astrocytes.
Our aim was to evaluate the effect of adalimumab on work productivity measures, overall activity impairment, and sleep quality in patients with active moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) treated in routine care settings in Greece and determine factors associated with work impairment and sleep disturbance.
Patients with active moderate to severe RA (
= 184), PsA (
= 166), and AS (
= 150) were enrolled in this 24-month, prospective, observational study at 80 hospital outpatient clinics and private practices throughout Greece. Patients received adalimumab alone or in combination with standard antirheumatic therapies according to routine care. Work productivity and sleep were assessed through two patient-reported outcome measures the Work Productivity and Activity Impairment-General Health questionnaire and the Medical Outcomes Study Sleep Scale (MOS-SS). Pearson correlation coefficients were estimated to assess the association of work impairment and sleep disturbances with disease activity scores.
The expression of PD-L1 could be a novel biomarker which predicts that patients are more likely to respond to immunotherapy. Our study investigated the relationship among clinicopathological characteristics, prognosis, PD-L1 expression levels, and FOXP3+ Treg infiltration. In addition, the relationship among clinicopathological characteristics, prognosis, PD-L1 expression levels, and FOXP3+ Treg infiltration was explored. Furthermore, the relationship between PD-L1 expression and FOXP3+ Treg infiltration was examined. We found that 41.3% of pancreatic cancer patients had PD-L1-positive staining; both PD-L1 expression levels and FOXP3+ Treg infiltration were significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and pTNM. In addition, PD-L1 expression and FOXP3+ Treg infiltration also could be prognostic biomarkers for pancreatic cancer.The prognostic value of microvessel density (MVD) in head and neck squamous cell carcinoma (HNSCC) remains disputable. The purpose of this study was to comprehensively determine the prognostic value of MVD in HNSCC. Relevant literatures were identified using PubMed, Embase, and Cochrane Library. A meta-analysis was performed to clarify the prognostic role of MVD in HNSCC patients and different subgroups. A total of 14 eligible articles were included in this meta-analysis. The combined hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival (OS) of 11 studies was 1.663 (1.236-2.237, P = 0.001), and the pooled HR and 95% CI for progression-free survival (PFS) of 7 studies was 2.069 (1.281-3.343, P = 0.003). Subgroup analyses were also performed on different issues, such as regional distribution of patients, age, tumor location, antibody, and treatment strategy. To conclude, high MVD is associated with worse OS and PFS in patients with HNSCC. Obstructive sleep apnea (OSA) was highly prevalent in patients with type 2 diabetes (T2D). Cathepsin S (CTSS), a cysteine protease, is involved in the inflammatory activity in T2D and hypoxia conditions. The aim of the study was to evaluate whether CTSS could be involved in the inflammatory reaction of OSA in patients with T2D. We included 158 participants in this study matched for age, gender, and body mass index in 4 groups (control, non-OSA&T2D, OSA&non-T2D, and OSA&T2D). After overnight polysomnography, we collected the clinical data including anthropometrical characteristics, blood pressure, and fasting blood samples in the morning. Plasma CTSS concentration was evaluated using the human Magnetic Luminex Assay. Compared with the control group, both the non-OSA&T2D group and the OSA&non-T2D group showed higher CTSS levels. Plasma CTSS expression was significantly increased in subjects with OSA&T2D compared to subjects with non-OSA&T2D. The OSA&T2D group had higher CTSS levels than the OSA&non-T2D group, but there were no statistically significant differences. Plasma CTSS levels showed significant correlation with the apnea-hypopnea index (AHI) ( = 0.559, < 0.001) and plasma fasting blood glucose ( = 0.427, < 0.001). After adjusting confounding factors, plasma CTSS levels were independently associated with the AHI (Beta 0.386, 95% confidence intervals (CI) 21.988 to 57.781; < 0.001). Furthermore, we confirmed the higher pinpoint accuracy of plasma CTSS in the diagnosis of OSA (area under the curve 0.868). Plasma CTSS expression was significantly elevated in the OSA&T2D group and was independently associated with the AHI; it could be a biomarker with a positive diagnostic value on diagnosing OSA among patients with T2D. Plasma CTSS expression was significantly elevated in the OSA&T2D group and was independently associated with the AHI; it could be a biomarker with a positive diagnostic value on diagnosing OSA among patients with T2D.[This corrects the article DOI 10.1155/2015/190405.]. Spinal cord injuries (SCIs) induce secondary neuroinflammation through astrocyte reactivation, which adversely affects neuronal survival and eventually causes long-term disability. CDGSH iron sulfur domain 2 (CISD2), which has been reported to be involved in mediating the anti-inflammatory responses, can serve as a target in SCI therapy. Wild bitter melon (WBM; Linn. var. abbreviata Ser.) contains an anti-inflammatory agent called alpha-eleostearic acid ( -ESA), a peroxisome proliferator-activated receptor- (PPAR- ) ligand. Activated PPAR- inhibits the nuclear factor B (NF- B) signaling pathway via the inhibition of I B (inhibitor of NF- B) degradation. https://www.selleckchem.com/products/AT7867.html The role of astrocyte deactivation and CISD2 in anti-inflammatory mechanisms of WBM in acute SCIs is unknown. A mouse model of SCI was generated via spinal cord hemisection. The SCI mice were administered WBM intraperitoneally (500 mg/kg bodyweight). Lipopolysaccharide- (LPS-) stimulated ALT cells (astrocytes) were used as an model for stuignaling pathway in neural cells, and that WBM can mitigate the injury-induced downregulation of CISD2 in SCI mice and LPS-stimulated ALT astrocytes. Our aim was to evaluate the effect of adalimumab on work productivity measures, overall activity impairment, and sleep quality in patients with active moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) treated in routine care settings in Greece and determine factors associated with work impairment and sleep disturbance. Patients with active moderate to severe RA ( = 184), PsA ( = 166), and AS ( = 150) were enrolled in this 24-month, prospective, observational study at 80 hospital outpatient clinics and private practices throughout Greece. Patients received adalimumab alone or in combination with standard antirheumatic therapies according to routine care. Work productivity and sleep were assessed through two patient-reported outcome measures the Work Productivity and Activity Impairment-General Health questionnaire and the Medical Outcomes Study Sleep Scale (MOS-SS). Pearson correlation coefficients were estimated to assess the association of work impairment and sleep disturbances with disease activity scores.0 Comments 0 Shares 223 Views 0 Reviews -
oxygen species and the subsequent stress response have been linked to the development of inflammation and progression toward the more severe forms of the disease. Here, we demonstrate that DENV uses the NS2B3 protease complex to strategically target Nrf2 for degradation, leading to a progressive increase in oxidative stress, inflammation, and cell death in infected cells. This study underlines the pivotal role of the Nrf2 regulatory network in the context of DENV infection.Chikungunya virus (CHIKV) is a mosquito-borne alphavirus associated with debilitating arthralgia in humans. RNA secondary structure in the viral genome plays an important role in the lifecycle of alphaviruses; however, the specific role of RNA structure in regulating CHIKV replication is poorly understood. Our previous studies found little conservation in RNA secondary structure between alphaviruses, and this structural divergence creates unique functional structures in specific alphavirus genomes. Therefore, to understand the impact of RNA structure on CHIKV biology, we used SHAPE-MaP to inform the modeling of RNA secondary structure throughout the genome of a CHIKV isolate from the 2013 Caribbean outbreak. We then analyzed regions of the genome with high levels of structural specificity to identify potentially functional RNA secondary structures and identified 23 regions within the CHIKV genome with higher than average structural stability, including four previously identified, functionally important CHIKV es have only been defined for a small portion of the CHIKV genome, we used a chemical probing method to define the RNA secondary structures of CHIKV genomic RNA. We identified 23 highly specific structured regions of the genome, and confirmed the functional importance of one structure using mutagenesis. Furthermore, we defined the RNA secondary structure of three CHIKV 3'UTR variants that differ in their ability to replicate in mosquito cells. Our study highlights the complexity of the CHIKV genome and describes new systems for designing compensatory mutations to test the functional relevance of viral RNA secondary structures.The contribution of T cell and antibody responses following vaccination in resistance to herpes simplex virus 1 (HSV-1) infection continues to be rigorously investigated. In the present article, we explore the contribution of CD8+ T cells specific for the major antigenic epitope for HSV-1 glycoprotein B (gB498-505, gB) in C57BL/6 **** using a transgenic mouse (gBT-I.1) model vaccinated with HSV-1 0ΔNLS. gBT-I.1-vaccinated **** did not generate a robust neutralization antibody titer in comparison to the HSV-1 0ΔNLS-vaccinated wild-type C57BL/6 counterpart. https://www.selleckchem.com/products/7acc2.html Nevertheless, the vaccinated gBT-I.1 **** were resistant to ocular challenge with HSV-1 compared to vehicle-vaccinated animals based on survival and reduced corneal neovascularization but displayed similar levels of corneal opacity. Whereas there was no difference in the virus titer recovered from the cornea comparing vaccinated ****, HSV-1 0ΔNLS-vaccinated animals possessed significantly less infectious virus during acute infection in the trigeminal gangliaus 1 (HSV-1) 0ΔNLS vaccine, the correlate of protection has been defined to be primarily antibody driven. The current study shows that in the near absence of anti-HSV-1 antibody, vaccinated **** are protected from subsequent challenge with wild-type HSV-1 as measured by survival. The efficacy is lost following depletion of CD8+ T cells. Whereas increased survival and reduction in virus replication were observed in vaccinated **** challenged with HSV-1, cornea pathology was mixed with a reduction in neovascularization but no change in opacity. Collectively, the study suggests CD8+ T cells significantly contribute to the host adaptive immune response to HSV-1 challenge following vaccination with an attenuated virus, but multiple factors are involved in cornea pathology in response to ocular virus challenge.Viruses have colonized the germ line of our ancestors on several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few nonretroviruses. Among the recently emerged viruses infecting humans, several target the testis (e.g., human immunodeficiency virus [HIV], Zika virus, and Ebola virus). Here, we aimed to investigate whether human testicular germ cells (TGCs) can support integration by HIV, a contemporary retrovirus that started to spread in the human population during the last century. We report that albeit alternative receptors enabled HIV-1 binding to TGCs, HIV virions failed to infect TGCs in vitro Nevertheless, exposure of TGCs to infected lymphocytes, naturally present in the testis from HIV+ men, led to HIV-1 entry, integration, and early protein expression. Similarly, cell-associated infection or bypassing viral entry led to HIV-1 integration in a spermatogonial cell line. Using DNAscope, HIV-1 and simian immunodeficiency irion binding but not entry. However, HIV-1 entered and integrated into TGCs upon cell-associated infection and produced low levels of viral proteins. In vivo, HIV-1 and SIV DNA was detected in a few TGCs. Molecular landscape analysis showed that TGCs have overall weak antiviral defenses. Altogether, our results indicate that human TGCs can support HIV-1 early replication, including integration, suggesting potential for endogenization in future generations.
Evaluate if the coronavirus disease 2019 (COVID-19) pandemic influences parents' intentions to have their children receive the 2020-2021 seasonal influenza vaccination.
In May 2020, we recruited 2164 US parents and guardians of children ages 6 months to 5 years to complete a brief online survey that examined parental behavior and decision-making in response to experimental stimuli and real-world events. We estimated a multivariate multinomial logistic regression (controlling for key demographics) to assess the relationship between a child's 2019-2020 influenza vaccination status and the COVID-19 pandemic's influence on a parent's intentions for their child's 2020-2021 influenza vaccination.
Changes in vaccination intentions significantly differed between parents whose children received the 2019-2020 influenza vaccine compared with those whose children did not (
< .001). Specifically, among parents whose children did not receive the 2019-2020 vaccine, 34% (95% confidence interval [CI] 30%-37%) reported that the COVID-19 pandemic made them less likely to have their child receive the 2020-2021 vaccine.
oxygen species and the subsequent stress response have been linked to the development of inflammation and progression toward the more severe forms of the disease. Here, we demonstrate that DENV uses the NS2B3 protease complex to strategically target Nrf2 for degradation, leading to a progressive increase in oxidative stress, inflammation, and cell death in infected cells. This study underlines the pivotal role of the Nrf2 regulatory network in the context of DENV infection.Chikungunya virus (CHIKV) is a mosquito-borne alphavirus associated with debilitating arthralgia in humans. RNA secondary structure in the viral genome plays an important role in the lifecycle of alphaviruses; however, the specific role of RNA structure in regulating CHIKV replication is poorly understood. Our previous studies found little conservation in RNA secondary structure between alphaviruses, and this structural divergence creates unique functional structures in specific alphavirus genomes. Therefore, to understand the impact of RNA structure on CHIKV biology, we used SHAPE-MaP to inform the modeling of RNA secondary structure throughout the genome of a CHIKV isolate from the 2013 Caribbean outbreak. We then analyzed regions of the genome with high levels of structural specificity to identify potentially functional RNA secondary structures and identified 23 regions within the CHIKV genome with higher than average structural stability, including four previously identified, functionally important CHIKV es have only been defined for a small portion of the CHIKV genome, we used a chemical probing method to define the RNA secondary structures of CHIKV genomic RNA. We identified 23 highly specific structured regions of the genome, and confirmed the functional importance of one structure using mutagenesis. Furthermore, we defined the RNA secondary structure of three CHIKV 3'UTR variants that differ in their ability to replicate in mosquito cells. Our study highlights the complexity of the CHIKV genome and describes new systems for designing compensatory mutations to test the functional relevance of viral RNA secondary structures.The contribution of T cell and antibody responses following vaccination in resistance to herpes simplex virus 1 (HSV-1) infection continues to be rigorously investigated. In the present article, we explore the contribution of CD8+ T cells specific for the major antigenic epitope for HSV-1 glycoprotein B (gB498-505, gB) in C57BL/6 mice using a transgenic mouse (gBT-I.1) model vaccinated with HSV-1 0ΔNLS. gBT-I.1-vaccinated mice did not generate a robust neutralization antibody titer in comparison to the HSV-1 0ΔNLS-vaccinated wild-type C57BL/6 counterpart. https://www.selleckchem.com/products/7acc2.html Nevertheless, the vaccinated gBT-I.1 mice were resistant to ocular challenge with HSV-1 compared to vehicle-vaccinated animals based on survival and reduced corneal neovascularization but displayed similar levels of corneal opacity. Whereas there was no difference in the virus titer recovered from the cornea comparing vaccinated mice, HSV-1 0ΔNLS-vaccinated animals possessed significantly less infectious virus during acute infection in the trigeminal gangliaus 1 (HSV-1) 0ΔNLS vaccine, the correlate of protection has been defined to be primarily antibody driven. The current study shows that in the near absence of anti-HSV-1 antibody, vaccinated mice are protected from subsequent challenge with wild-type HSV-1 as measured by survival. The efficacy is lost following depletion of CD8+ T cells. Whereas increased survival and reduction in virus replication were observed in vaccinated mice challenged with HSV-1, cornea pathology was mixed with a reduction in neovascularization but no change in opacity. Collectively, the study suggests CD8+ T cells significantly contribute to the host adaptive immune response to HSV-1 challenge following vaccination with an attenuated virus, but multiple factors are involved in cornea pathology in response to ocular virus challenge.Viruses have colonized the germ line of our ancestors on several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few nonretroviruses. Among the recently emerged viruses infecting humans, several target the testis (e.g., human immunodeficiency virus [HIV], Zika virus, and Ebola virus). Here, we aimed to investigate whether human testicular germ cells (TGCs) can support integration by HIV, a contemporary retrovirus that started to spread in the human population during the last century. We report that albeit alternative receptors enabled HIV-1 binding to TGCs, HIV virions failed to infect TGCs in vitro Nevertheless, exposure of TGCs to infected lymphocytes, naturally present in the testis from HIV+ men, led to HIV-1 entry, integration, and early protein expression. Similarly, cell-associated infection or bypassing viral entry led to HIV-1 integration in a spermatogonial cell line. Using DNAscope, HIV-1 and simian immunodeficiency irion binding but not entry. However, HIV-1 entered and integrated into TGCs upon cell-associated infection and produced low levels of viral proteins. In vivo, HIV-1 and SIV DNA was detected in a few TGCs. Molecular landscape analysis showed that TGCs have overall weak antiviral defenses. Altogether, our results indicate that human TGCs can support HIV-1 early replication, including integration, suggesting potential for endogenization in future generations. Evaluate if the coronavirus disease 2019 (COVID-19) pandemic influences parents' intentions to have their children receive the 2020-2021 seasonal influenza vaccination. In May 2020, we recruited 2164 US parents and guardians of children ages 6 months to 5 years to complete a brief online survey that examined parental behavior and decision-making in response to experimental stimuli and real-world events. We estimated a multivariate multinomial logistic regression (controlling for key demographics) to assess the relationship between a child's 2019-2020 influenza vaccination status and the COVID-19 pandemic's influence on a parent's intentions for their child's 2020-2021 influenza vaccination. Changes in vaccination intentions significantly differed between parents whose children received the 2019-2020 influenza vaccine compared with those whose children did not ( < .001). Specifically, among parents whose children did not receive the 2019-2020 vaccine, 34% (95% confidence interval [CI] 30%-37%) reported that the COVID-19 pandemic made them less likely to have their child receive the 2020-2021 vaccine.0 Comments 0 Shares 175 Views 0 Reviews -
Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. https://www.selleckchem.com/products/ddr1-in-1.html Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected ****. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host-pathogen interaction.Translocation of proteins across biological membranes is essential for life. Proteins that clog the endoplasmic reticulum (ER) translocon prevent the movement of other proteins into the ER. Eukaryotes have multiple translocon quality control (TQC) mechanisms to detect and destroy proteins that persistently engage the translocon. TQC mechanisms have been defined using a limited panel of substrates that aberrantly occupy the channel. The extent of substrate overlap among TQC pathways is unknown. In this study, we found that two TQC enzymes, the ER-associated degradation ubiquitin ligase Hrd1 and zinc metalloprotease Ste24, promote degradation of characterized translocon-associated substrates of the other enzyme in Saccharomyces cerevisiae Although both enzymes contribute to substrate turnover, our results suggest a prominent role for Hrd1 in TQC. Yeast lacking both Hrd1 and Ste24 exhibit a profound growth defect, consistent with overlapping function. Remarkably, two mutations that mildly perturb post-translational translocation and reduce the extent of aberrant translocon engagement by a model substrate diminish cellular dependence on TQC enzymes. Our data reveal previously unappreciated mechanistic complexity in TQC substrate detection and suggest that a robust translocon surveillance infrastructure maintains functional and efficient translocation machinery.
To assess the relation of type 2 diabetes occurring earlier (age <55 years) versus later in life to the risk of cardiovascular death and to diabetes in offspring.
In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5,571 first- and second-generation participants with mortality data and 2,123 second-generation participants who initially did not have diabetes with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death)-control (noncardiovascular death) design and incident diabetes in offspring in relation to parental early-onset diabetes.
Among the participants in two generations (
= 5,571), there were 1,822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus noncardiovascular death increased with decreasing age of diabetes onset (
< 0.001 trend). Compared with never developing diabetes, early-onset diabetes conferred a 1.81-fold odds (95% CI 1.10-2.97,
= 0.02) of cardiovascular death and 1.75-fold odds (0.96-3.21,
= 0.07) of coronary death, whereas later-onset diabetes was not associated with greater risk for either (
= 0.09 for cardiovascular death;
= 0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73-6.07), whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50-3.19).
Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.
Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission.
The treatment of infective endocarditis (IE) has become more complex with the current myriad healthcare-associated factors and the regional differences in causative organisms. We aimed to investigate the overall trends, microbiological features, and outcomes of IE in South Korea.
A 12-year retrospective cohort study was performed. Poisson regression was used to estimate the time trends of IE incidence and mortality rate. Risk factors for in-hospital mortality were identified with multivariable logistic regression, and model comparison was performed to evaluate the predictive performance of notable risk factors. Kaplan-Meier survival analysis and Cox regression were performed to assess long-term prognosis.
We included 419 patients with IE, the incidence of which showed an increasing trend (relative risk 1.06, p=0.005), whereas mortality demonstrated a decreasing trend (incidence rate ratio 0.93, p=0.020). The in-hospital mortality rate was 14.6%. On multivariable logistic regression analysis, aortic valve endocarditis (OR 3.18, p=0.001), IE caused by
(OR 2.32, p=0.026), neurological complications (OR 1.98, p=0.031), high Sequential Organ Failure Assessment score (OR 1.22, p=0.023) and high Charlson Comorbidity Index (OR 1.11, p=0.019) were predictors of in-hospital mortality. Surgical intervention for IE was a protective factor against in-hospital mortality (OR 0.25, p<0.001) and was associated with improved long-term prognosis compared with medical treatment only (p<0.001).
The incidence of IE is increasing in South Korea. Although the mortality rate has slightly decreased, it remains high. Surgery has a protective effect with respect to both in-hospital mortality and long-term prognosis in patients with IE.
The incidence of IE is increasing in South Korea. Although the mortality rate has slightly decreased, it remains high. Surgery has a protective effect with respect to both in-hospital mortality and long-term prognosis in patients with IE.
Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. https://www.selleckchem.com/products/ddr1-in-1.html Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host-pathogen interaction.Translocation of proteins across biological membranes is essential for life. Proteins that clog the endoplasmic reticulum (ER) translocon prevent the movement of other proteins into the ER. Eukaryotes have multiple translocon quality control (TQC) mechanisms to detect and destroy proteins that persistently engage the translocon. TQC mechanisms have been defined using a limited panel of substrates that aberrantly occupy the channel. The extent of substrate overlap among TQC pathways is unknown. In this study, we found that two TQC enzymes, the ER-associated degradation ubiquitin ligase Hrd1 and zinc metalloprotease Ste24, promote degradation of characterized translocon-associated substrates of the other enzyme in Saccharomyces cerevisiae Although both enzymes contribute to substrate turnover, our results suggest a prominent role for Hrd1 in TQC. Yeast lacking both Hrd1 and Ste24 exhibit a profound growth defect, consistent with overlapping function. Remarkably, two mutations that mildly perturb post-translational translocation and reduce the extent of aberrant translocon engagement by a model substrate diminish cellular dependence on TQC enzymes. Our data reveal previously unappreciated mechanistic complexity in TQC substrate detection and suggest that a robust translocon surveillance infrastructure maintains functional and efficient translocation machinery. To assess the relation of type 2 diabetes occurring earlier (age <55 years) versus later in life to the risk of cardiovascular death and to diabetes in offspring. In the Framingham Heart Study, a community-based prospective cohort study, glycemic status was ascertained at serial examinations over six decades among 5,571 first- and second-generation participants with mortality data and 2,123 second-generation participants who initially did not have diabetes with data on parental diabetes status. We assessed cause of death in a case (cardiovascular death)-control (noncardiovascular death) design and incident diabetes in offspring in relation to parental early-onset diabetes. Among the participants in two generations ( = 5,571), there were 1,822 cardiovascular deaths (including 961 coronary deaths). The odds of cardiovascular versus noncardiovascular death increased with decreasing age of diabetes onset ( < 0.001 trend). Compared with never developing diabetes, early-onset diabetes conferred a 1.81-fold odds (95% CI 1.10-2.97, = 0.02) of cardiovascular death and 1.75-fold odds (0.96-3.21, = 0.07) of coronary death, whereas later-onset diabetes was not associated with greater risk for either ( = 0.09 for cardiovascular death; = 0.51 for coronary death). In second-generation participants, having a parent with early-onset diabetes increased diabetes risk by 3.24-fold (1.73-6.07), whereas having one or both parents with late-onset diabetes increased diabetes risk by 2.19-fold (1.50-3.19). Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission. Our findings provide evidence for a diabetes subgroup with an early onset, a stronger association with cardiovascular death, and higher transgenerational transmission. The treatment of infective endocarditis (IE) has become more complex with the current myriad healthcare-associated factors and the regional differences in causative organisms. We aimed to investigate the overall trends, microbiological features, and outcomes of IE in South Korea. A 12-year retrospective cohort study was performed. Poisson regression was used to estimate the time trends of IE incidence and mortality rate. Risk factors for in-hospital mortality were identified with multivariable logistic regression, and model comparison was performed to evaluate the predictive performance of notable risk factors. Kaplan-Meier survival analysis and Cox regression were performed to assess long-term prognosis. We included 419 patients with IE, the incidence of which showed an increasing trend (relative risk 1.06, p=0.005), whereas mortality demonstrated a decreasing trend (incidence rate ratio 0.93, p=0.020). The in-hospital mortality rate was 14.6%. On multivariable logistic regression analysis, aortic valve endocarditis (OR 3.18, p=0.001), IE caused by (OR 2.32, p=0.026), neurological complications (OR 1.98, p=0.031), high Sequential Organ Failure Assessment score (OR 1.22, p=0.023) and high Charlson Comorbidity Index (OR 1.11, p=0.019) were predictors of in-hospital mortality. Surgical intervention for IE was a protective factor against in-hospital mortality (OR 0.25, p<0.001) and was associated with improved long-term prognosis compared with medical treatment only (p<0.001). The incidence of IE is increasing in South Korea. Although the mortality rate has slightly decreased, it remains high. Surgery has a protective effect with respect to both in-hospital mortality and long-term prognosis in patients with IE. The incidence of IE is increasing in South Korea. Although the mortality rate has slightly decreased, it remains high. Surgery has a protective effect with respect to both in-hospital mortality and long-term prognosis in patients with IE.0 Comments 0 Shares 164 Views 0 Reviews -
Neuroinflammation and periphery-to-CNS neuroimmune cross-talk in patients with painful knee osteoarthritis (OA) are poorly understood. We utilized proximity extension assay to measure the level of 91 inflammatory proteins in CSF and serum from OA patients and controls. The patients had elevated levels of 48 proteins in CSF indicating neuroinflammation. Ten proteins were correlated between CSF and serum and potentially involved in periphery-to-CNS neuroimmune cross-talk. Seven CSF proteins, all with previously reported neuroprotective effects, were associated with lower pain intensity and milder knee-related symptoms. Our findings indicate that neuroinflammation in OA could be protective and associated with less severe symptoms.Primary cell culture in vitro suffers from cellular senescence. We hypothesized that expansion on decellularized extracellular matrix (dECM) deposited by simian virus 40 large T antigen (SV40LT) transduced autologous infrapatellar fat pad stem cells (IPFSCs) could rejuvenate high-passage IPFSCs in both proliferation and chondrogenic differentiation. In the study, we found that SV40LT transduced IPFSCs exhibited increased proliferation and adipogenic potential but decreased chondrogenic potential. Expansion on dECMs deposited by passage 5 IPFSCs yielded IPFSCs with dramatically increased proliferation and chondrogenic differentiation capacity; however, this enhanced capacity diminished if IPFSCs were grown on dECM deposited by passage 15 IPFSCs. Interestingly, expansion on dECM deposited by SV40LT transduced IPFSCs yielded IPFSCs with enhanced proliferation and chondrogenic capacity but decreased adipogenic potential, particularly for the dECM group derived from SV40LT transduced passage 15 cells. Our immunofluorescence staining and proteomics data identify matrix components such as basement membrane proteins as top candidates for matrix mediated IPFSC rejuvenation. Both cell proliferation and differentiation were endorsed by transcripts measured by RNASeq during the process. This study provides a promising model for in-depth investigation of the matrix protein influence on surrounding stem cell differentiation.A variety of targeted nanoparticles were developed for the diagnosis and therapy of orthotopic and metastatic bone tumors during the past decade. This critical review will focus on principles and methods in the design of these bone-targeted nanoparticles. Ligands including bisphosphonates, aspartic acid-rich peptides and synthetic polymers were grafted on nanoparticles such as PLGA nanoparticles, liposomes, dendrimers and inorganic nanoparticles for bone targeting. Besides, other ligands such as monoclonal antibodies, peptides and aptamers targeting biomarkers on tumor/bone cells were identified for targeted diagnosis and therapy. Examples of targeted nanoparticles for the early detection of bone metastatic tumors and the ablation of cancer via chemotherapy, photothermal therapy, gene therapy and combination therapy will be intensively reviewed. The development of multifunctional nanoparticles to break down the "vicious" cycle between tumor cell proliferation and bone resorption, and the challenges and perspectives in this area will be discussed.Liver tissue engineering offers a promising strategy for liver failure patients. Since transplantation rejection resulting in vessel thrombosis is regarded as a major hurdle, vascular reconstruction is one of indispensable requirements of whole organ engineering. Here we demonstrated a novel strategy for reconstruction of a vascularized bioengineered human liver (VBHL) using decellularized liver scaffolds in an efficient manner. First we achieved fully functional endothelial coverage of scaffolds by adopting the anti-CD31 aptamer as a potent coating agent for re-endothelialization. Through an ex vivo human blood perfusion that recapitulates the blood coagulation response in humans, we demonstrated significantly reduced platelet aggregation in anti-CD31 aptamer coated scaffolds. We then produced VBHL constructs using liver parenchymal cells and nonparenchymal cells, properly organized into liver-like structures with an aligned vasculature. Interestingly, VBHL constructs displayed prominently enhanced long-term liver-specific functions that are affected by vascular functionality. The VBHL constructs formed perfusable vessel networks in vivo as evidenced by the direct vascular connection between the VBHL constructs and the renal circulation. Furthermore, heterotopic transplantation of VBHL constructs supported liver functions in a rat model of liver fibrosis. Overall, we proposed a new strategy to generate transplantable bioengineered livers characterized by highly functional vascular reconstruction.A lysosomal-targeted near infrared (NIR) fluorescent probe for reactive oxygen species (ROS) was developed with highly sensitive ability. The different responding activity toward H2O2, OH, and HClO were investigated. Meanwhile, the probe has been successfully applied in detecting and imaging reactive oxygen species both in cells and in vivo.In this work, a novel phenoxazine-based fluorescent probe BPO-N3 was developed to detect H2S. https://www.selleckchem.com/products/nvp-tnks656.html The results showed that the probe had high selectivity and sensitivity toward H2S, and its detection mechanism was based the ratio between green and red fluorescence signals; its detection limit was as low as 30 nM. The fluorescent imaging experiments further showed that the probe BPO-N3 could successfully detect endogenous and exogenous H2S in living cells. This probe can be used as a powerful tool for in-depth study of H2S function in various physiological processes.In this work, a painting suspected of counterfeiting was analyzed using the synchrotron-based scanning macro X-ray fluorescence (MA-XRF) technique. The canvas has erasures including a signature erasure; however, some visible numbers indicate that the artwork may be from the 17th century. Through the studies' elemental maps, Cl-K and Ca-K were observed, which allowed us to reconstruct the signature present in the painting. Elemental maps of Ba-K, Ti-K, Fe-K, Zn-K, and Pb-K were also obtained from the painting, which made possible to visualize how the pigments based on these elements were used in the creative composition of the painting. In addition to the signature region, a region of the painting with dimensions of approximately 120 mm × 120 mm was investigated by synchrotron radiation induced MA-XRF, while keeping a high spatial resolution and elemental sensitivity. The measurements were carried out at the D09B micro-XRF beamline of the Brazilian Synchrotron Light Laboratory (LNLS), part of the Brazilian Center of Research in Energy and Materials, in Campinas Brazil.
Neuroinflammation and periphery-to-CNS neuroimmune cross-talk in patients with painful knee osteoarthritis (OA) are poorly understood. We utilized proximity extension assay to measure the level of 91 inflammatory proteins in CSF and serum from OA patients and controls. The patients had elevated levels of 48 proteins in CSF indicating neuroinflammation. Ten proteins were correlated between CSF and serum and potentially involved in periphery-to-CNS neuroimmune cross-talk. Seven CSF proteins, all with previously reported neuroprotective effects, were associated with lower pain intensity and milder knee-related symptoms. Our findings indicate that neuroinflammation in OA could be protective and associated with less severe symptoms.Primary cell culture in vitro suffers from cellular senescence. We hypothesized that expansion on decellularized extracellular matrix (dECM) deposited by simian virus 40 large T antigen (SV40LT) transduced autologous infrapatellar fat pad stem cells (IPFSCs) could rejuvenate high-passage IPFSCs in both proliferation and chondrogenic differentiation. In the study, we found that SV40LT transduced IPFSCs exhibited increased proliferation and adipogenic potential but decreased chondrogenic potential. Expansion on dECMs deposited by passage 5 IPFSCs yielded IPFSCs with dramatically increased proliferation and chondrogenic differentiation capacity; however, this enhanced capacity diminished if IPFSCs were grown on dECM deposited by passage 15 IPFSCs. Interestingly, expansion on dECM deposited by SV40LT transduced IPFSCs yielded IPFSCs with enhanced proliferation and chondrogenic capacity but decreased adipogenic potential, particularly for the dECM group derived from SV40LT transduced passage 15 cells. Our immunofluorescence staining and proteomics data identify matrix components such as basement membrane proteins as top candidates for matrix mediated IPFSC rejuvenation. Both cell proliferation and differentiation were endorsed by transcripts measured by RNASeq during the process. This study provides a promising model for in-depth investigation of the matrix protein influence on surrounding stem cell differentiation.A variety of targeted nanoparticles were developed for the diagnosis and therapy of orthotopic and metastatic bone tumors during the past decade. This critical review will focus on principles and methods in the design of these bone-targeted nanoparticles. Ligands including bisphosphonates, aspartic acid-rich peptides and synthetic polymers were grafted on nanoparticles such as PLGA nanoparticles, liposomes, dendrimers and inorganic nanoparticles for bone targeting. Besides, other ligands such as monoclonal antibodies, peptides and aptamers targeting biomarkers on tumor/bone cells were identified for targeted diagnosis and therapy. Examples of targeted nanoparticles for the early detection of bone metastatic tumors and the ablation of cancer via chemotherapy, photothermal therapy, gene therapy and combination therapy will be intensively reviewed. The development of multifunctional nanoparticles to break down the "vicious" cycle between tumor cell proliferation and bone resorption, and the challenges and perspectives in this area will be discussed.Liver tissue engineering offers a promising strategy for liver failure patients. Since transplantation rejection resulting in vessel thrombosis is regarded as a major hurdle, vascular reconstruction is one of indispensable requirements of whole organ engineering. Here we demonstrated a novel strategy for reconstruction of a vascularized bioengineered human liver (VBHL) using decellularized liver scaffolds in an efficient manner. First we achieved fully functional endothelial coverage of scaffolds by adopting the anti-CD31 aptamer as a potent coating agent for re-endothelialization. Through an ex vivo human blood perfusion that recapitulates the blood coagulation response in humans, we demonstrated significantly reduced platelet aggregation in anti-CD31 aptamer coated scaffolds. We then produced VBHL constructs using liver parenchymal cells and nonparenchymal cells, properly organized into liver-like structures with an aligned vasculature. Interestingly, VBHL constructs displayed prominently enhanced long-term liver-specific functions that are affected by vascular functionality. The VBHL constructs formed perfusable vessel networks in vivo as evidenced by the direct vascular connection between the VBHL constructs and the renal circulation. Furthermore, heterotopic transplantation of VBHL constructs supported liver functions in a rat model of liver fibrosis. Overall, we proposed a new strategy to generate transplantable bioengineered livers characterized by highly functional vascular reconstruction.A lysosomal-targeted near infrared (NIR) fluorescent probe for reactive oxygen species (ROS) was developed with highly sensitive ability. The different responding activity toward H2O2, OH, and HClO were investigated. Meanwhile, the probe has been successfully applied in detecting and imaging reactive oxygen species both in cells and in vivo.In this work, a novel phenoxazine-based fluorescent probe BPO-N3 was developed to detect H2S. https://www.selleckchem.com/products/nvp-tnks656.html The results showed that the probe had high selectivity and sensitivity toward H2S, and its detection mechanism was based the ratio between green and red fluorescence signals; its detection limit was as low as 30 nM. The fluorescent imaging experiments further showed that the probe BPO-N3 could successfully detect endogenous and exogenous H2S in living cells. This probe can be used as a powerful tool for in-depth study of H2S function in various physiological processes.In this work, a painting suspected of counterfeiting was analyzed using the synchrotron-based scanning macro X-ray fluorescence (MA-XRF) technique. The canvas has erasures including a signature erasure; however, some visible numbers indicate that the artwork may be from the 17th century. Through the studies' elemental maps, Cl-K and Ca-K were observed, which allowed us to reconstruct the signature present in the painting. Elemental maps of Ba-K, Ti-K, Fe-K, Zn-K, and Pb-K were also obtained from the painting, which made possible to visualize how the pigments based on these elements were used in the creative composition of the painting. In addition to the signature region, a region of the painting with dimensions of approximately 120 mm × 120 mm was investigated by synchrotron radiation induced MA-XRF, while keeping a high spatial resolution and elemental sensitivity. The measurements were carried out at the D09B micro-XRF beamline of the Brazilian Synchrotron Light Laboratory (LNLS), part of the Brazilian Center of Research in Energy and Materials, in Campinas Brazil.0 Comments 0 Shares 22 Views 0 Reviews -
This study utilizes the Theory of Planned Behavior (TPB) variables-including "attitude," "subjective norms," and "perceived behavioral control"-to understand the relationship between mask-wearing behavior and physical/non-physical leisure activity participation in Koreans as well as the tendencies behind mask-wearing intentions within leisure activities. The measurement tools used attitude, subjective norms, control, and mask use intention factors based on the TPB. Overall, 545 individuals participated, and the non-overlapping regions, sex, and age were considered through the stratified sampling method. The survey was conducted online owing to COVID-19, and collected data were derived through descriptive and multiple linear regression analyses. First, a difference in mask-wearing intention based on physical and non-physical leisure activities was identified; second, attitudes and perceived behaviors were considered in light of the dangers posed by COVID-19. It was found that control influences the tendency of intention to wear a mask depending on whether the group was engaged in physical or non-physical activity. Therefore, it can be stated that mask-wearing must be mandatory during physical and non-physical activities owing to respiratory diseases such as COVID-19. It is also important to simultaneously promote a positive attitude toward mask-wearing to enable people to believe that they can stay in full control of their own health.Metformin, one of the most frequently prescribed oral anti-diabetic drugs, is characterized by multidirectional activity, including lipid lowering, cardio-protective and anti-inflammatory properties. This study presents synthesis and stability studies of 10 novel sulfonamide-based derivatives of metformin with alkyl substituents in the aromatic ring. The potential of the synthesized compounds as glucose-lowering agents and their effects on selected parameters of plasma and vascular hemostasis were examined. Compounds with two or three methyl groups in the aromatic ring (6, 7, 9, 10) significantly increased glucose uptake in human umbilical vein endothelial cells (HUVECs), e.g., 15.8 µmol/L for comp. 6 at 0.3 µmol/mL versus 11.4 ± 0.7 µmol/L for control. Basic coagulation studies showed that all examined compounds inhibit intrinsic coagulation pathway and the process of fibrin polymerization stronger than the parent drug, metformin, which give evidence of their greater anti-coagulant properties. Importantly, synthesized compounds decrease the activity of factor X, a first member of common coagulation pathway, while metformin does not affect coagulation factor X (FX) activity. A multiparametric clot formation and lysis test (CL-test) revealed that the examined compounds significantly prolong the onset of clot formation; however, they do not affect the overall potential of clot formation and fibrinolysis. Erythrotoxicity studies confirmed that none of the synthesized compounds exert an adverse effect on erythrocyte integrity, do not contribute to the massive hemolysis and do not interact strongly with the erythrocyte membrane. https://www.selleckchem.com/ In summary, chemical modification of metformin scaffold into benzenesulfonamides containing alkyl substituents leads to the formation of potential dual-action agents with comparable glucose-lowering properties and stronger anti-coagulant activity than the parent drug, metformin.Steatosis is characterized by excessive triglycerides accumulation in liver cells. Recently, application of herbal formulations has gained importance in treating complex diseases. Therefore, this study explores the efficacy of tri-herbal medicine Divya Sarva-Kalp-Kwath (SKK; brand name, Livogrit) in treating free fatty acid (FFA)-induced steatosis in human liver (HepG2) cells and rat primary hepatocytes. Previously, we demonstrated that cytosafe SKK ameliorated CCl4-induced hepatotoxicity. In this study, we evaluated the role of SKK in reducing FFA-induced cell-death, and steatosis in HepG2 through analysis of cell viability, intracellular lipid and triglyceride accumulation, extracellular free glycerol levels, and mRNA expression changes. Plant metabolic components fingerprinting in SKK was performed via High Performance Thin Layer Chromatography (HPTLC). Treatment with SKK significantly reduced the loss of cell viability induced by 2 mM-FFA in a dose-dependent manner. SKK also reduced intracellular lipid, triglyceride accumulation, secreted AST levels, and increased extracellular free glycerol presence in the FFA-exposed cells. SKK normalized the FFA-stimulated overexpression of SREBP1c, FAS, C/EBPα, and CPT1A genes associated with the induction of steatosis. In addition, treatment of rat primary hepatocytes with FFA and SKK concurrently, reduced intracellular lipid accumulation. Thus, SKK showed efficacy in reducing intracellular triglyceride accumulation and increasing extracellular glycerol release, along with downregulation of related key genetic factors for FFA-associated steatosis.Previous histories of animal experimentation, e.g., Franco (2013) have focused on ethics, the law and the personalities involved, but not on the involvement of anaesthetics or analgesics. Given that these were major subjects of (UK) Parliamentary debates on vivisection in the mid-19th century and viewed as "indisputable refinements in animal experimentation" (Russell and Burch 1959), it seemed that an analysis of their role was overdue. This commentary has, in interweaving the history of animal experimentation in the UK with the evolution of anaesthesia, attempted to (1) clarify the evidence for Russell and Burch's view; and (2) evaluate anaesthesia's ongoing contribution to experimental refinement. The history that emerges reveals that the withholding or misuse of anaesthetics and, or analgesics from laboratory animals in the UK has had a profound effect on scientists and indirectly on the attitudes of the British public in general, becoming a major driver for the establishment of the anti-vivisection movemecome an unavoidable consideration whenever animal experiments are planned and conducted. This has been accompanied by a proliferation of training and educational programmes in laboratory animal anaesthesia.
This study utilizes the Theory of Planned Behavior (TPB) variables-including "attitude," "subjective norms," and "perceived behavioral control"-to understand the relationship between mask-wearing behavior and physical/non-physical leisure activity participation in Koreans as well as the tendencies behind mask-wearing intentions within leisure activities. The measurement tools used attitude, subjective norms, control, and mask use intention factors based on the TPB. Overall, 545 individuals participated, and the non-overlapping regions, sex, and age were considered through the stratified sampling method. The survey was conducted online owing to COVID-19, and collected data were derived through descriptive and multiple linear regression analyses. First, a difference in mask-wearing intention based on physical and non-physical leisure activities was identified; second, attitudes and perceived behaviors were considered in light of the dangers posed by COVID-19. It was found that control influences the tendency of intention to wear a mask depending on whether the group was engaged in physical or non-physical activity. Therefore, it can be stated that mask-wearing must be mandatory during physical and non-physical activities owing to respiratory diseases such as COVID-19. It is also important to simultaneously promote a positive attitude toward mask-wearing to enable people to believe that they can stay in full control of their own health.Metformin, one of the most frequently prescribed oral anti-diabetic drugs, is characterized by multidirectional activity, including lipid lowering, cardio-protective and anti-inflammatory properties. This study presents synthesis and stability studies of 10 novel sulfonamide-based derivatives of metformin with alkyl substituents in the aromatic ring. The potential of the synthesized compounds as glucose-lowering agents and their effects on selected parameters of plasma and vascular hemostasis were examined. Compounds with two or three methyl groups in the aromatic ring (6, 7, 9, 10) significantly increased glucose uptake in human umbilical vein endothelial cells (HUVECs), e.g., 15.8 µmol/L for comp. 6 at 0.3 µmol/mL versus 11.4 ± 0.7 µmol/L for control. Basic coagulation studies showed that all examined compounds inhibit intrinsic coagulation pathway and the process of fibrin polymerization stronger than the parent drug, metformin, which give evidence of their greater anti-coagulant properties. Importantly, synthesized compounds decrease the activity of factor X, a first member of common coagulation pathway, while metformin does not affect coagulation factor X (FX) activity. A multiparametric clot formation and lysis test (CL-test) revealed that the examined compounds significantly prolong the onset of clot formation; however, they do not affect the overall potential of clot formation and fibrinolysis. Erythrotoxicity studies confirmed that none of the synthesized compounds exert an adverse effect on erythrocyte integrity, do not contribute to the massive hemolysis and do not interact strongly with the erythrocyte membrane. https://www.selleckchem.com/ In summary, chemical modification of metformin scaffold into benzenesulfonamides containing alkyl substituents leads to the formation of potential dual-action agents with comparable glucose-lowering properties and stronger anti-coagulant activity than the parent drug, metformin.Steatosis is characterized by excessive triglycerides accumulation in liver cells. Recently, application of herbal formulations has gained importance in treating complex diseases. Therefore, this study explores the efficacy of tri-herbal medicine Divya Sarva-Kalp-Kwath (SKK; brand name, Livogrit) in treating free fatty acid (FFA)-induced steatosis in human liver (HepG2) cells and rat primary hepatocytes. Previously, we demonstrated that cytosafe SKK ameliorated CCl4-induced hepatotoxicity. In this study, we evaluated the role of SKK in reducing FFA-induced cell-death, and steatosis in HepG2 through analysis of cell viability, intracellular lipid and triglyceride accumulation, extracellular free glycerol levels, and mRNA expression changes. Plant metabolic components fingerprinting in SKK was performed via High Performance Thin Layer Chromatography (HPTLC). Treatment with SKK significantly reduced the loss of cell viability induced by 2 mM-FFA in a dose-dependent manner. SKK also reduced intracellular lipid, triglyceride accumulation, secreted AST levels, and increased extracellular free glycerol presence in the FFA-exposed cells. SKK normalized the FFA-stimulated overexpression of SREBP1c, FAS, C/EBPα, and CPT1A genes associated with the induction of steatosis. In addition, treatment of rat primary hepatocytes with FFA and SKK concurrently, reduced intracellular lipid accumulation. Thus, SKK showed efficacy in reducing intracellular triglyceride accumulation and increasing extracellular glycerol release, along with downregulation of related key genetic factors for FFA-associated steatosis.Previous histories of animal experimentation, e.g., Franco (2013) have focused on ethics, the law and the personalities involved, but not on the involvement of anaesthetics or analgesics. Given that these were major subjects of (UK) Parliamentary debates on vivisection in the mid-19th century and viewed as "indisputable refinements in animal experimentation" (Russell and Burch 1959), it seemed that an analysis of their role was overdue. This commentary has, in interweaving the history of animal experimentation in the UK with the evolution of anaesthesia, attempted to (1) clarify the evidence for Russell and Burch's view; and (2) evaluate anaesthesia's ongoing contribution to experimental refinement. The history that emerges reveals that the withholding or misuse of anaesthetics and, or analgesics from laboratory animals in the UK has had a profound effect on scientists and indirectly on the attitudes of the British public in general, becoming a major driver for the establishment of the anti-vivisection movemecome an unavoidable consideration whenever animal experiments are planned and conducted. This has been accompanied by a proliferation of training and educational programmes in laboratory animal anaesthesia.0 Comments 0 Shares 23 Views 0 Reviews -
Intervention effects were assessed by mixed analysis of variance. Somatic, psychological, and urogenital symptoms were immediately alleviated after the marine healing program. No effect of sea mustard was detected in the marine group. After 2 weeks, the effect of marine healing persisted in physical and mental exhaustion only. A 5-day integrated marine healing program, but not additional sea mustard intake, temporarily alleviated menopausal symptoms. The reduction in physical and mental exhaustion after marine healing can be maintained for 2 weeks. Trial Registration Clinical Research Information Service Identifier KCT0004025. Mumps is contagious disease and maintaining immunity to mumps in healthcare worker (HCW) is important for preventing transmission in the hospital. We evaluated the seroprevalence of mumps in HCWs in a tertiary care hospital in Republic of Korea. A total of 6,055 HCWs born between 1950 and 1995 underwent antibody testing. The overall seropositivity rate of mumps was 87% (95% confidence interval, 86%-87%). Our data indicates that, in Korean HCWs, testing for mumps antibody followed by mumps vaccination is more appropriate than routine mumps vaccination without testing for mumps antibody. © Korean Vaccine Society.Purpose When influenza viruses are cultured in eggs, amino acid mutations of the hemagglutinin may occur through egg adaptation. On the other hand, when influenza viruses are cultured in animal cells, no antigenic mutation occurs unlike in eggs. Therefore, we examined whether the antigenic mutations actually occurred after passage of H3N2 (A/Texas/50/2012) virus up to 15 times in eggs and ****-Sky3851 cells. Materials and Methods Prototype A/Texas/50/2012 (H3N2) influenza virus which was isolated from clinical patient, not passaged in egg, was obtained and propagated using the specific pathogen free egg and the ****-Sky3851 cell line up to 15 passage, and the changes in the antigen sequence of the influenza viruses were confirmed by gene sequencing and protein structure analysis. Results In term of the hemagglutination titer of influenza virus, the reactivity to chicken and guinea pig red blood cell showed different results between egg propagated and cell propagated viruses. In the sequence analysis results for hemagglutinin and neuraminidase, no antigenic mutation was observed throughout all passages when cultured in ****-Sky3851 cells. On the other hand, mutations occurred in three amino acid sequences (H156R, G186S, S219F) in hemagglutinin up to 15 passages when cultured in eggs. Conclusion H3N2 influenza virus cultured in eggs could lead mutations in amino acid sequence of hemagglutinin, distinct from the corresponding virus cultured in cells for which no antigenic mutation was observed. These findings suggest that cell culture is a more stable and effective way of production with lower risk of antigenic mutations for the manufacture of influenza vaccines. © Korean Vaccine Society.Purpose Most cell culture processes for viral vaccine production are mainly based on adherent cell culture systems using serum, which are associated with expensive and labor-intensive processes to produce large amounts of viral vaccine strains. In this study, we investigated whether Vero cells could be grown in serum-free and shaking suspension conditions. Furthermore, we assessed the ability of the Vero cell suspension culture system to produce adenovirus type 5 (Ad5), compared to that of the adhesive Vero cell culture system. Materials and Methods We tested the feasibility of commercial serum-free media for Vero cell culture. For the adaptation of Vero cells in suspension culture, adhesive Vero cells were added in the early phase of shaking suspension culture, and 50 days after shaking suspension culture, suspension-adapted Vero cells were subcultured continuously. To assess the virus production ability of Vero cells in suspension, the cells were infected with Ad5-green fluorescent protein and evaluated based on their fluorescence intensity. Results The Vero cells grown in OptiPRO serum-free medium showed no changes in morphology and growth rate, but ****5 and FRhk-4 cells showed morphological changes and decreased growth rate, respectively. The Vero cells were well adapted to the suspension culture system. The Vero cells in suspension showed a better Ad5 production ability than the adherent Vero cells. Conclusion Vero cells can be grown in OptiPRO serum-free medium. Further, our suspension culture-adapted Vero cells may be suitable to produce viral vaccine strains due to their high ability to produce viruses such as Ad5. © Korean Vaccine Society.Purpose We constructed a new canine adenovirus type 2 (CAV-2) vaccine candidate using the recently isolated Korean CAV-2 strain; we termed the vaccine APQA1701-40P and evaluated its safety and immunogenicity in dogs. Materials and Methods To generate the anti-CAV-2 vaccine, APQA1701 was passaged 40 times in **** cells growing in medium containing 5 mM urea and the virus was inactivated using 0.05% (volume per volume) formaldehyde. Two vaccines were prepared by blending inactivated APQA1701-40P with two different adjuvants; both were intramuscularly injected (twice) into guinea pigs. The safety and immunogenicity of the Cabopol-adjuvanted vaccine were evaluated in seronegative dogs. The humoral responses elicited were measured using an indirect enzyme-linked immunosorbent assay (I-ELISA), and via a virus neutralization assay (VNA). https://www.selleckchem.com/products/gossypol.html Results The new, inactivated CAV-2 vaccine strain, APQA1701-40P, lacked six amino acids of the E1b-19K protein. In guinea pigs, the Cabopol-adjuvanted vaccine afforded a slightly higher VNA titer and I-ELISA absorbance than an IMS gel-adjuvanted vaccine 4 weeks post-vaccination (p>0.05). Dogs inoculated with the former vaccine developed a significantly higher immune titer than non-vaccinated dogs. Conclusion The Cabopol-adjuvanted, inactivated CAV-2 vaccine was safe and induced a high VNA titer in dogs. © Korean Vaccine Society.Purpose To date, many kinds of classical ***** fever (CSF) vaccines have been developed to protect against this disease. However, the efficacy of these vaccines to protect the pig against field CSF strains needs to be considered, based on circulating strains of classical ***** fever virus (CSFV). Materials and Methods Recombinant E2-CSFV protein produced by baculovirus/insect cell system was analyzed by western blots and immunoperoxidase monolayer assay. The effect of CSFV-E2 subunit vaccines was evaluated in experimental pigs with three genotypes of CSFV challenge. Anti-E2 specific and neutralizing antibodies in experimental pigs were analyzed by blocking enzyme-linked immunosorbent assay and neutralization peroxidize-linked assay. Results The data showed that CSFV VN91-E2 subunit vaccine provided clinical protection in pigs against three different genotypes of CSFV without noticeable clinical signs, symptoms, and mortality. In addition, no CSFV was isolated from the spleen of the vaccinated pigs. However, the unvaccinated pigs exhibited high clinical scores and the successful virus isolation from spleen.
Intervention effects were assessed by mixed analysis of variance. Somatic, psychological, and urogenital symptoms were immediately alleviated after the marine healing program. No effect of sea mustard was detected in the marine group. After 2 weeks, the effect of marine healing persisted in physical and mental exhaustion only. A 5-day integrated marine healing program, but not additional sea mustard intake, temporarily alleviated menopausal symptoms. The reduction in physical and mental exhaustion after marine healing can be maintained for 2 weeks. Trial Registration Clinical Research Information Service Identifier KCT0004025. Mumps is contagious disease and maintaining immunity to mumps in healthcare worker (HCW) is important for preventing transmission in the hospital. We evaluated the seroprevalence of mumps in HCWs in a tertiary care hospital in Republic of Korea. A total of 6,055 HCWs born between 1950 and 1995 underwent antibody testing. The overall seropositivity rate of mumps was 87% (95% confidence interval, 86%-87%). Our data indicates that, in Korean HCWs, testing for mumps antibody followed by mumps vaccination is more appropriate than routine mumps vaccination without testing for mumps antibody. © Korean Vaccine Society.Purpose When influenza viruses are cultured in eggs, amino acid mutations of the hemagglutinin may occur through egg adaptation. On the other hand, when influenza viruses are cultured in animal cells, no antigenic mutation occurs unlike in eggs. Therefore, we examined whether the antigenic mutations actually occurred after passage of H3N2 (A/Texas/50/2012) virus up to 15 times in eggs and MDCK-Sky3851 cells. Materials and Methods Prototype A/Texas/50/2012 (H3N2) influenza virus which was isolated from clinical patient, not passaged in egg, was obtained and propagated using the specific pathogen free egg and the MDCK-Sky3851 cell line up to 15 passage, and the changes in the antigen sequence of the influenza viruses were confirmed by gene sequencing and protein structure analysis. Results In term of the hemagglutination titer of influenza virus, the reactivity to chicken and guinea pig red blood cell showed different results between egg propagated and cell propagated viruses. In the sequence analysis results for hemagglutinin and neuraminidase, no antigenic mutation was observed throughout all passages when cultured in MDCK-Sky3851 cells. On the other hand, mutations occurred in three amino acid sequences (H156R, G186S, S219F) in hemagglutinin up to 15 passages when cultured in eggs. Conclusion H3N2 influenza virus cultured in eggs could lead mutations in amino acid sequence of hemagglutinin, distinct from the corresponding virus cultured in cells for which no antigenic mutation was observed. These findings suggest that cell culture is a more stable and effective way of production with lower risk of antigenic mutations for the manufacture of influenza vaccines. © Korean Vaccine Society.Purpose Most cell culture processes for viral vaccine production are mainly based on adherent cell culture systems using serum, which are associated with expensive and labor-intensive processes to produce large amounts of viral vaccine strains. In this study, we investigated whether Vero cells could be grown in serum-free and shaking suspension conditions. Furthermore, we assessed the ability of the Vero cell suspension culture system to produce adenovirus type 5 (Ad5), compared to that of the adhesive Vero cell culture system. Materials and Methods We tested the feasibility of commercial serum-free media for Vero cell culture. For the adaptation of Vero cells in suspension culture, adhesive Vero cells were added in the early phase of shaking suspension culture, and 50 days after shaking suspension culture, suspension-adapted Vero cells were subcultured continuously. To assess the virus production ability of Vero cells in suspension, the cells were infected with Ad5-green fluorescent protein and evaluated based on their fluorescence intensity. Results The Vero cells grown in OptiPRO serum-free medium showed no changes in morphology and growth rate, but MRC-5 and FRhk-4 cells showed morphological changes and decreased growth rate, respectively. The Vero cells were well adapted to the suspension culture system. The Vero cells in suspension showed a better Ad5 production ability than the adherent Vero cells. Conclusion Vero cells can be grown in OptiPRO serum-free medium. Further, our suspension culture-adapted Vero cells may be suitable to produce viral vaccine strains due to their high ability to produce viruses such as Ad5. © Korean Vaccine Society.Purpose We constructed a new canine adenovirus type 2 (CAV-2) vaccine candidate using the recently isolated Korean CAV-2 strain; we termed the vaccine APQA1701-40P and evaluated its safety and immunogenicity in dogs. Materials and Methods To generate the anti-CAV-2 vaccine, APQA1701 was passaged 40 times in MDCK cells growing in medium containing 5 mM urea and the virus was inactivated using 0.05% (volume per volume) formaldehyde. Two vaccines were prepared by blending inactivated APQA1701-40P with two different adjuvants; both were intramuscularly injected (twice) into guinea pigs. The safety and immunogenicity of the Cabopol-adjuvanted vaccine were evaluated in seronegative dogs. The humoral responses elicited were measured using an indirect enzyme-linked immunosorbent assay (I-ELISA), and via a virus neutralization assay (VNA). https://www.selleckchem.com/products/gossypol.html Results The new, inactivated CAV-2 vaccine strain, APQA1701-40P, lacked six amino acids of the E1b-19K protein. In guinea pigs, the Cabopol-adjuvanted vaccine afforded a slightly higher VNA titer and I-ELISA absorbance than an IMS gel-adjuvanted vaccine 4 weeks post-vaccination (p>0.05). Dogs inoculated with the former vaccine developed a significantly higher immune titer than non-vaccinated dogs. Conclusion The Cabopol-adjuvanted, inactivated CAV-2 vaccine was safe and induced a high VNA titer in dogs. © Korean Vaccine Society.Purpose To date, many kinds of classical swine fever (CSF) vaccines have been developed to protect against this disease. However, the efficacy of these vaccines to protect the pig against field CSF strains needs to be considered, based on circulating strains of classical swine fever virus (CSFV). Materials and Methods Recombinant E2-CSFV protein produced by baculovirus/insect cell system was analyzed by western blots and immunoperoxidase monolayer assay. The effect of CSFV-E2 subunit vaccines was evaluated in experimental pigs with three genotypes of CSFV challenge. Anti-E2 specific and neutralizing antibodies in experimental pigs were analyzed by blocking enzyme-linked immunosorbent assay and neutralization peroxidize-linked assay. Results The data showed that CSFV VN91-E2 subunit vaccine provided clinical protection in pigs against three different genotypes of CSFV without noticeable clinical signs, symptoms, and mortality. In addition, no CSFV was isolated from the spleen of the vaccinated pigs. However, the unvaccinated pigs exhibited high clinical scores and the successful virus isolation from spleen.0 Comments 0 Shares 67 Views 0 Reviews
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