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  • In the pharmaceutical industry, cryoprotectants are added to buffer formulations to protect the active pharmaceutical ingredient from freeze- and thaw damage. We investigated the freezing and thawing of aqueous sodium citrate buffer with various cryoprotectants, specifically amino acids (cysteine, histidine, arginine, proline and lysine), disaccharides (trehalose and sucrose), polyhydric alcohols (glycerol and mannitol) and surfactants (polysorbate 20 and polysorbate 80). Hereby, we employed optical cryomicroscopy in combination with differential scanning calorimetry in the temperature range to -80 °C. The effect of cryoprotectants on the morphology of the ice crystals, the glass transition temperature and the initial melting temperature is presented. Some of the cryoprotectants have a significant impact on ice crystal size. Disaccharides restrict ice crystal growth, whereas surfactants and glycerol allow ice crystals to increase in size. Cysteine and mannitol cause dehydration after thawing. Either one or two glass transition temperatures were detected, where arginine, surfactants, glycerol, proline and lysine suppress the second, implying a uniform freeze-concentrated solution. The initial melting temperature of pure buffer solution can be shifted up by adding mannitol, both disaccharides and both surfactants; but down by glycerol, proline and lysine.Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9-18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. https://www.selleckchem.com/products/grl0617.html Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.Although it is well established that chlamydial disease renders female koalas infertile, there has been limited research on its effects on male koala fertility, specifically sperm quality. This study determined whether chlamydial infection adversely affects semen quality of naturally infected koalas and spermatozoa recovered from Chlamydia negative koalas co-incubated in vitro with C. pecorum elementary bodies (EBs). Semen from 102 south-east Queensland sexually mature wild koalas exhibiting varying degrees of chlamydiosis and clinical signs of disease were assessed for semen quality and compared to 11 clinically healthy, Chlamydia-free captive male koalas. For in vitro studies, semen samples were collected from 6 Chlamydia-free captive koalas, and co-incubated over 24 h with high and low concentrations of C. pecorum EBs and sperm quality assessed. Wild koalas displaying severe signs of clinical disease with C. pecorum present in the semen had significantly greater sperm DNA damage (P = 0.0267). The total % of morphologically abnormal spermatozoa was highest in wild koalas that had severe signs of clinical disease but whose semen was negative for C. pecorum (P = 0.0328). This apparent contradiction is possibly associated with wild males having resolved the infection but still possessing underlining reproductive pathology. A higher incidence of loose head spermatozoa occurred in semen of wild koalas not infected with C. pecorum compared to those that were C. pecorum infected (P = 0.026). In vitro incubation of semen with C. pecorum significantly decreased sperm motility and viability over 24 h.Identification of factors associated with the quality and quantity of colostrum production has always been a major challenge in cattle industry. In purebred double-muscled Belgian Blue (BB) cows, parturition is mainly performed by elective caesarean section (CS; >90%). However, the CS itself may influence colostrum production characteristics. The present study aimed to evaluate the impact of maternal and newborn calf factors and the duration of the procedure of CS on the quality and quantity of colostrum production in BB cows. The dataset includes 551 records of ***-calf pairs that were presented for an elective CS at the Ghent University veterinary clinic between 2017 and 2019. The quality (measured via a colostrum densimeter) and the quantity (measured via a standard volume scale) of colostrum were measured within 30 min after the end of the CS. Fixed effects were fitted in mixed linear regression models to test for their potential association with colostrum quality (specific gravity; SG) and quantity (liters), and generalized mixed-effects models were constructed to test the associations of fixed effects with the optimal colostrum production index (yes vs no) based on an adequate supply of both colostrum quality and quantity. The fixed effects tested were parity, the gender of the calf, birth weight, duration of CS (min), and season of birth. Our results show that parity (primiparity), duration of CS (longer CS), and calving season (summer) had a significantly negative impact on colostrum production. Concluding, both colostrum quality and quantity can be influenced by intrinsic and extrinsic factors (including duration of CS), which should be considered while feeding newborn calves delivered via CS.
    In the pharmaceutical industry, cryoprotectants are added to buffer formulations to protect the active pharmaceutical ingredient from freeze- and thaw damage. We investigated the freezing and thawing of aqueous sodium citrate buffer with various cryoprotectants, specifically amino acids (cysteine, histidine, arginine, proline and lysine), disaccharides (trehalose and sucrose), polyhydric alcohols (glycerol and mannitol) and surfactants (polysorbate 20 and polysorbate 80). Hereby, we employed optical cryomicroscopy in combination with differential scanning calorimetry in the temperature range to -80 °C. The effect of cryoprotectants on the morphology of the ice crystals, the glass transition temperature and the initial melting temperature is presented. Some of the cryoprotectants have a significant impact on ice crystal size. Disaccharides restrict ice crystal growth, whereas surfactants and glycerol allow ice crystals to increase in size. Cysteine and mannitol cause dehydration after thawing. Either one or two glass transition temperatures were detected, where arginine, surfactants, glycerol, proline and lysine suppress the second, implying a uniform freeze-concentrated solution. The initial melting temperature of pure buffer solution can be shifted up by adding mannitol, both disaccharides and both surfactants; but down by glycerol, proline and lysine.Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9-18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. https://www.selleckchem.com/products/grl0617.html Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed.Although it is well established that chlamydial disease renders female koalas infertile, there has been limited research on its effects on male koala fertility, specifically sperm quality. This study determined whether chlamydial infection adversely affects semen quality of naturally infected koalas and spermatozoa recovered from Chlamydia negative koalas co-incubated in vitro with C. pecorum elementary bodies (EBs). Semen from 102 south-east Queensland sexually mature wild koalas exhibiting varying degrees of chlamydiosis and clinical signs of disease were assessed for semen quality and compared to 11 clinically healthy, Chlamydia-free captive male koalas. For in vitro studies, semen samples were collected from 6 Chlamydia-free captive koalas, and co-incubated over 24 h with high and low concentrations of C. pecorum EBs and sperm quality assessed. Wild koalas displaying severe signs of clinical disease with C. pecorum present in the semen had significantly greater sperm DNA damage (P = 0.0267). The total % of morphologically abnormal spermatozoa was highest in wild koalas that had severe signs of clinical disease but whose semen was negative for C. pecorum (P = 0.0328). This apparent contradiction is possibly associated with wild males having resolved the infection but still possessing underlining reproductive pathology. A higher incidence of loose head spermatozoa occurred in semen of wild koalas not infected with C. pecorum compared to those that were C. pecorum infected (P = 0.026). In vitro incubation of semen with C. pecorum significantly decreased sperm motility and viability over 24 h.Identification of factors associated with the quality and quantity of colostrum production has always been a major challenge in cattle industry. In purebred double-muscled Belgian Blue (BB) cows, parturition is mainly performed by elective caesarean section (CS; >90%). However, the CS itself may influence colostrum production characteristics. The present study aimed to evaluate the impact of maternal and newborn calf factors and the duration of the procedure of CS on the quality and quantity of colostrum production in BB cows. The dataset includes 551 records of cow-calf pairs that were presented for an elective CS at the Ghent University veterinary clinic between 2017 and 2019. The quality (measured via a colostrum densimeter) and the quantity (measured via a standard volume scale) of colostrum were measured within 30 min after the end of the CS. Fixed effects were fitted in mixed linear regression models to test for their potential association with colostrum quality (specific gravity; SG) and quantity (liters), and generalized mixed-effects models were constructed to test the associations of fixed effects with the optimal colostrum production index (yes vs no) based on an adequate supply of both colostrum quality and quantity. The fixed effects tested were parity, the gender of the calf, birth weight, duration of CS (min), and season of birth. Our results show that parity (primiparity), duration of CS (longer CS), and calving season (summer) had a significantly negative impact on colostrum production. Concluding, both colostrum quality and quantity can be influenced by intrinsic and extrinsic factors (including duration of CS), which should be considered while feeding newborn calves delivered via CS.
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  • The purpose of the study was to evaluate the agreement between the Fels and Greulich-Pyle methods for the assessment of skeletal age (SA) in female youth soccer players.

    The sample included 441 Portuguese players 10.08-16.73 years of age who regularly participated in organized and competitive soccer. Standardized radiographs of the left hand-wrist were obtained and analyzed by an experienced examiner. SA was estimated with the Fels and Greulich-Pyle (GP) methods. Differences between SA and chronological age (CA) were used to define skeletal maturity groups late, average and early maturing. In addition to descriptive statistics, Cohen's kappa and Lin concordance correlation coefficients were used to evaluate agreement between methods.

    Intraindividual differences in SA based on the two methods varied between 0.10 to 1.47 years among age groups with larger mean differences at older ages. Agreement of maturity classifications between methods was 74% at younger ages (under-13 kappa = 0.48; under-14 kappa = 0.39; Lin CCC = 0.68) and declined with increasing CA (under-17 19% agreement; kappa = 0.001; Lin CCC = 0.11). About 19% of the total sample was skeletally mature with the Fels method and an SA was not assigned; in contrast, no players were skeletally mature with the GP method.

    GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. The findings highlight the impact of method on estimates of maturity status.
    GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. https://www.selleckchem.com/products/ccs-1477-cbp-in-1-.html The findings highlight the impact of method on estimates of maturity status.
    This study aimed to identify the resources recognized as helpful by children of parents with a mental illness (COPMI) to cope with the difficulties they experienced in their lives.

    A qualitative descriptive design was employed. Semi-structured interviews were conducted with 10 adults who experienced parental mental illness in their childhood. Participants were asked to discuss resources that were beneficial to them. Text segments from the verbatim transcriptions were identified with summarizing codes, and the codes were compared and contrasted to generate subcategories and categories. The case characteristics and subcategories were reorganized to retest the validity of the categories.

    Parental mental illness onset occurred before birth or in early childhood for four participants and during elementary or junior high school for six participants. Six categories emerged protection from the harmful influences of parents' symptoms; care received from adults at home and school; occasional experience of mutual tal illness.In the traditional biogeographic model, the Galápagos Islands appeared a few million years ago in a sea where no other islands existed and were colonized from areas outside the region. However, recent work has shown that the Galápagos hotspot is 139 million years old (Early Cretaceous), and so groups are likely to have survived at the hotspot by dispersal of populations onto new islands from older ones. This process of metapopulation dynamics means that species can persist indefinitely in an oceanic region, as long as new islands are being produced. Metapopulations can also undergo vicariance into two metapopulations, for example at active island arcs that are rifted by transform faults. We reviewed the geographic relationships of Galápagos groups and found 10 biogeographic patterns that are shared by at least two groups. Each of the patterns coincides spatially with a major tectonic structure; these structures include the East Pacific Rise; west Pacific and American subduction zones; large igneous plateaus in the Pacific; Alisitos terrane (Baja California), Guerrero terrane (western Mexico); rifting of North and South America; formation of the Caribbean Plateau by the Galápagos hotspot, and its eastward movement; accretion of Galápagos hotspot tracks; Andean uplift; and displacement on the Romeral fault system. All these geological features were active in the Cretaceous, suggesting that geological change at that time caused vicariance in widespread ancestors. The present distributions are explicable if ancestors survived as metapopulations occupying both the Galápagos hotspot and other regions before differentiating, more or less in situ.The generation of bioactive molecules from inactive precursors is a crucial step in the chemical evolution of life, however, mechanistic insights into this aspect of abiogenesis are scarce. Here, we investigate the protein-catalyzed formation of antivirals by the 3C-protease of enterovirus D68. The enzyme induces aldol condensations yielding inhibitors with antiviral activity in cells. Kinetic and thermodynamic analyses reveal that the bioactivity emerges from a dynamic reaction system including inhibitor formation, alkylation of the protein target by the inhibitors, and competitive addition of non-protein nucleophiles to the inhibitors. The most active antivirals are slowly reversible inhibitors with elongated target residence times. The study reveals first examples for the chemical evolution of bio-actives through protein-catalyzed, non-enzymatic C-C couplings. The discovered mechanism works under physiological conditions and might constitute a native process of drug development.
    Electromagnetic navigation bronchoscopy (ENB) is a useful method to obtain tissue for peripheral lung nodules. We aimed to understand the diagnostic yield and safety profile in high-risk pulmonary nodules that cannot be accessed by percutaneous transthoracic needle biopsy.

    In this single-center retrospective study, we reviewed patients who underwent ENB for high-risk pulmonary nodules. All procedures were performed under moderate sedation using intravenous midazolam and fentanyl.

    A total of 100 pulmonary nodules in 90 patients were subjected to ENB between October 2018 and May 2020. The median age of the study population was 66 (59-73). The mean diameter of the lung nodules was 27.9 mm. The diagnostic yield of ENB-guided biopsy was 53.0%. Although the nodule size (odds ratio 1.055, p = 0.007) and positive bronchus sign (odds ratio 2.918, p = 0.020) were associated with the diagnostic yield during univariate analysis, nodule size was the only independent variable on the multivariable analysis. Interestingly, the diagnostic yield showed an upward trend after 60 cases, from 45%-65%.
    The purpose of the study was to evaluate the agreement between the Fels and Greulich-Pyle methods for the assessment of skeletal age (SA) in female youth soccer players. The sample included 441 Portuguese players 10.08-16.73 years of age who regularly participated in organized and competitive soccer. Standardized radiographs of the left hand-wrist were obtained and analyzed by an experienced examiner. SA was estimated with the Fels and Greulich-Pyle (GP) methods. Differences between SA and chronological age (CA) were used to define skeletal maturity groups late, average and early maturing. In addition to descriptive statistics, Cohen's kappa and Lin concordance correlation coefficients were used to evaluate agreement between methods. Intraindividual differences in SA based on the two methods varied between 0.10 to 1.47 years among age groups with larger mean differences at older ages. Agreement of maturity classifications between methods was 74% at younger ages (under-13 kappa = 0.48; under-14 kappa = 0.39; Lin CCC = 0.68) and declined with increasing CA (under-17 19% agreement; kappa = 0.001; Lin CCC = 0.11). About 19% of the total sample was skeletally mature with the Fels method and an SA was not assigned; in contrast, no players were skeletally mature with the GP method. GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. The findings highlight the impact of method on estimates of maturity status. GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. https://www.selleckchem.com/products/ccs-1477-cbp-in-1-.html The findings highlight the impact of method on estimates of maturity status. This study aimed to identify the resources recognized as helpful by children of parents with a mental illness (COPMI) to cope with the difficulties they experienced in their lives. A qualitative descriptive design was employed. Semi-structured interviews were conducted with 10 adults who experienced parental mental illness in their childhood. Participants were asked to discuss resources that were beneficial to them. Text segments from the verbatim transcriptions were identified with summarizing codes, and the codes were compared and contrasted to generate subcategories and categories. The case characteristics and subcategories were reorganized to retest the validity of the categories. Parental mental illness onset occurred before birth or in early childhood for four participants and during elementary or junior high school for six participants. Six categories emerged protection from the harmful influences of parents' symptoms; care received from adults at home and school; occasional experience of mutual tal illness.In the traditional biogeographic model, the Galápagos Islands appeared a few million years ago in a sea where no other islands existed and were colonized from areas outside the region. However, recent work has shown that the Galápagos hotspot is 139 million years old (Early Cretaceous), and so groups are likely to have survived at the hotspot by dispersal of populations onto new islands from older ones. This process of metapopulation dynamics means that species can persist indefinitely in an oceanic region, as long as new islands are being produced. Metapopulations can also undergo vicariance into two metapopulations, for example at active island arcs that are rifted by transform faults. We reviewed the geographic relationships of Galápagos groups and found 10 biogeographic patterns that are shared by at least two groups. Each of the patterns coincides spatially with a major tectonic structure; these structures include the East Pacific Rise; west Pacific and American subduction zones; large igneous plateaus in the Pacific; Alisitos terrane (Baja California), Guerrero terrane (western Mexico); rifting of North and South America; formation of the Caribbean Plateau by the Galápagos hotspot, and its eastward movement; accretion of Galápagos hotspot tracks; Andean uplift; and displacement on the Romeral fault system. All these geological features were active in the Cretaceous, suggesting that geological change at that time caused vicariance in widespread ancestors. The present distributions are explicable if ancestors survived as metapopulations occupying both the Galápagos hotspot and other regions before differentiating, more or less in situ.The generation of bioactive molecules from inactive precursors is a crucial step in the chemical evolution of life, however, mechanistic insights into this aspect of abiogenesis are scarce. Here, we investigate the protein-catalyzed formation of antivirals by the 3C-protease of enterovirus D68. The enzyme induces aldol condensations yielding inhibitors with antiviral activity in cells. Kinetic and thermodynamic analyses reveal that the bioactivity emerges from a dynamic reaction system including inhibitor formation, alkylation of the protein target by the inhibitors, and competitive addition of non-protein nucleophiles to the inhibitors. The most active antivirals are slowly reversible inhibitors with elongated target residence times. The study reveals first examples for the chemical evolution of bio-actives through protein-catalyzed, non-enzymatic C-C couplings. The discovered mechanism works under physiological conditions and might constitute a native process of drug development. Electromagnetic navigation bronchoscopy (ENB) is a useful method to obtain tissue for peripheral lung nodules. We aimed to understand the diagnostic yield and safety profile in high-risk pulmonary nodules that cannot be accessed by percutaneous transthoracic needle biopsy. In this single-center retrospective study, we reviewed patients who underwent ENB for high-risk pulmonary nodules. All procedures were performed under moderate sedation using intravenous midazolam and fentanyl. A total of 100 pulmonary nodules in 90 patients were subjected to ENB between October 2018 and May 2020. The median age of the study population was 66 (59-73). The mean diameter of the lung nodules was 27.9 mm. The diagnostic yield of ENB-guided biopsy was 53.0%. Although the nodule size (odds ratio 1.055, p = 0.007) and positive bronchus sign (odds ratio 2.918, p = 0.020) were associated with the diagnostic yield during univariate analysis, nodule size was the only independent variable on the multivariable analysis. Interestingly, the diagnostic yield showed an upward trend after 60 cases, from 45%-65%.
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  • Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene (GAD1) was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. GAD1 catalyzes the production of γ-aminobutyric acid from L-glutamic acid. GAD1 expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of GAD1 were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of GAD1 were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and GAD1 methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of GAD1 were significantly higher in TC tissues than in thymomas. Patients with TET with high GAD1 DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.Tumor development and progression are closely associated with various microRNAs (miRNAs/miRs). We have previously shown that Newcastle disease virus (NDV) strain 7793 induces oncolysis in lung cancer. However, how NDV exerts its oncolytic effect on lung cancer remains to be investigated. The present study assessed the role of miR-204 in the NDV-induced oncolysis of lung cancer A549 cells by oncolysis induction in vitro. miR-204 was significantly upregulated in NDV-treated A549 cells. Overexpression or inhibition of miR-204 was significantly associated with NDV-induced oncolysis in A549 cells. Caspase-3 and Bax, major regulators of the apoptosis pathway, were regulated by miR-204, and the association between caspase-3-related apoptosis and miR-204 was identified in NDV-mediated oncolysis. These data demonstrated that miR-204 as a tumor suppressor played a role in NDV-induced oncolysis in lung cancer cells. The present study demonstrates the potential of strategies using miRs to improve oncolytic NDV potency, and highlights miR-204 as a tumor suppressor in NDV-induced oncolysis of lung cancer cells.The efficacy of chemotherapy for colon cancer is limited due to the development of chemoresistance. MicroRNA (miR)-188-5p is downregulated in various types of cancer. https://www.selleckchem.com/products/AZD0530.html The aim of the present study was to explore the molecular role of miR-188 in oxaliplatin (OXA) resistance. An OXA-resistant colon cancer cell line, SW480/OXA, was used to examine the effects of miR-188-5p on the sensitivity of colon cancer cells to OXA. The target of miR-188-5p was identified using a luciferase assay. Cell cycle distribution was also assessed using flow cytometry. The measurement of p21 protein expression, Hoechst 33342 staining and Annexin V/propidium iodide staining was used to evaluate apoptosis. The expression of miR-188-5p significantly increased in SW480/OXA compared with wild-type SW480 cells. The luciferase assay demonstrated that miR-188-5p inhibited Ras GTPase-activating protein 1 (RASA1; also known as p120/RasGAP) luciferase activity by binding to the 3'-untranslated region of RASA1 mRNA, suggesting that miR-188-5p could target RASA1. In addition, miR-188-5p downregulation or RASA1 overexpression promoted the chemosensitivity of SW480/OXA, as evidenced by increased apoptosis and G1/S cell cycle arrest. Moreover, RASA1 silencing abrogated the increase in cell apoptosis induced by the miR-188-5p inhibitor. The findings of the present study suggested that miR-188-5p could enhance colon cancer cell chemosensitivity by promoting the expression of RASA1.[This corrects the article DOI 10.3892/ol.2021.12474.].Wild-type (wt) p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D) gene, is a serine/threonine phosphatase induced upon genotoxic stress in a p53-dependent manner. Wip1/PPM1D is frequently overexpressed, amplified and mutated in human solid tumors harboring wt p53 and is thus currently recognized as an oncogene. Oncogenic Wip1 dampens cellular stress responses, such as cell cycle checkpoints, apoptosis and senescence, and consequently increases resistance to anticancer therapeutics. Targeting Wip1 has emerged as a therapeutic strategy for tumors harboring wt p53. However, little is known about the efficacy of Wip1-targeted therapies in tumors lacking p53. The present study aimed to investigate the potential role of oncogenic Wip1 in p53 mutant (mt) Jurkat cells. In the present study, it was demonstrated that p53 mt Jurkat cells exhibited PPM1D/Wip1 gene amplification and expressed relatively high levels of Wip1, as confirmed by gene copy number and RNA expressistrategies aiming to manipulate or target Wip1 in human cancers lacking p53.Complement factor B (CFB) serves a pivotal role in the alternative signaling pathway of the complement system and exerts a key role in the labelling of target particles, resulting from effective clearance of the target. The present study aimed to investigate the association between low expression levels of CFB and the clinical features and survival status of patients with lung adenocarcinoma (LUAD). Patient data were based on RNA-sequencing and clinical data from The Cancer Genome Atlas database. All patients were divided into two groups based on the median expression of CFB. Kaplan-Meier curve and univariate Cox regression analyses were used to investigate the association between CFB and survival status. Gene set enrichment analysis was used to examine the effects of CFB expression on signaling pathway impairment. Furthermore, reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to verify the relative expression levels of CFB in LUAD tissues. The data revealed that residual tumor classification, Karnofsky performance score and cancer stage were associated with overall survival, and that Karnofsky performance score and stage were associated with disease-free survival.
    Thymic epithelial tumors (TETs) comprise thymomas and thymic carcinoma (TC). TC has more aggressive features and a poorer prognosis than thymomas. Genetic and epigenetic alterations in thymomas and TC have been investigated in an attempt to identify novel target molecules for TC. In the present study, genome-wide screening was performed on aberrantly methylated CpG islands in thymomas and TC, and the glutamate decarboxylase 1 gene (GAD1) was identified as the 4th significantly hypermethylated CpG island in TC compared with thymomas. GAD1 catalyzes the production of γ-aminobutyric acid from L-glutamic acid. GAD1 expression is abundant in the brain but rare in other tissues, including the thymus. A total of 73 thymomas and 17 TC tissues were obtained from 90 patients who underwent surgery or biopsy at Tokushima University Hospital between 1990 and 2017. DNA methylation was examined by bisulfite pyrosequencing, and the mRNA and protein expression levels of GAD1 were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The DNA methylation levels of GAD1 were significantly higher in TC tissues than in the normal thymus and thymoma tissues, and GAD1 methylation exhibited high sensitivity and specificity for discriminating between TC and thymoma. The mRNA and protein expression levels of GAD1 were significantly higher in TC tissues than in thymomas. Patients with TET with high GAD1 DNA hypermethylation and high mRNA and protein expression levels had significantly shorter relapse-free survival rates than those with low levels. In conclusion, significantly more epigenetic alterations were observed in TC tissues compared with in thymomas, which may contribute to the clinical features and prognosis of patients.Tumor development and progression are closely associated with various microRNAs (miRNAs/miRs). We have previously shown that Newcastle disease virus (NDV) strain 7793 induces oncolysis in lung cancer. However, how NDV exerts its oncolytic effect on lung cancer remains to be investigated. The present study assessed the role of miR-204 in the NDV-induced oncolysis of lung cancer A549 cells by oncolysis induction in vitro. miR-204 was significantly upregulated in NDV-treated A549 cells. Overexpression or inhibition of miR-204 was significantly associated with NDV-induced oncolysis in A549 cells. Caspase-3 and Bax, major regulators of the apoptosis pathway, were regulated by miR-204, and the association between caspase-3-related apoptosis and miR-204 was identified in NDV-mediated oncolysis. These data demonstrated that miR-204 as a tumor suppressor played a role in NDV-induced oncolysis in lung cancer cells. The present study demonstrates the potential of strategies using miRs to improve oncolytic NDV potency, and highlights miR-204 as a tumor suppressor in NDV-induced oncolysis of lung cancer cells.The efficacy of chemotherapy for colon cancer is limited due to the development of chemoresistance. MicroRNA (miR)-188-5p is downregulated in various types of cancer. https://www.selleckchem.com/products/AZD0530.html The aim of the present study was to explore the molecular role of miR-188 in oxaliplatin (OXA) resistance. An OXA-resistant colon cancer cell line, SW480/OXA, was used to examine the effects of miR-188-5p on the sensitivity of colon cancer cells to OXA. The target of miR-188-5p was identified using a luciferase assay. Cell cycle distribution was also assessed using flow cytometry. The measurement of p21 protein expression, Hoechst 33342 staining and Annexin V/propidium iodide staining was used to evaluate apoptosis. The expression of miR-188-5p significantly increased in SW480/OXA compared with wild-type SW480 cells. The luciferase assay demonstrated that miR-188-5p inhibited Ras GTPase-activating protein 1 (RASA1; also known as p120/RasGAP) luciferase activity by binding to the 3'-untranslated region of RASA1 mRNA, suggesting that miR-188-5p could target RASA1. In addition, miR-188-5p downregulation or RASA1 overexpression promoted the chemosensitivity of SW480/OXA, as evidenced by increased apoptosis and G1/S cell cycle arrest. Moreover, RASA1 silencing abrogated the increase in cell apoptosis induced by the miR-188-5p inhibitor. The findings of the present study suggested that miR-188-5p could enhance colon cancer cell chemosensitivity by promoting the expression of RASA1.[This corrects the article DOI 10.3892/ol.2021.12474.].Wild-type (wt) p53-induced phosphatase 1 (Wip1), encoded by the protein phosphatase, Mg2+/Mn2+ dependent 1D (PPM1D) gene, is a serine/threonine phosphatase induced upon genotoxic stress in a p53-dependent manner. Wip1/PPM1D is frequently overexpressed, amplified and mutated in human solid tumors harboring wt p53 and is thus currently recognized as an oncogene. Oncogenic Wip1 dampens cellular stress responses, such as cell cycle checkpoints, apoptosis and senescence, and consequently increases resistance to anticancer therapeutics. Targeting Wip1 has emerged as a therapeutic strategy for tumors harboring wt p53. However, little is known about the efficacy of Wip1-targeted therapies in tumors lacking p53. The present study aimed to investigate the potential role of oncogenic Wip1 in p53 mutant (mt) Jurkat cells. In the present study, it was demonstrated that p53 mt Jurkat cells exhibited PPM1D/Wip1 gene amplification and expressed relatively high levels of Wip1, as confirmed by gene copy number and RNA expressistrategies aiming to manipulate or target Wip1 in human cancers lacking p53.Complement factor B (CFB) serves a pivotal role in the alternative signaling pathway of the complement system and exerts a key role in the labelling of target particles, resulting from effective clearance of the target. The present study aimed to investigate the association between low expression levels of CFB and the clinical features and survival status of patients with lung adenocarcinoma (LUAD). Patient data were based on RNA-sequencing and clinical data from The Cancer Genome Atlas database. All patients were divided into two groups based on the median expression of CFB. Kaplan-Meier curve and univariate Cox regression analyses were used to investigate the association between CFB and survival status. Gene set enrichment analysis was used to examine the effects of CFB expression on signaling pathway impairment. Furthermore, reverse transcription-quantitative PCR (RT-qPCR) and western blotting were used to verify the relative expression levels of CFB in LUAD tissues. The data revealed that residual tumor classification, Karnofsky performance score and cancer stage were associated with overall survival, and that Karnofsky performance score and stage were associated with disease-free survival.
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  • In August 2020, patient presented pain in her left foot. 99mTc-DPD bone scintigraphy showed multiple uptakes regarding osteolytic lesion of the left lower limb with no other pathological uptake. Echo-guided tibial biopsies confirmed breast origin adenocarcinoma, in favor of relapse of the originally treated cancer.
    To determine whether the development of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) specifically relates to dopaminergic depletion in sensorimotor-related subregions of the striatum.

    Our primary study sample consisted of 185 locally recruited PD patients, of which 73 (40%) developed LID. Retrospective 123I-FP-CIT SPECT data were used to quantify the specific dopamine transporter (DAT) binding ratio within distinct functionally defined striatal subregions related to limbic, executive, and sensorimotor systems. Regional DAT levels were contrasted between patients who developed LID (PD + LID) and those who did not (PD-LID) using analysis of covariance models controlled for demographic and clinical features. For validation of the findings and assessment of the evolution of LID-associated DAT changes from an early disease stage, we also studied serial 123I-FP-CIT SPECT data from 343 de novo PD patients enrolled in the Parkinson Progression Marker's Initiative using mixed linear model analysis.
    and could improve individual prognosis of this common clinical complication in PD.
    A 30-year-old woman with esophageal squamous cell carcinoma experienced joint pain and swelling in bilateral knees, wrists, and hand joints during the course of neoadjuvant immunochemotherapy. She underwent 18F-FDG and 68Ga-FAPI PET/CT for response assessment of the tumor and evaluating her arthritis. 68Ga-FAPI PET/CT detected intense uptake in multiple joints, consistent with her polyarthritis. However, these joints showed only mild FDG uptake. The tumor was in complete response, and her polyarthritis was considered as inflammatory arthritis induced by anti-PD1.
    A 30-year-old woman with esophageal squamous cell carcinoma experienced joint pain and swelling in bilateral knees, wrists, and hand joints during the course of neoadjuvant immunochemotherapy. She underwent 18F-FDG and 68Ga-FAPI PET/CT for response assessment of the tumor and evaluating her arthritis. 68Ga-FAPI PET/CT detected intense uptake in multiple joints, consistent with her polyarthritis. However, these joints showed only mild FDG uptake. The tumor was in complete response, and her polyarthritis was considered as inflammatory arthritis induced by anti-PD1.
    PET using 68Ga-labeled somatostatin receptor (SSTR) ligands adds significant information in meningioma patients. 18F-SiTATE is a novel, 18F-labeled SSTR-targeting peptide with remarkable imaging properties. Here, we present a 72-year-old woman with falx meningioma and transosseous extension. 18F-SiTATE PET/CT was performed 12 months after the previous 68Ga-DOTATOC PET/CT with comparable quantitative uptake and very good spatial resolution. So far, the widespread use of SSTR ligands for NET and meningioma imaging is hampered by cost-intensive 68Ge/68Ga generators, low activity amounts, lower spatial resolution, and short half-life. 18F-SiTATE might foster widespread use of SSTR ligands, overcoming the shortcomings of 68Ga-labeled ligands.
    PET using 68Ga-labeled somatostatin receptor (SSTR) ligands adds significant information in meningioma patients. 18F-SiTATE is a novel, 18F-labeled SSTR-targeting peptide with remarkable imaging properties. Here, we present a 72-year-old woman with falx meningioma and transosseous extension. 18F-SiTATE PET/CT was performed 12 months after the previous 68Ga-DOTATOC PET/CT with comparable quantitative uptake and very good spatial resolution. So far, the widespread use of SSTR ligands for NET and meningioma imaging is hampered by cost-intensive 68Ge/68Ga generators, low activity amounts, lower spatial resolution, and short half-life. 18F-SiTATE might foster widespread use of SSTR ligands, overcoming the shortcomings of 68Ga-labeled ligands.
    Infective endocarditis is a serious, potentially life-threatening condition. The valve leaflets and annulus are the most commonly affected sites, but involvement of the papillary muscles is extremely rare. We present the case of a 69-year-old woman who had infective endocarditis only involving the papillary muscle on 18F-FDG PET/CT.
    Infective endocarditis is a serious, potentially life-threatening condition. The valve leaflets and annulus are the most commonly affected sites, but involvement of the papillary muscles is extremely rare. We present the case of a 69-year-old woman who had infective endocarditis only involving the papillary muscle on 18F-FDG PET/CT.
    Hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis is a rare dural inflammatory disorder. We describe MRI and FDG PET/CT findings in 3 cases of hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis. Enhanced brain MRI of the 3 cases showed linear enhancement of the thickened dura matter involving the skull base, tentorium, and/or convexity. On FDG PET/CT, the thickened dura matter showed diffusely increased FDG uptake with SUVmax ranging from 5.8 to 11.3. Familiarity with these MRI and FDG PET/CT findings is helpful for correct diagnosis and treatment.
    Hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis is a rare dural inflammatory disorder. https://www.selleckchem.com/products/miransertib.html We describe MRI and FDG PET/CT findings in 3 cases of hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis. Enhanced brain MRI of the 3 cases showed linear enhancement of the thickened dura matter involving the skull base, tentorium, and/or convexity. On FDG PET/CT, the thickened dura matter showed diffusely increased FDG uptake with SUVmax ranging from 5.8 to 11.3. Familiarity with these MRI and FDG PET/CT findings is helpful for correct diagnosis and treatment.
    Pericardial synovial sarcoma is a rare malignancy. We report the case of a patient who was referred to our institution for a large pericardial effusion requiring pericardiocentesis. CT imaging revealed an inhomogeneous pericardial mass beside the right atrium, and then a PET/CT scan was performed. Standard images were inconclusive whether delayed images showed an FDG-avid pericardial lesion that was surgically removed with histological diagnosis of a poorly differentiated biphasic synovial sarcoma. When considering mediastinal or pericardial mass, a delayed PET/CT may improve lesion-to-background contrast by reducing blood pool activity.
    Pericardial synovial sarcoma is a rare malignancy. We report the case of a patient who was referred to our institution for a large pericardial effusion requiring pericardiocentesis. CT imaging revealed an inhomogeneous pericardial mass beside the right atrium, and then a PET/CT scan was performed. Standard images were inconclusive whether delayed images showed an FDG-avid pericardial lesion that was surgically removed with histological diagnosis of a poorly differentiated biphasic synovial sarcoma.
    In August 2020, patient presented pain in her left foot. 99mTc-DPD bone scintigraphy showed multiple uptakes regarding osteolytic lesion of the left lower limb with no other pathological uptake. Echo-guided tibial biopsies confirmed breast origin adenocarcinoma, in favor of relapse of the originally treated cancer. To determine whether the development of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) specifically relates to dopaminergic depletion in sensorimotor-related subregions of the striatum. Our primary study sample consisted of 185 locally recruited PD patients, of which 73 (40%) developed LID. Retrospective 123I-FP-CIT SPECT data were used to quantify the specific dopamine transporter (DAT) binding ratio within distinct functionally defined striatal subregions related to limbic, executive, and sensorimotor systems. Regional DAT levels were contrasted between patients who developed LID (PD + LID) and those who did not (PD-LID) using analysis of covariance models controlled for demographic and clinical features. For validation of the findings and assessment of the evolution of LID-associated DAT changes from an early disease stage, we also studied serial 123I-FP-CIT SPECT data from 343 de novo PD patients enrolled in the Parkinson Progression Marker's Initiative using mixed linear model analysis. and could improve individual prognosis of this common clinical complication in PD. A 30-year-old woman with esophageal squamous cell carcinoma experienced joint pain and swelling in bilateral knees, wrists, and hand joints during the course of neoadjuvant immunochemotherapy. She underwent 18F-FDG and 68Ga-FAPI PET/CT for response assessment of the tumor and evaluating her arthritis. 68Ga-FAPI PET/CT detected intense uptake in multiple joints, consistent with her polyarthritis. However, these joints showed only mild FDG uptake. The tumor was in complete response, and her polyarthritis was considered as inflammatory arthritis induced by anti-PD1. A 30-year-old woman with esophageal squamous cell carcinoma experienced joint pain and swelling in bilateral knees, wrists, and hand joints during the course of neoadjuvant immunochemotherapy. She underwent 18F-FDG and 68Ga-FAPI PET/CT for response assessment of the tumor and evaluating her arthritis. 68Ga-FAPI PET/CT detected intense uptake in multiple joints, consistent with her polyarthritis. However, these joints showed only mild FDG uptake. The tumor was in complete response, and her polyarthritis was considered as inflammatory arthritis induced by anti-PD1. PET using 68Ga-labeled somatostatin receptor (SSTR) ligands adds significant information in meningioma patients. 18F-SiTATE is a novel, 18F-labeled SSTR-targeting peptide with remarkable imaging properties. Here, we present a 72-year-old woman with falx meningioma and transosseous extension. 18F-SiTATE PET/CT was performed 12 months after the previous 68Ga-DOTATOC PET/CT with comparable quantitative uptake and very good spatial resolution. So far, the widespread use of SSTR ligands for NET and meningioma imaging is hampered by cost-intensive 68Ge/68Ga generators, low activity amounts, lower spatial resolution, and short half-life. 18F-SiTATE might foster widespread use of SSTR ligands, overcoming the shortcomings of 68Ga-labeled ligands. PET using 68Ga-labeled somatostatin receptor (SSTR) ligands adds significant information in meningioma patients. 18F-SiTATE is a novel, 18F-labeled SSTR-targeting peptide with remarkable imaging properties. Here, we present a 72-year-old woman with falx meningioma and transosseous extension. 18F-SiTATE PET/CT was performed 12 months after the previous 68Ga-DOTATOC PET/CT with comparable quantitative uptake and very good spatial resolution. So far, the widespread use of SSTR ligands for NET and meningioma imaging is hampered by cost-intensive 68Ge/68Ga generators, low activity amounts, lower spatial resolution, and short half-life. 18F-SiTATE might foster widespread use of SSTR ligands, overcoming the shortcomings of 68Ga-labeled ligands. Infective endocarditis is a serious, potentially life-threatening condition. The valve leaflets and annulus are the most commonly affected sites, but involvement of the papillary muscles is extremely rare. We present the case of a 69-year-old woman who had infective endocarditis only involving the papillary muscle on 18F-FDG PET/CT. Infective endocarditis is a serious, potentially life-threatening condition. The valve leaflets and annulus are the most commonly affected sites, but involvement of the papillary muscles is extremely rare. We present the case of a 69-year-old woman who had infective endocarditis only involving the papillary muscle on 18F-FDG PET/CT. Hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis is a rare dural inflammatory disorder. We describe MRI and FDG PET/CT findings in 3 cases of hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis. Enhanced brain MRI of the 3 cases showed linear enhancement of the thickened dura matter involving the skull base, tentorium, and/or convexity. On FDG PET/CT, the thickened dura matter showed diffusely increased FDG uptake with SUVmax ranging from 5.8 to 11.3. Familiarity with these MRI and FDG PET/CT findings is helpful for correct diagnosis and treatment. Hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis is a rare dural inflammatory disorder. https://www.selleckchem.com/products/miransertib.html We describe MRI and FDG PET/CT findings in 3 cases of hypertrophic pachymeningitis associated with antineutrophil cytoplasmic antibody-associated vasculitis. Enhanced brain MRI of the 3 cases showed linear enhancement of the thickened dura matter involving the skull base, tentorium, and/or convexity. On FDG PET/CT, the thickened dura matter showed diffusely increased FDG uptake with SUVmax ranging from 5.8 to 11.3. Familiarity with these MRI and FDG PET/CT findings is helpful for correct diagnosis and treatment. Pericardial synovial sarcoma is a rare malignancy. We report the case of a patient who was referred to our institution for a large pericardial effusion requiring pericardiocentesis. CT imaging revealed an inhomogeneous pericardial mass beside the right atrium, and then a PET/CT scan was performed. Standard images were inconclusive whether delayed images showed an FDG-avid pericardial lesion that was surgically removed with histological diagnosis of a poorly differentiated biphasic synovial sarcoma. When considering mediastinal or pericardial mass, a delayed PET/CT may improve lesion-to-background contrast by reducing blood pool activity. Pericardial synovial sarcoma is a rare malignancy. We report the case of a patient who was referred to our institution for a large pericardial effusion requiring pericardiocentesis. CT imaging revealed an inhomogeneous pericardial mass beside the right atrium, and then a PET/CT scan was performed. Standard images were inconclusive whether delayed images showed an FDG-avid pericardial lesion that was surgically removed with histological diagnosis of a poorly differentiated biphasic synovial sarcoma.
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  • Conservation breeding programs such as zoos play a major role in preventing extinction, but their sustainability may be impeded by neutral and adaptive population genetic change. These changes are difficult to detect for a single species or context, and impact global conservation efforts. We analyse pedigree data from 15 vertebrate species - over 30,000 individuals - to examine offspring survival over generations of captive breeding. Even accounting for inbreeding, we find that the impacts of increasing generations in captivity are highly variable across species, with some showing substantial increases or decreases in offspring survival over generations. We find further differences between dam and sire effects in first- versus multi-generational analysis. Crucially, our multispecies analysis reveals that responses to captivity could not be predicted from species' evolutionary (phylogenetic) relationships. Even under best-practice captive management, generational fitness changes that cannot be explained by known processes (such as inbreeding depression), are occurring.Multicolor luminescent portrayal of complexed arrays is indispensable for many aspects of science and technology. Nevertheless, challenges such as inaccessible readouts from opaque objects, a limited visible-light spectrum and restricted spectral resolution call for alternative approaches for multicolor representation. Here, we present a strategy for spatial COlor Display by Exploiting Host-guest Dynamics (CODE-HD), comprising a paramagnetic cavitand library and various guests. First, a set of lanthanide-cradled α-cyclodextrins (Ln-CDs) is designed to induce pseudo-contact shifts in the 19F-NMR spectrum of Ln-CD-bound guest. Then, capitalizing on reversible host-guest binding dynamics and using magnetization-transfer 19F-MRI, pseudo-colored maps of complexed arrays are acquired and applied in molecular-steganography scenarios, showing CODE-HD's ability to generate versatile outputs for information encoding. By exploiting the widely shifted resonances induced by Ln-CDs, the guest versatility and supramolecular systems' reversibility, CODE-HD provides a switchable, polychromatic palette, as an advanced strategy for light-free, multicolor-mapping.The vast preponderance of somatic mutations in a typical cancer are either extremely rare or have never been previously recorded in available databases that track somatic mutations. These constitute a hidden genome that contrasts the relatively small number of mutations that occur frequently, the properties of which have been studied in depth. Here we demonstrate that this hidden genome contains **** more accurate information than common mutations for the purpose of identifying the site of origin of primary cancers in settings where this is unknown. We accomplish this using a projection-based statistical method that achieves a highly effective signal condensation, by leveraging DNA sequence and epigenetic contexts using a set of meta-features that embody the mutation contexts of rare variants throughout the genome.Gene expression has provided promising insights into the pathophysiology of post-traumatic stress disorder (PTSD); however, specific regulatory transcriptomic mechanisms remain unknown. The present study addressed this limitation by performing transcriptome-wide RNA-Seq of whole-blood samples from 226 World Trade Center responders. The investigation focused on differential expression (DE) at the gene, isoform, and for the first time, alternative splicing (AS) levels associated with the symptoms of PTSD total burden, re-experiencing, avoidance, numbing, and hyperarousal subdimensions. These symptoms were associated with 76, 1, 48, 15, and 49 DE genes, respectively (FDR  less then  0.05). Moreover, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with respect to DE genes and AS events. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications in the treatment of PTSD. Overall, the findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at the gene and AS levels. The results of DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.Label-free vibrational imaging by stimulated Raman scattering (SRS) provides unprecedented insight into real-time chemical distributions. Specifically, SRS in the fingerprint region (400-1800 cm-1) can resolve multiple chemicals in a complex bio-environment. However, due to the intrinsic weak Raman cross-sections and the lack of ultrafast spectral acquisition schemes with high spectral fidelity, SRS in the fingerprint region is not viable for studying living cells or large-scale tissue samples. Here, we report a fingerprint spectroscopic SRS platform that acquires a distortion-free SRS spectrum at 10 cm-1 spectral resolution within 20 µs using a polygon scanner. Meanwhile, we significantly improve the signal-to-noise ratio by employing a spatial-spectral residual learning network, reaching a level comparable to that with 100 times integration. Collectively, our system enables high-speed vibrational spectroscopic imaging of multiple biomolecules in samples ranging from a single live microbe to a tissue slice.Single-cell RNA sequencing combined with spatial information on landmark genes enables reconstruction of spatially-resolved tissue cell atlases. However, such approaches are challenging for rare cell types, since their mRNA contents are diluted in the spatial transcriptomics bulk measurements used for landmark gene detection. In the small intestine, enterocytes, the most common cell type, exhibit zonated expression programs along the crypt-villus axis, but zonation patterns of rare cell types such as goblet and tuft cells remain uncharacterized. https://www.selleckchem.com/products/ccs-1477-cbp-in-1-.html Here, we present ClumpSeq, an approach for sequencing small clumps of attached cells. By inferring the crypt-villus location of each clump from enterocyte landmark genes, we establish spatial atlases for all epithelial cell types in the small intestine. We identify elevated expression of immune-modulatory genes in villus tip goblet and tuft cells and heterogeneous migration patterns of enteroendocrine cells. ClumpSeq can be applied for reconstructing spatial atlases of rare cell types in other tissues and tumors.
    Conservation breeding programs such as zoos play a major role in preventing extinction, but their sustainability may be impeded by neutral and adaptive population genetic change. These changes are difficult to detect for a single species or context, and impact global conservation efforts. We analyse pedigree data from 15 vertebrate species - over 30,000 individuals - to examine offspring survival over generations of captive breeding. Even accounting for inbreeding, we find that the impacts of increasing generations in captivity are highly variable across species, with some showing substantial increases or decreases in offspring survival over generations. We find further differences between dam and sire effects in first- versus multi-generational analysis. Crucially, our multispecies analysis reveals that responses to captivity could not be predicted from species' evolutionary (phylogenetic) relationships. Even under best-practice captive management, generational fitness changes that cannot be explained by known processes (such as inbreeding depression), are occurring.Multicolor luminescent portrayal of complexed arrays is indispensable for many aspects of science and technology. Nevertheless, challenges such as inaccessible readouts from opaque objects, a limited visible-light spectrum and restricted spectral resolution call for alternative approaches for multicolor representation. Here, we present a strategy for spatial COlor Display by Exploiting Host-guest Dynamics (CODE-HD), comprising a paramagnetic cavitand library and various guests. First, a set of lanthanide-cradled α-cyclodextrins (Ln-CDs) is designed to induce pseudo-contact shifts in the 19F-NMR spectrum of Ln-CD-bound guest. Then, capitalizing on reversible host-guest binding dynamics and using magnetization-transfer 19F-MRI, pseudo-colored maps of complexed arrays are acquired and applied in molecular-steganography scenarios, showing CODE-HD's ability to generate versatile outputs for information encoding. By exploiting the widely shifted resonances induced by Ln-CDs, the guest versatility and supramolecular systems' reversibility, CODE-HD provides a switchable, polychromatic palette, as an advanced strategy for light-free, multicolor-mapping.The vast preponderance of somatic mutations in a typical cancer are either extremely rare or have never been previously recorded in available databases that track somatic mutations. These constitute a hidden genome that contrasts the relatively small number of mutations that occur frequently, the properties of which have been studied in depth. Here we demonstrate that this hidden genome contains much more accurate information than common mutations for the purpose of identifying the site of origin of primary cancers in settings where this is unknown. We accomplish this using a projection-based statistical method that achieves a highly effective signal condensation, by leveraging DNA sequence and epigenetic contexts using a set of meta-features that embody the mutation contexts of rare variants throughout the genome.Gene expression has provided promising insights into the pathophysiology of post-traumatic stress disorder (PTSD); however, specific regulatory transcriptomic mechanisms remain unknown. The present study addressed this limitation by performing transcriptome-wide RNA-Seq of whole-blood samples from 226 World Trade Center responders. The investigation focused on differential expression (DE) at the gene, isoform, and for the first time, alternative splicing (AS) levels associated with the symptoms of PTSD total burden, re-experiencing, avoidance, numbing, and hyperarousal subdimensions. These symptoms were associated with 76, 1, 48, 15, and 49 DE genes, respectively (FDR  less then  0.05). Moreover, they were associated with 103, 11, 0, 43, and 32 AS events. Avoidance differed the most from other dimensions with respect to DE genes and AS events. Gene set enrichment analysis (GSEA) identified pathways involved in inflammatory and metabolic processes, which may have implications in the treatment of PTSD. Overall, the findings shed a novel light on the wide range of transcriptomic alterations associated with PTSD at the gene and AS levels. The results of DE analysis associated with PTSD subdimensions highlights the importance of studying PTSD symptom heterogeneity.Label-free vibrational imaging by stimulated Raman scattering (SRS) provides unprecedented insight into real-time chemical distributions. Specifically, SRS in the fingerprint region (400-1800 cm-1) can resolve multiple chemicals in a complex bio-environment. However, due to the intrinsic weak Raman cross-sections and the lack of ultrafast spectral acquisition schemes with high spectral fidelity, SRS in the fingerprint region is not viable for studying living cells or large-scale tissue samples. Here, we report a fingerprint spectroscopic SRS platform that acquires a distortion-free SRS spectrum at 10 cm-1 spectral resolution within 20 µs using a polygon scanner. Meanwhile, we significantly improve the signal-to-noise ratio by employing a spatial-spectral residual learning network, reaching a level comparable to that with 100 times integration. Collectively, our system enables high-speed vibrational spectroscopic imaging of multiple biomolecules in samples ranging from a single live microbe to a tissue slice.Single-cell RNA sequencing combined with spatial information on landmark genes enables reconstruction of spatially-resolved tissue cell atlases. However, such approaches are challenging for rare cell types, since their mRNA contents are diluted in the spatial transcriptomics bulk measurements used for landmark gene detection. In the small intestine, enterocytes, the most common cell type, exhibit zonated expression programs along the crypt-villus axis, but zonation patterns of rare cell types such as goblet and tuft cells remain uncharacterized. https://www.selleckchem.com/products/ccs-1477-cbp-in-1-.html Here, we present ClumpSeq, an approach for sequencing small clumps of attached cells. By inferring the crypt-villus location of each clump from enterocyte landmark genes, we establish spatial atlases for all epithelial cell types in the small intestine. We identify elevated expression of immune-modulatory genes in villus tip goblet and tuft cells and heterogeneous migration patterns of enteroendocrine cells. ClumpSeq can be applied for reconstructing spatial atlases of rare cell types in other tissues and tumors.
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  • This study explored the general and oral health perceptions in the Venezuelan immigrant population in Medellín (Colombia) and its conditioning factors. A qualitative study involving Venezuelan immigrants ≥18 years with a minimum stay of six months in Colombia was conducted. Dentists, dental students, and other health professionals also participated. Semi-structured interviews (n = 17), focus groups (n = 2), and key informants' interviews (n = 4) were utilized. The interviews and focus groups were recorded and transcribed for later narrative content analysis. A high degree of vulnerability of participants was found due to the precarious living conditions from the premigratory moment and the lack of job placement possibilities at the time of settling in Colombia, where the migratory status played a fundamental role. Among the perceived needs, the mitigation of noncommunicable diseases stood out. Poor mental health symptoms (depression and anxiety) were perceived, and oral health was not a priority. Barriers to accessing health and dental care were found. The migrant condition was found to be a determinant that affected physical, mental, and oral health and the provision of health care. This situation is of interest to the construction of public health policies that guarantee access to fundamental rights.The response of plant N relations to the combination of elevated CO2 (eCO2) and warming are poorly understood. To study this, tomato (Solanum lycopersicum) plants were grown at 400 or 700 ppm CO2 and 33/28 or 38/33 °C (day/night), and their soil was labeled with 15NO3- or 15NH4+. Plant dry mass, root N-uptake rate, root-to-shoot net N translocation, whole-plant N assimilation, and root resource availability (%C, %N, total nonstructural carbohydrates) were measured. Relative to eCO2 or warming alone, eCO2 + warming decreased growth, NO3- and NH4+-uptake rates, root-to-shoot net N translocation, and whole-plant N assimilation. Decreased N assimilation with eCO2 + warming was driven mostly by inhibition of NO3- assimilation, and was not associated with root resource limitations or damage to N-assimilatory proteins. Previously, we showed in tomato that eCO2 + warming decreases the concentration of N-uptake and -assimilatory proteins in roots, and dramatically increases leaf angle, which decreases whole-plant light capture and, hence, photosynthesis and growth. Thus, decreases in N uptake and assimilation with eCO2 + warming in tomato are likely due to reduced plant N demand.Filamentous anionic polyelectrolytes are common in biological materials. Some examples are the cytoskeletal filaments that assemble into networks and bundled structures to give the cell mechanical resistance and that act as surfaces on which enzymes and other molecules can dock. Some viruses, especially bacteriophages are also long thin polyelectrolytes, and their bending stiffness is similar to those of the intermediate filament class of cytoskeletal polymers. These relatively stiff, thin, and long polyelectrolytes have charge densities similar to those of more flexible polyelectrolytes such as DNA, hyaluronic acid, and polyacrylates, and they can form interpenetrating networks and viscoelastic gels at volume fractions far below those at which more flexible polymers form hydrogels. In this report, we examine how different types of divalent and multivalent counterions interact with two biochemically different but physically similar filamentous polyelectrolytes Pf1 virus and vimentin intermediate filaments (VIF). Different divalent cations aggregate both polyelectrolytes similarly, but transition metal ions are more efficient than alkaline earth ions and their efficiency increases with increasing atomic weight. Comparison of these two different types of polyelectrolyte filaments enables identification of general effects of counterions with polyelectrolytes and can identify cases where the interaction of the counterions and the filaments exhibits stronger and more specific interactions than those of counterion condensation.In this work, electroluminescence in Metal-Insulator-Semiconductors (MIS) and Metal-Insulator-Metal (MIM)-type structures was studied. These structures were fabricated with single- and double-layer silicon-rich-oxide (SRO) films by means of Hot Filament Chemical Vapor Deposition (HFCVD), gold and indium tin oxide (ITO) were used on silicon and quartz substrates as a **** and front contact, respectively. The thickness, refractive indices, and excess silicon of the SRO films were analyzed. The behavior of the MIS and MIM-type structures and the effects of the pristine current-voltage (I-V) curves with high and low conduction states are presented. https://www.selleckchem.com/products/c75.html The structures exhibit different conduction mechanisms as the Ohmic, Poole-Frenkel, Fowler-Nordheim, and Hopping that contribute to carrier transport in the SRO films. These conduction mechanisms are related to the electroluminescence spectra obtained from the MIS and MIM-like structures with SRO films. The electroluminescence present in these structures has shown bright dots in the low current of 36 uA with a voltage of -20 V to -50 V. However, when applied voltages greater than -67 V with 270 uA, a full area with uniform blue light emission is shown.In contrast to motor symptoms, non-motor symptoms in Parkinson's disease (PD) are often poorly recognized and inadequately treated. Fatigue is one of the most common non-motor symptoms in PD and affects a broad range of everyday activities, causes disability, and substantially reduces the quality of life. It occurs at every stage of PD, and once present, it often persists and worsens over time. PD patients attending the 2013 World Parkinson Congress voted fatigue as the leading symptom in need of further research. However, despite its clinical significance, little progress has been made in understanding the causes of Parkinson's disease-related fatigue (PDRF) and developing effective treatment options, which argues strongly for a greater effort. Transcranial direct current stimulation (tDCS) is a technique to non-invasively modulate cortical excitability by delivering low electrical currents to the cerebral cortex. In the past, it has been consistently evidenced that tDCS has the ability to induce neuromodulatory changes in the motor, sensory, and cognitive domains.
    This study explored the general and oral health perceptions in the Venezuelan immigrant population in Medellín (Colombia) and its conditioning factors. A qualitative study involving Venezuelan immigrants ≥18 years with a minimum stay of six months in Colombia was conducted. Dentists, dental students, and other health professionals also participated. Semi-structured interviews (n = 17), focus groups (n = 2), and key informants' interviews (n = 4) were utilized. The interviews and focus groups were recorded and transcribed for later narrative content analysis. A high degree of vulnerability of participants was found due to the precarious living conditions from the premigratory moment and the lack of job placement possibilities at the time of settling in Colombia, where the migratory status played a fundamental role. Among the perceived needs, the mitigation of noncommunicable diseases stood out. Poor mental health symptoms (depression and anxiety) were perceived, and oral health was not a priority. Barriers to accessing health and dental care were found. The migrant condition was found to be a determinant that affected physical, mental, and oral health and the provision of health care. This situation is of interest to the construction of public health policies that guarantee access to fundamental rights.The response of plant N relations to the combination of elevated CO2 (eCO2) and warming are poorly understood. To study this, tomato (Solanum lycopersicum) plants were grown at 400 or 700 ppm CO2 and 33/28 or 38/33 °C (day/night), and their soil was labeled with 15NO3- or 15NH4+. Plant dry mass, root N-uptake rate, root-to-shoot net N translocation, whole-plant N assimilation, and root resource availability (%C, %N, total nonstructural carbohydrates) were measured. Relative to eCO2 or warming alone, eCO2 + warming decreased growth, NO3- and NH4+-uptake rates, root-to-shoot net N translocation, and whole-plant N assimilation. Decreased N assimilation with eCO2 + warming was driven mostly by inhibition of NO3- assimilation, and was not associated with root resource limitations or damage to N-assimilatory proteins. Previously, we showed in tomato that eCO2 + warming decreases the concentration of N-uptake and -assimilatory proteins in roots, and dramatically increases leaf angle, which decreases whole-plant light capture and, hence, photosynthesis and growth. Thus, decreases in N uptake and assimilation with eCO2 + warming in tomato are likely due to reduced plant N demand.Filamentous anionic polyelectrolytes are common in biological materials. Some examples are the cytoskeletal filaments that assemble into networks and bundled structures to give the cell mechanical resistance and that act as surfaces on which enzymes and other molecules can dock. Some viruses, especially bacteriophages are also long thin polyelectrolytes, and their bending stiffness is similar to those of the intermediate filament class of cytoskeletal polymers. These relatively stiff, thin, and long polyelectrolytes have charge densities similar to those of more flexible polyelectrolytes such as DNA, hyaluronic acid, and polyacrylates, and they can form interpenetrating networks and viscoelastic gels at volume fractions far below those at which more flexible polymers form hydrogels. In this report, we examine how different types of divalent and multivalent counterions interact with two biochemically different but physically similar filamentous polyelectrolytes Pf1 virus and vimentin intermediate filaments (VIF). Different divalent cations aggregate both polyelectrolytes similarly, but transition metal ions are more efficient than alkaline earth ions and their efficiency increases with increasing atomic weight. Comparison of these two different types of polyelectrolyte filaments enables identification of general effects of counterions with polyelectrolytes and can identify cases where the interaction of the counterions and the filaments exhibits stronger and more specific interactions than those of counterion condensation.In this work, electroluminescence in Metal-Insulator-Semiconductors (MIS) and Metal-Insulator-Metal (MIM)-type structures was studied. These structures were fabricated with single- and double-layer silicon-rich-oxide (SRO) films by means of Hot Filament Chemical Vapor Deposition (HFCVD), gold and indium tin oxide (ITO) were used on silicon and quartz substrates as a back and front contact, respectively. The thickness, refractive indices, and excess silicon of the SRO films were analyzed. The behavior of the MIS and MIM-type structures and the effects of the pristine current-voltage (I-V) curves with high and low conduction states are presented. https://www.selleckchem.com/products/c75.html The structures exhibit different conduction mechanisms as the Ohmic, Poole-Frenkel, Fowler-Nordheim, and Hopping that contribute to carrier transport in the SRO films. These conduction mechanisms are related to the electroluminescence spectra obtained from the MIS and MIM-like structures with SRO films. The electroluminescence present in these structures has shown bright dots in the low current of 36 uA with a voltage of -20 V to -50 V. However, when applied voltages greater than -67 V with 270 uA, a full area with uniform blue light emission is shown.In contrast to motor symptoms, non-motor symptoms in Parkinson's disease (PD) are often poorly recognized and inadequately treated. Fatigue is one of the most common non-motor symptoms in PD and affects a broad range of everyday activities, causes disability, and substantially reduces the quality of life. It occurs at every stage of PD, and once present, it often persists and worsens over time. PD patients attending the 2013 World Parkinson Congress voted fatigue as the leading symptom in need of further research. However, despite its clinical significance, little progress has been made in understanding the causes of Parkinson's disease-related fatigue (PDRF) and developing effective treatment options, which argues strongly for a greater effort. Transcranial direct current stimulation (tDCS) is a technique to non-invasively modulate cortical excitability by delivering low electrical currents to the cerebral cortex. In the past, it has been consistently evidenced that tDCS has the ability to induce neuromodulatory changes in the motor, sensory, and cognitive domains.
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  • We investigated the combined effect of chitosan (CHT) and putrescine (PUT) on the postharvest shelf life of Capsicum fruit concerning the metabolism of reactive oxygen species (ROS) through direct and indirect effects on ripening characters cell wall hydrolyzing enzyme and ROS metabolism. The PUT and CHT directly affected quality indices like color, firmness and water loss with a concomitant oxidative bust in the development of O2•- and H2O2 in fruit pulp. This was accompanied by significant suppression of respiratory flux, a decrease of total soluble solids and ascorbic acid content throughout postharvest storage. PUT applied with CHT modified the oxidative metabolism of fruits by a significant reduction in the level of O2•- and H2O2 content. In addition, a significant accumulation of total polyamine under respective treatment was reasonably correlated with both ROS producing enzyme as well as H2O2 and O2•-. Wall hydrolyzing enzymes like pectin methyl esterase and cellulase had marked downregulation both under PUT and CHT + PUT treatment. Moreover, on close observation, the combinational effects of PUT and CHT had better effects in the regulation of those enzymes as compared to individual treatment. Fruits restore higher antioxidative capacities as evident with superoxide dismutase (***), guaiacol peroxidases (GPX), ascorbate peroxidase (APX) catalase (CAT), glutathione peroxidase (GPX), NADPH oxidase (NOX) and glutathione reductase (GR), indicating their roles on fruit coat softening. Finally, the treatment of PUT and CHT in combination increased shelf life vis-à-vis the quality of fruit.We investigated the within- and between-leaf variability in the carbon and nitrogen isotope composition (δ13C and δ15N) and total nitrogen (TN) content in two grapevine cultivars (Vitis vinifera cv. Chasselas and Pinot noir) field-grown under rain-fed conditions. The within-leaf variability was studied in discs sampled from base-to-tip and left and right regions from the margin to midrib. The intra- and interplant variability was studied by comparing leaves at different positions along the shoot (basal, median, apical). https://www.selleckchem.com/products/ono-7300243.html In leaves from both cultivars, a decrease in δ13C from base to tip was observed, which is in line with an upward gradient of stomatal density and chlorophyll concentration. Less important, but still significant differences were observed between the right and left discs. The leaf TN and δ15N values differed between cultivars, showed smaller variations than the δ13C values, and no systematic spatial trends. The intraleaf variations in δ13C, δ15N, and TN suggest that stomatal behavior, CO2 fixation, chlorophyll concentrations, and the chemical composition of leaf components were heterogeneous in the leaves. At the canopy scale, the apical leaves had less 13C and more 15N and TN than the basal leaves, indicating differences in their photosynthetic capacity and remobilizations from old, senescing leaves to younger leaves. Overall, this study demonstrates patchiness in the δ13C and δ15N values of grapevine leaves and species-specificity of the nitrogen assimilation and 15N fractionation. These findings suggest that care must be taken not to overinterpret foliar δ13C and δ15N values in studies based on fragmented material as markers of physiological and biochemical responses to environmental factors.Thaumatin-like proteins (TLPs) are pathogenesis-related (PR5) proteins, which are induced in response to various biotic and abiotic stresses. The present work was carried out to clone TLP of Camellia sinensis (CsTLP) and to evaluate the response of transgenic lines of Arabidopsis constitutively expressing CsTLP under drought conditions. Data showed that transgenic lines exhibited lower relative electrolyte leakage and higher water retention capacity as compared to the wild-type (WT) plants under drought stress. In addition, results with confocal microscopy showed CsTLP + GFP fusion protein to be localized in the cell membrane which moved to the intercellular spaces under prolonged drought stress. Expression of CsTLP enhanced seed yield and the plant survival in transgenic lines as compared to the WT plants under drought stress. Results suggested the importance of CsTLP in improving drought tolerance in Arabidopsis.NAC (NAM, ATAF1/2 and CUC2) transcription factors play critical roles in plant development and abiotic stress responses, and aquaporins have diverse functions in environmental stress responses. In this study, we described the salt-induced transcriptional responses of ThNAC12 and ThPIP2;5 in Tamarix hispida, and their regulatory mechanisms in response to salt stress. Using yeast one-hybrid (Y1H), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays, we identified that ThNAC12 directly binds to the NAC recognition sequence (NACRS) of the ThPIP2;5 promoter and then activates the ThPIP2;5 expression. Subcellular localization and transcriptional activation assays demonstrated that ThNAC12 was a nuclear protein with a C-terminal transactivation domain. Compared with the corresponding control plants, transgenic plants overexpressing ThNAC12 exhibited enhanced salt tolerance and displayed increased reactive oxygen species (ROS) scavenging capability and antioxidant enzyme activity levels under salt stress. All results suggested that overexpression of ThNAC12 in plants enhanced salt tolerance through modulation of ROS scavenging via direct regulation of ThPIP2;5 expression in T. hispida.
    Systemic Lupus Erythematous is a systemic autoimmune disease with multiorgan inflammation. Clinical manifestations are variable and may involve the Central Nervous System. Acute transverse myelitis is a rare complication. Recent studies have shown an association between SLE, transverse myelitis and presence of anti-aquaporin 4 antibodies.

    We describe the case of an 80-year-old woman with a subacute onset of right hemiplegia followed by left-sided ataxia. Cervical MRI revealed longitudinally extensive transverse myelitis. Blood examinations showed positivity for anti-nuclear antibodies, anti-double-stranded DNA antibodies, anti-phospholipid antibodies and anti-aquaporin 4 antibodies.

    Anti-aquaporin 4 antibody testing is of paramount importance in order to reach a correct diagnosis and to treat patients with the best therapeutic approach.
    Anti-aquaporin 4 antibody testing is of paramount importance in order to reach a correct diagnosis and to treat patients with the best therapeutic approach.
    We investigated the combined effect of chitosan (CHT) and putrescine (PUT) on the postharvest shelf life of Capsicum fruit concerning the metabolism of reactive oxygen species (ROS) through direct and indirect effects on ripening characters cell wall hydrolyzing enzyme and ROS metabolism. The PUT and CHT directly affected quality indices like color, firmness and water loss with a concomitant oxidative bust in the development of O2•- and H2O2 in fruit pulp. This was accompanied by significant suppression of respiratory flux, a decrease of total soluble solids and ascorbic acid content throughout postharvest storage. PUT applied with CHT modified the oxidative metabolism of fruits by a significant reduction in the level of O2•- and H2O2 content. In addition, a significant accumulation of total polyamine under respective treatment was reasonably correlated with both ROS producing enzyme as well as H2O2 and O2•-. Wall hydrolyzing enzymes like pectin methyl esterase and cellulase had marked downregulation both under PUT and CHT + PUT treatment. Moreover, on close observation, the combinational effects of PUT and CHT had better effects in the regulation of those enzymes as compared to individual treatment. Fruits restore higher antioxidative capacities as evident with superoxide dismutase (SOD), guaiacol peroxidases (GPX), ascorbate peroxidase (APX) catalase (CAT), glutathione peroxidase (GPX), NADPH oxidase (NOX) and glutathione reductase (GR), indicating their roles on fruit coat softening. Finally, the treatment of PUT and CHT in combination increased shelf life vis-à-vis the quality of fruit.We investigated the within- and between-leaf variability in the carbon and nitrogen isotope composition (δ13C and δ15N) and total nitrogen (TN) content in two grapevine cultivars (Vitis vinifera cv. Chasselas and Pinot noir) field-grown under rain-fed conditions. The within-leaf variability was studied in discs sampled from base-to-tip and left and right regions from the margin to midrib. The intra- and interplant variability was studied by comparing leaves at different positions along the shoot (basal, median, apical). https://www.selleckchem.com/products/ono-7300243.html In leaves from both cultivars, a decrease in δ13C from base to tip was observed, which is in line with an upward gradient of stomatal density and chlorophyll concentration. Less important, but still significant differences were observed between the right and left discs. The leaf TN and δ15N values differed between cultivars, showed smaller variations than the δ13C values, and no systematic spatial trends. The intraleaf variations in δ13C, δ15N, and TN suggest that stomatal behavior, CO2 fixation, chlorophyll concentrations, and the chemical composition of leaf components were heterogeneous in the leaves. At the canopy scale, the apical leaves had less 13C and more 15N and TN than the basal leaves, indicating differences in their photosynthetic capacity and remobilizations from old, senescing leaves to younger leaves. Overall, this study demonstrates patchiness in the δ13C and δ15N values of grapevine leaves and species-specificity of the nitrogen assimilation and 15N fractionation. These findings suggest that care must be taken not to overinterpret foliar δ13C and δ15N values in studies based on fragmented material as markers of physiological and biochemical responses to environmental factors.Thaumatin-like proteins (TLPs) are pathogenesis-related (PR5) proteins, which are induced in response to various biotic and abiotic stresses. The present work was carried out to clone TLP of Camellia sinensis (CsTLP) and to evaluate the response of transgenic lines of Arabidopsis constitutively expressing CsTLP under drought conditions. Data showed that transgenic lines exhibited lower relative electrolyte leakage and higher water retention capacity as compared to the wild-type (WT) plants under drought stress. In addition, results with confocal microscopy showed CsTLP + GFP fusion protein to be localized in the cell membrane which moved to the intercellular spaces under prolonged drought stress. Expression of CsTLP enhanced seed yield and the plant survival in transgenic lines as compared to the WT plants under drought stress. Results suggested the importance of CsTLP in improving drought tolerance in Arabidopsis.NAC (NAM, ATAF1/2 and CUC2) transcription factors play critical roles in plant development and abiotic stress responses, and aquaporins have diverse functions in environmental stress responses. In this study, we described the salt-induced transcriptional responses of ThNAC12 and ThPIP2;5 in Tamarix hispida, and their regulatory mechanisms in response to salt stress. Using yeast one-hybrid (Y1H), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays, we identified that ThNAC12 directly binds to the NAC recognition sequence (NACRS) of the ThPIP2;5 promoter and then activates the ThPIP2;5 expression. Subcellular localization and transcriptional activation assays demonstrated that ThNAC12 was a nuclear protein with a C-terminal transactivation domain. Compared with the corresponding control plants, transgenic plants overexpressing ThNAC12 exhibited enhanced salt tolerance and displayed increased reactive oxygen species (ROS) scavenging capability and antioxidant enzyme activity levels under salt stress. All results suggested that overexpression of ThNAC12 in plants enhanced salt tolerance through modulation of ROS scavenging via direct regulation of ThPIP2;5 expression in T. hispida. Systemic Lupus Erythematous is a systemic autoimmune disease with multiorgan inflammation. Clinical manifestations are variable and may involve the Central Nervous System. Acute transverse myelitis is a rare complication. Recent studies have shown an association between SLE, transverse myelitis and presence of anti-aquaporin 4 antibodies. We describe the case of an 80-year-old woman with a subacute onset of right hemiplegia followed by left-sided ataxia. Cervical MRI revealed longitudinally extensive transverse myelitis. Blood examinations showed positivity for anti-nuclear antibodies, anti-double-stranded DNA antibodies, anti-phospholipid antibodies and anti-aquaporin 4 antibodies. Anti-aquaporin 4 antibody testing is of paramount importance in order to reach a correct diagnosis and to treat patients with the best therapeutic approach. Anti-aquaporin 4 antibody testing is of paramount importance in order to reach a correct diagnosis and to treat patients with the best therapeutic approach.
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  • 73, 95% CI 0.71-0.96). No significant association between smoking and PAL was found for boys. Results suggest that adolescent boys and girls do not follow the equal trajectories when it comes to relationships between smoking and PAL. Conclusions In developing promotional public health actions related to a decrease of smoking and increase of PAL, a gender-specific approach is highly recommended. Further studies analyzing the cause-effect relationship between consumption of other types of psychoactive substances and PAL in this age group are warranted.Even though urban green spaces may host a relatively high diversity of wild bees, urban environments impact the pollinator taxonomic and functional diversity in a way that is still misunderstood. Here, we provide an assessment of the taxonomic and functional composition of pollinator assemblages and their response to urbanization in the Paris region (France). We performed a spring-to-fall survey of insect pollinators in green spaces embedded in a dense urban matrix and in rural grasslands, using a plant setup standardized across sites and throughout the seasons. We compared pollinator species composition and the occurrence of bee functional traits over the two habitats. There was no difference in species richness between habitats, though urban assemblages were dominated by very abundant generalist species and displayed a lower evenness. They also included fewer brood parasitic, solitary or ground-nesting bees. Overall, bees tended to be larger in the city than in the semi-natural grasslands, and this trait exhibited seasonal variations. The urban environment filters out some life history traits of insect pollinators and alters their seasonal patterns, likely as a result of the fragmentation and scarcity of feeding and nesting resources. This could have repercussions on pollination networks and the efficiency of the pollination function.Functional coatings for application on surfaces are of growing interest. Especially in the textile industry, durable water and oil repellent finishes are of special demand for implementation in the outdoor sector, but also as safety-protection clothes against oil or chemicals. Such oil and chemical repellent textiles can be achieved by coating surfaces with fluoropolymers. As many concerns exist regarding (per)fluorinated polymers due to their high persistence and accumulation capacity in the environment, a durable and resistant coating is essential also during the washing processes of textiles. Within the present study, different strategies are examined for a durable resistant cross-linking of a novel fluoropolymer on the surface of fibers. The monomer 2-((1,1,2-trifluoro-2-(perfluoropropoxy)ethyl)thio)ethyl acrylate, whose fluorinated side-chain is degradable by treatment with ozone, was used for this purpose. The polymers were synthesized via free radical polymerization in emulsion, and different amounts of cross-linking reagents were copolymerized. The final polymer dispersions were applied to cellulose fibers and the cross-linking was induced thermally or by irradiation with UV-light. In order to investigate the cross-linking efficiency, tensile elongation studies were carried out. In addition, multiple washing processes of the fibers was performed and the polymer loss during washing, as well as the effects on oil and water repellency were investigated. https://www.selleckchem.com/products/fx11.html The cross-linking strategy paves the way to a durable fluoropolymer-based functional coating and the polymers are expected to provide a promising and sustainable alternative to functional coatings.Lupus nephritis (LN) is an inflammatory renal disease of patients with systemic lupus erythematosus with lots of immune complexes deposited in kidneys. Accumulated studies have demonstrated the close relationships among dyslipidaemia, inflammation, and autoimmune response, and oxidative stress in the patients. Lipids play numerous important roles in biological process and cellular functions. Herein, shotgun lipidomics was employed to quantitatively analyze cellular lipidomes in the renal tissue of MRL/lpr **** in the progression of LN (including pre-LN and LN state) with/without treated with glucocorticoids (GCs). The levels of cytokines (i.e., TNF-α (Tumor necrosis factor alpha) and IL-6 (Interleukin 6)) in the serum were measured by ELISA (enzyme-linked immunosorbent assay) kits. Renal histopathological changes and C3 deposition in the glomeruli of the **** were also determined. Lipidomics analysis revealed that the ectopic fat deposition and the aberrant metabolism of lipids that were relevant to oxidative stress (e.g., 4-hydroxyalkenal, ceramide, lysophospholipid species, etc.) always existed in the development of LN. Moreover, the anti-inflammatory FAHFA (fatty acid ester of hydroxyl fatty acid) species in the kidney tissue could largely reflect the severity of LN. Thus, they were a potential early biomarker for LN. In addition, the study also revealed that treatment with GCs could prevent the progression of LN, but greatly aggravate the aberrant metabolism of the lipids, particularly when used for a long time.In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine-benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1-BBD14 compounds' antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir.To discover new compounds with broad spectrum and high activity, we designed a series of novel benzamides containing 1,2,4-oxadiazole moiety by bioisosterism, and 28 benzamides derivatives with antifungal activity were synthesized. These compounds were evaluated against four fungi Botrytis cinereal, FusaHum graminearum, Marssonina mali, and Thanatephorus cucumeris. The results indicated that most of the compounds displayed good fungicidal activities, especially against Botrytis cinereal. For example, 10a (84.4%), 10d (83.6%), 10e (83.3%), 10f (83.1%), 10i (83.3%), and 10l (83.6%) were better than pyraclostrobin (81.4%) at 100 mg/L. In addition, the acute toxicity of 10f to zebrafish embryo was 20.58 mg/L, which was classified as a low-toxicity compound.
    73, 95% CI 0.71-0.96). No significant association between smoking and PAL was found for boys. Results suggest that adolescent boys and girls do not follow the equal trajectories when it comes to relationships between smoking and PAL. Conclusions In developing promotional public health actions related to a decrease of smoking and increase of PAL, a gender-specific approach is highly recommended. Further studies analyzing the cause-effect relationship between consumption of other types of psychoactive substances and PAL in this age group are warranted.Even though urban green spaces may host a relatively high diversity of wild bees, urban environments impact the pollinator taxonomic and functional diversity in a way that is still misunderstood. Here, we provide an assessment of the taxonomic and functional composition of pollinator assemblages and their response to urbanization in the Paris region (France). We performed a spring-to-fall survey of insect pollinators in green spaces embedded in a dense urban matrix and in rural grasslands, using a plant setup standardized across sites and throughout the seasons. We compared pollinator species composition and the occurrence of bee functional traits over the two habitats. There was no difference in species richness between habitats, though urban assemblages were dominated by very abundant generalist species and displayed a lower evenness. They also included fewer brood parasitic, solitary or ground-nesting bees. Overall, bees tended to be larger in the city than in the semi-natural grasslands, and this trait exhibited seasonal variations. The urban environment filters out some life history traits of insect pollinators and alters their seasonal patterns, likely as a result of the fragmentation and scarcity of feeding and nesting resources. This could have repercussions on pollination networks and the efficiency of the pollination function.Functional coatings for application on surfaces are of growing interest. Especially in the textile industry, durable water and oil repellent finishes are of special demand for implementation in the outdoor sector, but also as safety-protection clothes against oil or chemicals. Such oil and chemical repellent textiles can be achieved by coating surfaces with fluoropolymers. As many concerns exist regarding (per)fluorinated polymers due to their high persistence and accumulation capacity in the environment, a durable and resistant coating is essential also during the washing processes of textiles. Within the present study, different strategies are examined for a durable resistant cross-linking of a novel fluoropolymer on the surface of fibers. The monomer 2-((1,1,2-trifluoro-2-(perfluoropropoxy)ethyl)thio)ethyl acrylate, whose fluorinated side-chain is degradable by treatment with ozone, was used for this purpose. The polymers were synthesized via free radical polymerization in emulsion, and different amounts of cross-linking reagents were copolymerized. The final polymer dispersions were applied to cellulose fibers and the cross-linking was induced thermally or by irradiation with UV-light. In order to investigate the cross-linking efficiency, tensile elongation studies were carried out. In addition, multiple washing processes of the fibers was performed and the polymer loss during washing, as well as the effects on oil and water repellency were investigated. https://www.selleckchem.com/products/fx11.html The cross-linking strategy paves the way to a durable fluoropolymer-based functional coating and the polymers are expected to provide a promising and sustainable alternative to functional coatings.Lupus nephritis (LN) is an inflammatory renal disease of patients with systemic lupus erythematosus with lots of immune complexes deposited in kidneys. Accumulated studies have demonstrated the close relationships among dyslipidaemia, inflammation, and autoimmune response, and oxidative stress in the patients. Lipids play numerous important roles in biological process and cellular functions. Herein, shotgun lipidomics was employed to quantitatively analyze cellular lipidomes in the renal tissue of MRL/lpr mice in the progression of LN (including pre-LN and LN state) with/without treated with glucocorticoids (GCs). The levels of cytokines (i.e., TNF-α (Tumor necrosis factor alpha) and IL-6 (Interleukin 6)) in the serum were measured by ELISA (enzyme-linked immunosorbent assay) kits. Renal histopathological changes and C3 deposition in the glomeruli of the mice were also determined. Lipidomics analysis revealed that the ectopic fat deposition and the aberrant metabolism of lipids that were relevant to oxidative stress (e.g., 4-hydroxyalkenal, ceramide, lysophospholipid species, etc.) always existed in the development of LN. Moreover, the anti-inflammatory FAHFA (fatty acid ester of hydroxyl fatty acid) species in the kidney tissue could largely reflect the severity of LN. Thus, they were a potential early biomarker for LN. In addition, the study also revealed that treatment with GCs could prevent the progression of LN, but greatly aggravate the aberrant metabolism of the lipids, particularly when used for a long time.In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine-benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1-BBD14 compounds' antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir.To discover new compounds with broad spectrum and high activity, we designed a series of novel benzamides containing 1,2,4-oxadiazole moiety by bioisosterism, and 28 benzamides derivatives with antifungal activity were synthesized. These compounds were evaluated against four fungi Botrytis cinereal, FusaHum graminearum, Marssonina mali, and Thanatephorus cucumeris. The results indicated that most of the compounds displayed good fungicidal activities, especially against Botrytis cinereal. For example, 10a (84.4%), 10d (83.6%), 10e (83.3%), 10f (83.1%), 10i (83.3%), and 10l (83.6%) were better than pyraclostrobin (81.4%) at 100 mg/L. In addition, the acute toxicity of 10f to zebrafish embryo was 20.58 mg/L, which was classified as a low-toxicity compound.
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  • This novel graft with dual modifications shows promising as a new small-diameter vascular graft. This study provides a guidance for promoting endothelialization and blood compatibility by dual modifications of biomimetic structure and immobilized bioactive molecules.Here, we study the effect of hierarchical and one-dimensional (1D) metal oxide nanorods (H-NRs) such as γ-Al2O3, β-MnO2, and ZnO as microbial inhibitors on the antimicrobial efficiency in aqueous solution. These microbial inhibitors are fabricated in a diverse range of nanoscale hierarchical morphologies and geometrical shapes that have effective surface exposure, and well-defined 1D orientation. For instance, γ-Al2O3 H-NRs with 20 nm width and Ë‚0.5 μm length are grown dominantly in the [400] direction. The wurtzite structures of β-MnO2 H-NRs with 30 nm width and 0.5-1 μm length are preferentially oriented in the [100] direction. Longitudinal H-NRs with a width of 40 nm and length of 1 μm are controlled with ZnO wurtzite structure and grown in [0001] direction. The antimicrobial efficiency of H-NRs was evaluated through experimental assays using a set of microorganisms (Gram-positive Staphylococcus aureus, Bacillus thuriginesis, and Bacillus subtilis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. Minimal inhibitory and minimum bactericidal concentrations (****and MBC) were determined. These 1D H-NRs exhibited antibacterial activity against all the used strains. The active surface exposure sites of H-NRs play a key role in the strong interaction with the thiol units of vital bacterial enzymes, leading to microbial inactivation. Our finding indicates that the biological effect of the H-NR surface planes on microbial inhibition is decreased in the order of [400]-γ-Al2O3 > [100]-β-MnO2 > [0001]-ZnO geometrics. The lowest key values including MIC (1.146 and 0.250 μg/mL), MBC (1.146, 0.313 μg/mL), and ****MFC (0.375 and 0.375 μg/mL) are achieved for [400]-plane γ-Al2O3 surfaces when tested against Gram-positive and -negative bacteria, respectively. Among the three H-NRs, the smallest diameter size and length, the largest surface area, and the active exposure [400] direction of γ-Al2O3 H-NRs could provide the highest microbial inactivation.Osteoporosis (OP) is a significant public health problem with associated fragility fractures, thereby causing large bone defects and difficulty in self-repair. The introduction of human mesenchymal stem cells (hMSCs) is the most promising platform in bone tissue engineering for OP therapy, which induces less side effects than conventional medication. However, the safety and efficiency of the cell-based OP therapy requires the ability to monitor the cell's outcome and biodistribution after cell transplantation. Therefore, we designed an in vivo system to track hMSCs in real time and simultaneously attempted to obtain a significant therapeutic effect during the bone repair process. In this study, we synthesized Ir(III) complex, followed by encapsulation with biodegradable methoxy-poly(ethylene glycol) poly(lactic-co-glycolic acid) nanospheres through double emulsions strategy. The Ir(III) complex nanospheres did not affect hMSC proliferation, stemness, and differentiation and realized highly efficient and long-term cellular labeling for at least 25 days in vivo. The optimal transplantation conditions were also determined first by injecting a gradient number of labeled hMSCs percutaneously into the cranial defect of the nude mouse model. Next, we applied this method to ovariectomy-induced OP ****. Results showed long-term optical imaging with high fluorescence intensity and computed tomography (CT) scanning with significantly increased bone formation between the osteoporotic and sham-operated bones. During the tracking process, two **** from each group were sacrificed at two representative time points to examine the bony defect bridging via micro-CT morphometric analyses. Our data showed remarkable promise for efficient hMSC tracking and encouraging treatment in bioimaging-guided OP stem cell therapy.The management of respiratory diseases relies on the daily administration of multiple active pharmaceutical ingredients (APIs), leading to a lack of patient compliance and impaired quality of life. The frequency and dosage of the APIs result in increased side effects that further worsens the overall patient condition. Here, the manufacture of polymer-polymer core-shell microparticles for the sequential delivery of multiple APIs by inhalation delivery is reported. The microparticles, composed of biodegradable polymers silk fibroin (shell) and poly(L-lactic acid) (core), incorporating ciprofloxacin in the silk layer and ibuprofen (PLLA core) as the antibiotic and anti-inflammatory model APIs, respectively. The polymer-polymer core-shell structure and the spatial distribution of the APIs have been characterized using cutting-edge synchrotron macro ATR-FTIR technique, which was correlated with the respective API sequential release profiles. The APIs microparticles had a suitable size and aerosol properties for inhalation therapies (≤4.94 ± 0.21μm), with low cytotoxicity and immunogenicity in healthy lung epithelial cells. The APIs compartmentalization obtained by the microparticles not only could inhibit potential actives interactions but can provide modulation of the APIs release profiles via an inhalable single administration.Genomic deoxyribonucleic acid (DNA) stores and carries the information required to maintain and replicate cellular life. While **** efforts have been devoted in decoding the sequence of DNA basis to detect the genetic mutations related to cancer disease, it is becoming clear that physical properties, like structural conformation, stiffness and shape, can play an important role to recognize DNA modifications. https://www.selleckchem.com/products/sr59230a.html Here, silver-coated silicon nanowires (Ag/SiNWs) are exploited as Raman spectroscopic platform to easily discriminate healthy and cancer genomic DNA, extracted from human normal skin and malignant melanoma cells, respectively. In particular, aqueous DNA droplets are directly deposited onto a forest of Ag/SiNWs and Raman maps are acquired after sample dehydration. By applying principal component analysis (PCA) to the Raman spectra collected within the droplets, healthy and cancer cell DNA can be distinguished without false negative identifications and with few false positive results ( less then 2%). The discrimination occurs regardless the analysis of specific DNA sequencing, but through Raman bands strictly related to the interfacing of the DNA and the NWs.
    This novel graft with dual modifications shows promising as a new small-diameter vascular graft. This study provides a guidance for promoting endothelialization and blood compatibility by dual modifications of biomimetic structure and immobilized bioactive molecules.Here, we study the effect of hierarchical and one-dimensional (1D) metal oxide nanorods (H-NRs) such as γ-Al2O3, β-MnO2, and ZnO as microbial inhibitors on the antimicrobial efficiency in aqueous solution. These microbial inhibitors are fabricated in a diverse range of nanoscale hierarchical morphologies and geometrical shapes that have effective surface exposure, and well-defined 1D orientation. For instance, γ-Al2O3 H-NRs with 20 nm width and Ë‚0.5 μm length are grown dominantly in the [400] direction. The wurtzite structures of β-MnO2 H-NRs with 30 nm width and 0.5-1 μm length are preferentially oriented in the [100] direction. Longitudinal H-NRs with a width of 40 nm and length of 1 μm are controlled with ZnO wurtzite structure and grown in [0001] direction. The antimicrobial efficiency of H-NRs was evaluated through experimental assays using a set of microorganisms (Gram-positive Staphylococcus aureus, Bacillus thuriginesis, and Bacillus subtilis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. Minimal inhibitory and minimum bactericidal concentrations (MIC and MBC) were determined. These 1D H-NRs exhibited antibacterial activity against all the used strains. The active surface exposure sites of H-NRs play a key role in the strong interaction with the thiol units of vital bacterial enzymes, leading to microbial inactivation. Our finding indicates that the biological effect of the H-NR surface planes on microbial inhibition is decreased in the order of [400]-γ-Al2O3 > [100]-β-MnO2 > [0001]-ZnO geometrics. The lowest key values including MIC (1.146 and 0.250 μg/mL), MBC (1.146, 0.313 μg/mL), and MIC/MFC (0.375 and 0.375 μg/mL) are achieved for [400]-plane γ-Al2O3 surfaces when tested against Gram-positive and -negative bacteria, respectively. Among the three H-NRs, the smallest diameter size and length, the largest surface area, and the active exposure [400] direction of γ-Al2O3 H-NRs could provide the highest microbial inactivation.Osteoporosis (OP) is a significant public health problem with associated fragility fractures, thereby causing large bone defects and difficulty in self-repair. The introduction of human mesenchymal stem cells (hMSCs) is the most promising platform in bone tissue engineering for OP therapy, which induces less side effects than conventional medication. However, the safety and efficiency of the cell-based OP therapy requires the ability to monitor the cell's outcome and biodistribution after cell transplantation. Therefore, we designed an in vivo system to track hMSCs in real time and simultaneously attempted to obtain a significant therapeutic effect during the bone repair process. In this study, we synthesized Ir(III) complex, followed by encapsulation with biodegradable methoxy-poly(ethylene glycol) poly(lactic-co-glycolic acid) nanospheres through double emulsions strategy. The Ir(III) complex nanospheres did not affect hMSC proliferation, stemness, and differentiation and realized highly efficient and long-term cellular labeling for at least 25 days in vivo. The optimal transplantation conditions were also determined first by injecting a gradient number of labeled hMSCs percutaneously into the cranial defect of the nude mouse model. Next, we applied this method to ovariectomy-induced OP mice. Results showed long-term optical imaging with high fluorescence intensity and computed tomography (CT) scanning with significantly increased bone formation between the osteoporotic and sham-operated bones. During the tracking process, two mice from each group were sacrificed at two representative time points to examine the bony defect bridging via micro-CT morphometric analyses. Our data showed remarkable promise for efficient hMSC tracking and encouraging treatment in bioimaging-guided OP stem cell therapy.The management of respiratory diseases relies on the daily administration of multiple active pharmaceutical ingredients (APIs), leading to a lack of patient compliance and impaired quality of life. The frequency and dosage of the APIs result in increased side effects that further worsens the overall patient condition. Here, the manufacture of polymer-polymer core-shell microparticles for the sequential delivery of multiple APIs by inhalation delivery is reported. The microparticles, composed of biodegradable polymers silk fibroin (shell) and poly(L-lactic acid) (core), incorporating ciprofloxacin in the silk layer and ibuprofen (PLLA core) as the antibiotic and anti-inflammatory model APIs, respectively. The polymer-polymer core-shell structure and the spatial distribution of the APIs have been characterized using cutting-edge synchrotron macro ATR-FTIR technique, which was correlated with the respective API sequential release profiles. The APIs microparticles had a suitable size and aerosol properties for inhalation therapies (≤4.94 ± 0.21μm), with low cytotoxicity and immunogenicity in healthy lung epithelial cells. The APIs compartmentalization obtained by the microparticles not only could inhibit potential actives interactions but can provide modulation of the APIs release profiles via an inhalable single administration.Genomic deoxyribonucleic acid (DNA) stores and carries the information required to maintain and replicate cellular life. While much efforts have been devoted in decoding the sequence of DNA basis to detect the genetic mutations related to cancer disease, it is becoming clear that physical properties, like structural conformation, stiffness and shape, can play an important role to recognize DNA modifications. https://www.selleckchem.com/products/sr59230a.html Here, silver-coated silicon nanowires (Ag/SiNWs) are exploited as Raman spectroscopic platform to easily discriminate healthy and cancer genomic DNA, extracted from human normal skin and malignant melanoma cells, respectively. In particular, aqueous DNA droplets are directly deposited onto a forest of Ag/SiNWs and Raman maps are acquired after sample dehydration. By applying principal component analysis (PCA) to the Raman spectra collected within the droplets, healthy and cancer cell DNA can be distinguished without false negative identifications and with few false positive results ( less then 2%). The discrimination occurs regardless the analysis of specific DNA sequencing, but through Raman bands strictly related to the interfacing of the DNA and the NWs.
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  • 04 (95% CI 1.00-1.11)) compared with the same-sex male twins. Second, in the female opposite-sex twins, we revealed a slightly higher, however, not statistically significant risk of depression (HR = 1.08 (95% CI 0.97-1.29)) or purchase of antidepressants (HR = 1.01 (95% CI 0.96-1.05)) when compared to the same-sex female twins.

    We found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life.
    We found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life.The molecular epidemiology of the virus and mapping helps understand the epidemics' evolution and apply quick control measures. This study provides genomic evidence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introductions into Sri Lanka and virus evolution during circulation. Whole-genome sequences of four SARS-CoV-2 strains obtained from coronavirus disease 2019 (COVID-19) positive patients reported in Sri Lanka during March 2020 were compared with sequences from Europe, Asia, Africa, Australia and North America. The phylogenetic analysis revealed that the sequence of the sample of the first local patient collected on 10 March, who contacted tourists from Italy, was clustered with SARS-CoV-2 strains collected from Italy, Germany, France and Mexico. Subsequently, the sequence of the isolate obtained on 19 March also clustered in the same group with the samples collected in March and April from Belgium, France, India and South Africa. The other two strains of SARS-CoV-2 were segregated from the main cluster, and the sample collected from 16 March clustered with England and the sample collected on 30 March showed the highest genetic divergence to the isolate of Wuhan, China. Here we report the first molecular epidemiological study conducted on circulating SARS-CoV-2 in Sri Lanka. The finding provides the robustness of molecular epidemiological tools and their application in tracing possible exposure in disease transmission during the pandemic.
    Impulsivity is a central symptom of borderline personality disorder (BPD) and its neural basis may be instantiated in a frontoparietal network involved in response inhibition. However, research has yet to determine whether neural activation differences in BPD associated with response inhibition are attributed to attentional saliency, which is subserved by a partially overlapping network of brain regions.

    Patients with BPD (n = 45) and 29 healthy controls (HCs; n = 29) underwent functional magnetic resonance imaging while completing a novel go/no-go task with infrequent odd-ball trials to control for attentional saliency. Contrasts reflecting a combination of response inhibition and attentional saliency (no-go > go), saliency processing alone (oddball > go), and response inhibition controlling for attentional saliency (no-go > oddball) were compared between BPD and HC.

    Compared to HC, BPD showed less activation in the combined no-go > go contrast in the right posterior inferior and middle-frocy or saliency alone, but no specific response inhibition neural activation difference when attentional saliency is controlled. The findings suggest a neural dysfunction in BPD underlying attention to salient or infrequent stimuli, which is supported by a negative correlation with self-rated impulsiveness.To identify sources of phenotypic heterogeneity in attention-deficit/hyperactivity disorder (ADHD) accounting for diversity in developmental/ pathogenic pathways, we examined, in a large sample of youth (N = 354), (a) associations between observed temperamental emotionality at age 3, an electrocortical index (i.e., reward positivity [RewP]) of initial responsiveness to reward at age 9, and ADHD symptoms at age 12, and (b) whether the association between emotionality and ADHD symptoms is mediated by initial responsiveness to reward. Bivariate analyses indicated greater positive emotionality (PE) was associated with enhanced RewP, lower age-9ADHD and lower age-12 inattention (IA). Negative emotionality (NE) was not associated with RewP or ADHD. Mediation analyses revealed the association between PE and hyperactivity/impulsivity (H/I) was mediated by RewP; enhanced RewP was associated with greater H/I. Greater PE was associated with enhanced RewP at a trend level. These effects held accounting for age-9 ADHD, age-12 IA and age-12 oppositional defiant and conduct disorder symptoms. https://www.selleckchem.com/products/fx11.html As such, preschool emotionality is associated with adolescent ADHD-H/I symptoms through late childhood initial responsiveness to reward. These relations indicate that individual differences in emotionality and reward responsiveness may be informative for personalizing ADHD interventions.Quantitative parameters for a two-state cooperative transition in duplex DNAs were finally obtained during the last 5 years. After a brief discussion of observations pertaining to the existence of the two-state equilibrium per se, the lengths, torsion, and bending elastic constants of the two states involved and the cooperativity parameter of the model are simply stated. Experimental tests of model predictions for the responses of DNA to small applied stretching, twisting, and bending stresses, and changes in temperature, ionic conditions, and sequence are described. The mechanism and significance of the large cooperativity, which enables significant DNA responses to such small perturbations, are also noted. The capacity of the model to resolve a number of long-standing and sometimes interconnected puzzles in the extant literature, including the origin of the broad pre-melting transition studied by numerous workers in the 1960s and 1970s, is demonstrated. Under certain conditions, the model predicts significant long-range attractive or repulsive interactions between hypothetical proteins with strong preferences for one or the other state that are bound to well-separated sites on the same DNA. A scenario is proposed for the activation of the ilvPG promoter on a supercoiled DNA by integration host factor.
    04 (95% CI 1.00-1.11)) compared with the same-sex male twins. Second, in the female opposite-sex twins, we revealed a slightly higher, however, not statistically significant risk of depression (HR = 1.08 (95% CI 0.97-1.29)) or purchase of antidepressants (HR = 1.01 (95% CI 0.96-1.05)) when compared to the same-sex female twins. We found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life. We found limited support for the hypothesis that prenatal exposure to testosterone was associated with the risk of depression later in life.The molecular epidemiology of the virus and mapping helps understand the epidemics' evolution and apply quick control measures. This study provides genomic evidence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) introductions into Sri Lanka and virus evolution during circulation. Whole-genome sequences of four SARS-CoV-2 strains obtained from coronavirus disease 2019 (COVID-19) positive patients reported in Sri Lanka during March 2020 were compared with sequences from Europe, Asia, Africa, Australia and North America. The phylogenetic analysis revealed that the sequence of the sample of the first local patient collected on 10 March, who contacted tourists from Italy, was clustered with SARS-CoV-2 strains collected from Italy, Germany, France and Mexico. Subsequently, the sequence of the isolate obtained on 19 March also clustered in the same group with the samples collected in March and April from Belgium, France, India and South Africa. The other two strains of SARS-CoV-2 were segregated from the main cluster, and the sample collected from 16 March clustered with England and the sample collected on 30 March showed the highest genetic divergence to the isolate of Wuhan, China. Here we report the first molecular epidemiological study conducted on circulating SARS-CoV-2 in Sri Lanka. The finding provides the robustness of molecular epidemiological tools and their application in tracing possible exposure in disease transmission during the pandemic. Impulsivity is a central symptom of borderline personality disorder (BPD) and its neural basis may be instantiated in a frontoparietal network involved in response inhibition. However, research has yet to determine whether neural activation differences in BPD associated with response inhibition are attributed to attentional saliency, which is subserved by a partially overlapping network of brain regions. Patients with BPD (n = 45) and 29 healthy controls (HCs; n = 29) underwent functional magnetic resonance imaging while completing a novel go/no-go task with infrequent odd-ball trials to control for attentional saliency. Contrasts reflecting a combination of response inhibition and attentional saliency (no-go > go), saliency processing alone (oddball > go), and response inhibition controlling for attentional saliency (no-go > oddball) were compared between BPD and HC. Compared to HC, BPD showed less activation in the combined no-go > go contrast in the right posterior inferior and middle-frocy or saliency alone, but no specific response inhibition neural activation difference when attentional saliency is controlled. The findings suggest a neural dysfunction in BPD underlying attention to salient or infrequent stimuli, which is supported by a negative correlation with self-rated impulsiveness.To identify sources of phenotypic heterogeneity in attention-deficit/hyperactivity disorder (ADHD) accounting for diversity in developmental/ pathogenic pathways, we examined, in a large sample of youth (N = 354), (a) associations between observed temperamental emotionality at age 3, an electrocortical index (i.e., reward positivity [RewP]) of initial responsiveness to reward at age 9, and ADHD symptoms at age 12, and (b) whether the association between emotionality and ADHD symptoms is mediated by initial responsiveness to reward. Bivariate analyses indicated greater positive emotionality (PE) was associated with enhanced RewP, lower age-9ADHD and lower age-12 inattention (IA). Negative emotionality (NE) was not associated with RewP or ADHD. Mediation analyses revealed the association between PE and hyperactivity/impulsivity (H/I) was mediated by RewP; enhanced RewP was associated with greater H/I. Greater PE was associated with enhanced RewP at a trend level. These effects held accounting for age-9 ADHD, age-12 IA and age-12 oppositional defiant and conduct disorder symptoms. https://www.selleckchem.com/products/fx11.html As such, preschool emotionality is associated with adolescent ADHD-H/I symptoms through late childhood initial responsiveness to reward. These relations indicate that individual differences in emotionality and reward responsiveness may be informative for personalizing ADHD interventions.Quantitative parameters for a two-state cooperative transition in duplex DNAs were finally obtained during the last 5 years. After a brief discussion of observations pertaining to the existence of the two-state equilibrium per se, the lengths, torsion, and bending elastic constants of the two states involved and the cooperativity parameter of the model are simply stated. Experimental tests of model predictions for the responses of DNA to small applied stretching, twisting, and bending stresses, and changes in temperature, ionic conditions, and sequence are described. The mechanism and significance of the large cooperativity, which enables significant DNA responses to such small perturbations, are also noted. The capacity of the model to resolve a number of long-standing and sometimes interconnected puzzles in the extant literature, including the origin of the broad pre-melting transition studied by numerous workers in the 1960s and 1970s, is demonstrated. Under certain conditions, the model predicts significant long-range attractive or repulsive interactions between hypothetical proteins with strong preferences for one or the other state that are bound to well-separated sites on the same DNA. A scenario is proposed for the activation of the ilvPG promoter on a supercoiled DNA by integration host factor.
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  • LED therapy could improve mini-implant stability after 2 months post-insertion. In conclusion, PBMT appears to be beneficial in ameliorating mini-implant stability. High energy density of LLLT might exert more rapid effect than low energy density. More high-quality clinical trials are needed to further demonstrate PBMT' effects on orthodontic mini-implants.Thiosemicarbazones (TSCs) encompasses a class of compounds relevant in the pharmacological context. Their specific applicability varies in function of the appropriated chemical modification and their binding to different transition metals. In the present work, we apply current standards functionals, B3LYP and B97D, with triple zeta basis set quality, 6-311++G(d,p), to investigate the relative stability of the various possible spatial arrangements for 2-acetylthiophene and 2-acetylthiophene-N1-phenyl thiosemicarbazones, denoted ATTSC and ATTSC-Ph, respectively. The relative stability of neutral and deprotonated species at ethanol described by an implicit solvent model was investigated. For ATTSC, the relative Gibbs energy changed significantly upon deprotonation, and for ATTSC-Ph, a novel global minimum was identified. Based on the present study, deprotonation determines population in condensed-media. Such information, valid for ATTSC and ATTSC-Ph, can be crucial in studying other thiosemicarbazones.Rice tungro disease (RTD) is a devastating disease of rice caused by combined infection with rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV), with one of the main symptoms being stunting. To dissect the molecular events responsible for RTD-induced stunting, the expression patterns of 23 cell-wall-related genes were examined in different rice lines with the same titers of RTSV but different titers of RTBV and in lines where only RTBV was present. Genes encoding cellulose synthases, expansins, glycosyl hydrolases, exostosins, and xyloglucan galactosyl transferase showed downregulation, whereas those encoding defensin or defensin-like proteins showed upregulation with increasing titers of RTBV. RTSV titers did not affect the expression levels of these genes. A similar relationship was seen for the reduction in the cellulose and pectin content and the accumulation of lignin. In silico analysis of promoters of the genes indicated a possible link to transcription factors reported earlier to respond to viral titers in rice. These results suggest a common network in which the genes related to the cell wall components are affected during infection with diverse viruses in rice.
    MET exon 14 skipping mutation, observed in 3-4% of non-small cell lung cancer (NSCLC), is emerging as a targetable alteration. In recent years, immune checkpoint inhibitors (ICI) have been effective in treating several NSCLCs. Our research aimed to investigate the characteristics of patients with NSCLCs harboring MET exon 14 mutations and their response to ICI in Japan.

    Among the 1954 consecutive NSCLCs diagnosed at Saitama Cancer Center between 2010 and 2019, MET exon 14 skipping mutations were detected in 68 (3.5%) NSCLCs. We evaluated their characteristics such as programmed cell death ligand 1 (PD-L1) expression.

    Median age of patients with NSCLCs harboring MET exon 14 skipping mutations was 73years. PD-L1 was highly expressed in 17 (70.8%) of the 24 patients examined. Seven patients received ICI monotherapy, and three out of seven had a remarkable treatment response, resulted in objective response rate (ORR) of 42.9% and progression-free survival of 24.7months. Three patients with donor splice-site mutations showed a long-term treatment response, despite the fact that two with acceptor splice-site mutations demonstrated no response and experienced early disease progression with ICI monotherapy.

    Our results indicated that patients with NSCLCs harboring MET exon 14 mutations presented with a high rate of positive PD-L1 expression. ICI treatment showed a high ORR and long-term efficacy for NSCLCs harboring MET exon 14 mutations. Variants of MET exon 14 splice-site mutations may be associated with ICI response.
    Our results indicated that patients with NSCLCs harboring MET exon 14 mutations presented with a high rate of positive PD-L1 expression. ICI treatment showed a high ORR and long-term efficacy for NSCLCs harboring MET exon 14 mutations. Variants of MET exon 14 splice-site mutations may be associated with ICI response.
    This study compared the quality of healthcare before and after implementation of a policy restructuring the healthcare delivery system and estimated the impact of centralization.

    We used the National Clinical Database to study patients undergoing esophagectomies from 2011 to 2016. We compared the effect of centralization based on the patient background, surgical mortality, and year of surgery. Difference-in-difference methods based on the generalized estimating equation logistic regression model were used for before-and-after comparisons after adjusting for patient-level expected surgical mortality.

    In total, 34,640 cases were identified. https://www.selleckchem.com/products/BI-2536.html More cases with risk factors were noted in ultra-low-volume hospitals, where 38.4% of cases in underpopulated areas were treated, than in higher volume facilities, and the operative mortality, readmission within 30days and length of stay were worse among patients treated in these hospitals. In centralized prefectures, the number of cases per hospital increased over time (7.2 in 2011 to 9.5 in 2016) while the crude operative mortality tended to decrease (3.4% in 2011 to 1.8% in 2016). The difference-in-difference estimator was 0.856 (95% confidence interval 0.639-1.147, p = 0.298).

    The centralization of ultra-low-volume hospitals did not lead to a deterioration in the quality of care but rather an improving trend.
    The centralization of ultra-low-volume hospitals did not lead to a deterioration in the quality of care but rather an improving trend.Juvenile xanthogranuloma (JXG) is a type of non-Langerhans cell histiocytosis that most commonly manifests as a solitary cutaneous lesion of the head and neck in children. Intracranial JXG is extremely rare. Although it is widely known that JXG skin lesions gradually disappear over time without treatment, treatment guidelines for intracranial JXG have not been established. It is very difficult to predict whether an intracranial lesion is JXG with only a pre-operative imaging work-up without pathologic confirmation. We report a case of the youngest, a 3-month-old male infant with an intracranial extra-axial mass with rapid growth for 2 months. Additionally, we suggest characteristic MRI findings for intracranial extra-axial JXG of a low T2 signal and a kidney bean shape.
    LED therapy could improve mini-implant stability after 2 months post-insertion. In conclusion, PBMT appears to be beneficial in ameliorating mini-implant stability. High energy density of LLLT might exert more rapid effect than low energy density. More high-quality clinical trials are needed to further demonstrate PBMT' effects on orthodontic mini-implants.Thiosemicarbazones (TSCs) encompasses a class of compounds relevant in the pharmacological context. Their specific applicability varies in function of the appropriated chemical modification and their binding to different transition metals. In the present work, we apply current standards functionals, B3LYP and B97D, with triple zeta basis set quality, 6-311++G(d,p), to investigate the relative stability of the various possible spatial arrangements for 2-acetylthiophene and 2-acetylthiophene-N1-phenyl thiosemicarbazones, denoted ATTSC and ATTSC-Ph, respectively. The relative stability of neutral and deprotonated species at ethanol described by an implicit solvent model was investigated. For ATTSC, the relative Gibbs energy changed significantly upon deprotonation, and for ATTSC-Ph, a novel global minimum was identified. Based on the present study, deprotonation determines population in condensed-media. Such information, valid for ATTSC and ATTSC-Ph, can be crucial in studying other thiosemicarbazones.Rice tungro disease (RTD) is a devastating disease of rice caused by combined infection with rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV), with one of the main symptoms being stunting. To dissect the molecular events responsible for RTD-induced stunting, the expression patterns of 23 cell-wall-related genes were examined in different rice lines with the same titers of RTSV but different titers of RTBV and in lines where only RTBV was present. Genes encoding cellulose synthases, expansins, glycosyl hydrolases, exostosins, and xyloglucan galactosyl transferase showed downregulation, whereas those encoding defensin or defensin-like proteins showed upregulation with increasing titers of RTBV. RTSV titers did not affect the expression levels of these genes. A similar relationship was seen for the reduction in the cellulose and pectin content and the accumulation of lignin. In silico analysis of promoters of the genes indicated a possible link to transcription factors reported earlier to respond to viral titers in rice. These results suggest a common network in which the genes related to the cell wall components are affected during infection with diverse viruses in rice. MET exon 14 skipping mutation, observed in 3-4% of non-small cell lung cancer (NSCLC), is emerging as a targetable alteration. In recent years, immune checkpoint inhibitors (ICI) have been effective in treating several NSCLCs. Our research aimed to investigate the characteristics of patients with NSCLCs harboring MET exon 14 mutations and their response to ICI in Japan. Among the 1954 consecutive NSCLCs diagnosed at Saitama Cancer Center between 2010 and 2019, MET exon 14 skipping mutations were detected in 68 (3.5%) NSCLCs. We evaluated their characteristics such as programmed cell death ligand 1 (PD-L1) expression. Median age of patients with NSCLCs harboring MET exon 14 skipping mutations was 73years. PD-L1 was highly expressed in 17 (70.8%) of the 24 patients examined. Seven patients received ICI monotherapy, and three out of seven had a remarkable treatment response, resulted in objective response rate (ORR) of 42.9% and progression-free survival of 24.7months. Three patients with donor splice-site mutations showed a long-term treatment response, despite the fact that two with acceptor splice-site mutations demonstrated no response and experienced early disease progression with ICI monotherapy. Our results indicated that patients with NSCLCs harboring MET exon 14 mutations presented with a high rate of positive PD-L1 expression. ICI treatment showed a high ORR and long-term efficacy for NSCLCs harboring MET exon 14 mutations. Variants of MET exon 14 splice-site mutations may be associated with ICI response. Our results indicated that patients with NSCLCs harboring MET exon 14 mutations presented with a high rate of positive PD-L1 expression. ICI treatment showed a high ORR and long-term efficacy for NSCLCs harboring MET exon 14 mutations. Variants of MET exon 14 splice-site mutations may be associated with ICI response. This study compared the quality of healthcare before and after implementation of a policy restructuring the healthcare delivery system and estimated the impact of centralization. We used the National Clinical Database to study patients undergoing esophagectomies from 2011 to 2016. We compared the effect of centralization based on the patient background, surgical mortality, and year of surgery. Difference-in-difference methods based on the generalized estimating equation logistic regression model were used for before-and-after comparisons after adjusting for patient-level expected surgical mortality. In total, 34,640 cases were identified. https://www.selleckchem.com/products/BI-2536.html More cases with risk factors were noted in ultra-low-volume hospitals, where 38.4% of cases in underpopulated areas were treated, than in higher volume facilities, and the operative mortality, readmission within 30days and length of stay were worse among patients treated in these hospitals. In centralized prefectures, the number of cases per hospital increased over time (7.2 in 2011 to 9.5 in 2016) while the crude operative mortality tended to decrease (3.4% in 2011 to 1.8% in 2016). The difference-in-difference estimator was 0.856 (95% confidence interval 0.639-1.147, p = 0.298). The centralization of ultra-low-volume hospitals did not lead to a deterioration in the quality of care but rather an improving trend. The centralization of ultra-low-volume hospitals did not lead to a deterioration in the quality of care but rather an improving trend.Juvenile xanthogranuloma (JXG) is a type of non-Langerhans cell histiocytosis that most commonly manifests as a solitary cutaneous lesion of the head and neck in children. Intracranial JXG is extremely rare. Although it is widely known that JXG skin lesions gradually disappear over time without treatment, treatment guidelines for intracranial JXG have not been established. It is very difficult to predict whether an intracranial lesion is JXG with only a pre-operative imaging work-up without pathologic confirmation. We report a case of the youngest, a 3-month-old male infant with an intracranial extra-axial mass with rapid growth for 2 months. Additionally, we suggest characteristic MRI findings for intracranial extra-axial JXG of a low T2 signal and a kidney bean shape.
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