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  • Excellent stability of P-60S-EDTA membrane in continuous operation of 36 h in both ideal and practical water environment suggests its promising application in real field heavy metal contaminated waste water treatment.The bystander effect is commonly defined as the observation of effects in nonirradiated cells and tissues when the later are in contact with irradiated cells/ tissues. More recently the occurrence of bystander effect between organisms of the same species has been also demonstrated. Nevertheless, there is limited knowledge about this effect between soil dwelling organisms from different taxonomic groups, as well as in response to stressors other than ionizing radiation. Moreover, data reporting this phenomenon for soil invertebrates are scarce. The results herein presented contribute for the understanding of the impacts of cadmium and uranium in the DNA integrity of two terrestrial oligochaetes species (Eisenia fetida and Enchytraeus albidus). The evaluation was based on the quantification of the effects in the DNA integrity of the coelomocytes using the alkaline comet assay technique. This work reports the existence of bystander signaling from terrestrial earthworms to enchytraeids and from enchytraeids to earthworms when the organisms were exposed to Cd. These results reinforce that the bystander effect seems to be related with the genotoxic activity of stressors, and not exclusive of radiotoxic contaminants. Further, the bystander effect occurs between different species and under real environmental conditions, even in complex matrices, as the soil.In this work, the cellulose-enriched mesocarp of tangerine peels (TP) and the lignin-enriched epicarp of the peels (e-TPs) were used as examples to unveil the link between the basic components (cellulose, hemicellulose and lignin) in lignocellulosic biomass and catalytic activity of biochar towards peroxymonosulfate (PMS) activation. The TP biochar exhibits sheet-like morphology and high porosity, while the e-TPs biochar shows a bulk morphology. Accordingly, the former outperformed the latter in terms of catalytic degradation of phenol with PMS, attributing to the higher content of cellulose than lignin in the TP precursor, which was further supported by comparing the catalytic activity of biochar prepared from binary mixtures containing different proportions of cellulose and lignin. Nonradical oxidation pathway based on singlet oxygen (1O2) and electron-transfer mechanism was involved in the TP biochar/PMS system and the key role of CO group in biochar for 1O2 generation was computationally demonstrated. Additionally, the unique porous structure and surface chemistry of TP biochar endows it an excellent adsorbent for various organic pollutants. Herein, this work provides an insight into the effect of lignocellulosic biomass source on the catalytic property of biochar, which would be beneficial to screen lignocellulosic biowastes to prepare high-performance biochar for water remediation.The compound 1,4-dioxane (DO) irritates the eyes, skin, and mucous membrane and is classified as a carcinogen. In this study, the decomposition of DO by photocatalytic reaction using liquid phase plasma (LPP) with photocatalyst was suggested. Plasma was directly discharged as an aqueous DO solution to enhance photocatalytic decomposition activity. To increase the decomposition efficiency of DO by plasma, bismuth ferrite (BFO) prepared by a sol-gel method was introduced as a visible-light photocatalyst. In the application of LPP and BFO photocatalyst, the decomposition of DO by photocatalytic reaction was evaluated. BFO showed UV-vis diffusion reflectance spectroscopy results of absorption of UV and visible light over 600 nm, with a bandgap of approximately 2.2 eV. BFO showed visible light photochemical reaction characteristics to decompose particulate matter (PM) in the irradiation of 6 W visible light LED lamps. It seems that the narrow bandgap of BFO led to the photocatalytic activity in the visible light. In the decomposition reaction of DO with a photocatalyst and LPP, BFO showed better decomposition efficiency than TiO2. BFO can cause photocatalytic reactions in both UV and visible light in the case of LPP irradiation, which emits strong ultraviolet and visible light.With the development of industry, the harm caused by volatile organic compound (VOC) gases to the human body has received **** attention. This study reveals as the first attempt to apply laser irradiation technique to the preparation of porous electrospun fibers with excellent low-concentration VOC gases adsorption properties. The laser-sensitive polycarbonate (PC) fibers prepared from electrospinning was treated in air by scanning with a neodymium-doped yttrium aluminum garnet (Nd YAG) pulsed laser beam to achieve porous structure. During the laser irradiation process, a series of changes such as melting, thermal degradation, and carbonization of the polymer fibers can change the surface structure. The morphology of the porous structure is related to the degree of laser-induced carbonization, and the laser current is an important parameter for determining the degree of laser-induced carbonization of a particular polymer. The results indicate that porous carbon structures can be created on the surface of the fiber membrane by controlling the degree of laser-induced carbonization, and a highly xylene gas adsorption efficiency is exhibited. This study may provide useful insights for developing electrospun porous fibers with VOC adsorption by simple, effective and environmentally friendly laser post-processing process.As more and more microplastics (MPs) and triclosan (TCS), which are added in consumer products, enter wastewater treatment plants with sewage, there are concerns about the impacts of the co-occurrence of MPs and TCS on biological wastewater treatment. In this study, the co-effects of four 1 mg/L MPs (polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC) and polyamide (PA)) and 0.5 mg/L TCS on nitrification were investigated in lab-scale nitrifying sequencing batch reactors (SBRs) (SBR-PE, SBR-PS, SBR-PVC and SBR-PA) relative to control which received no MPs (SBR-CK). The removal rates of NH4+-N and TCS in SBR-CK were around 100% and 92%, respectively. Compared with SBR-CK, no measurable inhibition was observed on nitrification in SBR-PE and SBR-PS, however, SBR-PVC and SBR-PA rapidly lost nitrification function during 14 days, which might be due to the reducing of MLSS caused by PVC, PA and TCS co-loading. https://www.selleckchem.com/products/d609.html Furthermore, PS, PVC and PA decreased the removal of TCS. The co-occurrence of TCS and PS, PVC, PA increased extracellular polymeric substances, reduced microbial diversity and shifted microbial communities.
    Excellent stability of P-60S-EDTA membrane in continuous operation of 36 h in both ideal and practical water environment suggests its promising application in real field heavy metal contaminated waste water treatment.The bystander effect is commonly defined as the observation of effects in nonirradiated cells and tissues when the later are in contact with irradiated cells/ tissues. More recently the occurrence of bystander effect between organisms of the same species has been also demonstrated. Nevertheless, there is limited knowledge about this effect between soil dwelling organisms from different taxonomic groups, as well as in response to stressors other than ionizing radiation. Moreover, data reporting this phenomenon for soil invertebrates are scarce. The results herein presented contribute for the understanding of the impacts of cadmium and uranium in the DNA integrity of two terrestrial oligochaetes species (Eisenia fetida and Enchytraeus albidus). The evaluation was based on the quantification of the effects in the DNA integrity of the coelomocytes using the alkaline comet assay technique. This work reports the existence of bystander signaling from terrestrial earthworms to enchytraeids and from enchytraeids to earthworms when the organisms were exposed to Cd. These results reinforce that the bystander effect seems to be related with the genotoxic activity of stressors, and not exclusive of radiotoxic contaminants. Further, the bystander effect occurs between different species and under real environmental conditions, even in complex matrices, as the soil.In this work, the cellulose-enriched mesocarp of tangerine peels (TP) and the lignin-enriched epicarp of the peels (e-TPs) were used as examples to unveil the link between the basic components (cellulose, hemicellulose and lignin) in lignocellulosic biomass and catalytic activity of biochar towards peroxymonosulfate (PMS) activation. The TP biochar exhibits sheet-like morphology and high porosity, while the e-TPs biochar shows a bulk morphology. Accordingly, the former outperformed the latter in terms of catalytic degradation of phenol with PMS, attributing to the higher content of cellulose than lignin in the TP precursor, which was further supported by comparing the catalytic activity of biochar prepared from binary mixtures containing different proportions of cellulose and lignin. Nonradical oxidation pathway based on singlet oxygen (1O2) and electron-transfer mechanism was involved in the TP biochar/PMS system and the key role of CO group in biochar for 1O2 generation was computationally demonstrated. Additionally, the unique porous structure and surface chemistry of TP biochar endows it an excellent adsorbent for various organic pollutants. Herein, this work provides an insight into the effect of lignocellulosic biomass source on the catalytic property of biochar, which would be beneficial to screen lignocellulosic biowastes to prepare high-performance biochar for water remediation.The compound 1,4-dioxane (DO) irritates the eyes, skin, and mucous membrane and is classified as a carcinogen. In this study, the decomposition of DO by photocatalytic reaction using liquid phase plasma (LPP) with photocatalyst was suggested. Plasma was directly discharged as an aqueous DO solution to enhance photocatalytic decomposition activity. To increase the decomposition efficiency of DO by plasma, bismuth ferrite (BFO) prepared by a sol-gel method was introduced as a visible-light photocatalyst. In the application of LPP and BFO photocatalyst, the decomposition of DO by photocatalytic reaction was evaluated. BFO showed UV-vis diffusion reflectance spectroscopy results of absorption of UV and visible light over 600 nm, with a bandgap of approximately 2.2 eV. BFO showed visible light photochemical reaction characteristics to decompose particulate matter (PM) in the irradiation of 6 W visible light LED lamps. It seems that the narrow bandgap of BFO led to the photocatalytic activity in the visible light. In the decomposition reaction of DO with a photocatalyst and LPP, BFO showed better decomposition efficiency than TiO2. BFO can cause photocatalytic reactions in both UV and visible light in the case of LPP irradiation, which emits strong ultraviolet and visible light.With the development of industry, the harm caused by volatile organic compound (VOC) gases to the human body has received much attention. This study reveals as the first attempt to apply laser irradiation technique to the preparation of porous electrospun fibers with excellent low-concentration VOC gases adsorption properties. The laser-sensitive polycarbonate (PC) fibers prepared from electrospinning was treated in air by scanning with a neodymium-doped yttrium aluminum garnet (Nd YAG) pulsed laser beam to achieve porous structure. During the laser irradiation process, a series of changes such as melting, thermal degradation, and carbonization of the polymer fibers can change the surface structure. The morphology of the porous structure is related to the degree of laser-induced carbonization, and the laser current is an important parameter for determining the degree of laser-induced carbonization of a particular polymer. The results indicate that porous carbon structures can be created on the surface of the fiber membrane by controlling the degree of laser-induced carbonization, and a highly xylene gas adsorption efficiency is exhibited. This study may provide useful insights for developing electrospun porous fibers with VOC adsorption by simple, effective and environmentally friendly laser post-processing process.As more and more microplastics (MPs) and triclosan (TCS), which are added in consumer products, enter wastewater treatment plants with sewage, there are concerns about the impacts of the co-occurrence of MPs and TCS on biological wastewater treatment. In this study, the co-effects of four 1 mg/L MPs (polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC) and polyamide (PA)) and 0.5 mg/L TCS on nitrification were investigated in lab-scale nitrifying sequencing batch reactors (SBRs) (SBR-PE, SBR-PS, SBR-PVC and SBR-PA) relative to control which received no MPs (SBR-CK). The removal rates of NH4+-N and TCS in SBR-CK were around 100% and 92%, respectively. Compared with SBR-CK, no measurable inhibition was observed on nitrification in SBR-PE and SBR-PS, however, SBR-PVC and SBR-PA rapidly lost nitrification function during 14 days, which might be due to the reducing of MLSS caused by PVC, PA and TCS co-loading. https://www.selleckchem.com/products/d609.html Furthermore, PS, PVC and PA decreased the removal of TCS. The co-occurrence of TCS and PS, PVC, PA increased extracellular polymeric substances, reduced microbial diversity and shifted microbial communities.
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  • Microalgae have been recently cultivated using resources from wastewater treatment plants, including nutrients, CO2, and heat. In the present study, we focused on the natural cultivation of total microalgae rather than specific microalgae, for which culture conditions and the cultivation environment are difficult to prepare. Natural microalgal cultivation systems using 380-L raceway tanks were operated outdoors for 8 months and the effects of the culture substrate were investigated. The cultivation substrate was the primary effluent with or without excess sludge. The results showed that when diluted excess sludge was added to the substrate, microalgal biomass increased more than when the substrate contained only primary effluent. Additionally, the wastewater suspended matter and water quality were removed, reaching low levels. Microalgal culture systems using excess sludge showed higher organic acid content, higher biochemical methane potential, and higher efficiency in producing more microalgal biomass than wastewater treatment plant systems that did not use excess sludge.in English, German Zusammenfassung. Hintergrund und Ziel Um den Bedürfnissen und Bedarfen von Personen mit Demenz, ihren Angehörigen und ihren Betreuungspersonen in den jeweiligen komplexen Lebens- und Pflegesituationen gerecht zu werden, bedarf es einer inhaltlichen Auseinandersetzung mit Forschungsschwerpunkten. Das Ziel dieser Arbeit war die Identifikation und Priorisierung von Pflegeforschungsschwerpunkten für das Themenfeld „Dementia Care“ im deutschsprachigen Raum. Methoden Es erfolgte eine systematische Literaturrecherche nach bestehenden Forschungsagenden zum Themenfeld „Dementia Care“. Im Rahmen eines Delphi-Verfahrens ergänzten systematisch identifizierte Demenzpflegeexpertinnen und -experten aus dem deutschsprachigen Raum die extrahierten Forschungsschwerpunkte und schätzten deren Wichtigkeit ein. Anschließend priorisierten die Teilnehmenden die als wichtig erachteten Forschungsschwerpunkte. https://www.selleckchem.com/products/ag-825.html Ergebnisse Fünfzehn Expertinnen und Experten ergänzten 61 identifizierte Forschungsthemen, die in bereits bestehenden Forschungsagenden enthalten sind. Insgesamt schätzten sie 107 Themen hinsichtlich ihrer Wichtigkeit ein. Sie priorisierten 79 mehrheitlich als wichtig erachtete Themen. Schlussfolgerungen Die erarbeiteten Forschungsprioritäten sind ein möglicher Orientierungsrahmen für die Pflegewissenschaft, die Gesundheitspolitik und die Forschungsförderung, um Forschungsaktivitäten strukturiert nachgehen zu können. Es ist empfehlenswert, die Prioritäten in regelmäßigen Abständen zu ergänzen und erneut zur Diskussion zu stellen, damit Aktualität gewährleistet ist.Despite a connection between road traffic and air pollution has been clearly identified, few integrated analyses on air quality and mobility policies are currently available worldwide. Aim of this work is to build a framework for the evaluation of the impact of mobility policies on air quality in 14 major Italian cities, on a long-time scale (2006-2016). Air quality data was collected from all PM10, PM2.5, and NO2 monitoring stations, installed in compliance with the European directive 2008/50/EC. A large dataset was collected, including public transport, environmental, and fuel categorization of the private vehicular fleet, low emissions zones and modal split. In the analyzed time period, both public transportation use and private motorization decreased. Considering the environmental classification standards of vehicles, Northern cities are more readily switching to newer and less polluting cars (e.g. Euro 5 and Euro 6). There has been a general reduction in PM and NO2 concentration. Nevertheless, exceedances are still above the targeted limit value, mainly in some Northern cities who made major investments in sustainable and shared mobility this highlights a strong influence of climatic conditions and other sources. Dramatic variations in the CO/NO ratio were observed in Turin, while smaller changes are observed in Milan, Rome and Palermo.Effectiveness of a 12-week cognitive training (CT) programme for community-dwelling patients with dementia was evaluated on various cognitive functions (attention, memory, executive functions and reasoning) and psychological well-being (PWB). A single-blind randomized controlled trial was conducted in adult day care centres in Helsinki, Finland. Participants (N = 147) were older individuals with mild to moderate dementia living at home and attending day care (mean age 83 years, 72% female, 63% at mild stage of dementia). The intervention group (n = 76) received systematic CT for 45 min twice a week while the control group (n = 71) attended day care as usual. The cognitive and psychological outcomes were measured at baseline, and followed up at 3 and 9 months. No differences between the two groups in changes of any of the cognitive functions, or PWB over time were found. We observed a positive trend at 3 months in the change for PWB favouring the intervention group, but no significant interaction effect was found (p = .079; d = -0.31). Thus, systematic CT appears to have no effect on neuropsychological outcomes of cognitive functioning and PWB in older adults who already have dementia.Intrinsically disordered proteins are now widely accepted to play crucial roles in biological functions. Identification of signatures of intrinsic disorder is one of the key steps towards building a proper repertoire for their occurrence in proteomes. In this work, systematic computational synthesis of a library of all possible (3368400) dipeptides, tripeptides, tetrapeptides and pentapeptides using the natural 20 amino acids allowed us to identify 36 unique tetrapeptides present exclusively in intrinsically disordered proteins and absent in the complete primary sequence space of naturally occurring structured proteins. Further, out of more than 530000 known naturally occurring primary sequences without any structural information, 1349 sequences contain the above identified unique signatures of intrinsic disorder. These sequences, having cellular functions varying from housekeeping to metabolic to transport, more than double the number of the currently known intrinsically disordered proteins. On similar lines, we report that 26577 pentapeptide signatures exclusive to intrinsically disordered proteins, and absent in naturally occurring structured proteins, identify ∼50% of more than half-a-million curated protein sequences without structural information to be intrinsically disordered.
    Microalgae have been recently cultivated using resources from wastewater treatment plants, including nutrients, CO2, and heat. In the present study, we focused on the natural cultivation of total microalgae rather than specific microalgae, for which culture conditions and the cultivation environment are difficult to prepare. Natural microalgal cultivation systems using 380-L raceway tanks were operated outdoors for 8 months and the effects of the culture substrate were investigated. The cultivation substrate was the primary effluent with or without excess sludge. The results showed that when diluted excess sludge was added to the substrate, microalgal biomass increased more than when the substrate contained only primary effluent. Additionally, the wastewater suspended matter and water quality were removed, reaching low levels. Microalgal culture systems using excess sludge showed higher organic acid content, higher biochemical methane potential, and higher efficiency in producing more microalgal biomass than wastewater treatment plant systems that did not use excess sludge.in English, German Zusammenfassung. Hintergrund und Ziel Um den Bedürfnissen und Bedarfen von Personen mit Demenz, ihren Angehörigen und ihren Betreuungspersonen in den jeweiligen komplexen Lebens- und Pflegesituationen gerecht zu werden, bedarf es einer inhaltlichen Auseinandersetzung mit Forschungsschwerpunkten. Das Ziel dieser Arbeit war die Identifikation und Priorisierung von Pflegeforschungsschwerpunkten für das Themenfeld „Dementia Care“ im deutschsprachigen Raum. Methoden Es erfolgte eine systematische Literaturrecherche nach bestehenden Forschungsagenden zum Themenfeld „Dementia Care“. Im Rahmen eines Delphi-Verfahrens ergänzten systematisch identifizierte Demenzpflegeexpertinnen und -experten aus dem deutschsprachigen Raum die extrahierten Forschungsschwerpunkte und schätzten deren Wichtigkeit ein. Anschließend priorisierten die Teilnehmenden die als wichtig erachteten Forschungsschwerpunkte. https://www.selleckchem.com/products/ag-825.html Ergebnisse Fünfzehn Expertinnen und Experten ergänzten 61 identifizierte Forschungsthemen, die in bereits bestehenden Forschungsagenden enthalten sind. Insgesamt schätzten sie 107 Themen hinsichtlich ihrer Wichtigkeit ein. Sie priorisierten 79 mehrheitlich als wichtig erachtete Themen. Schlussfolgerungen Die erarbeiteten Forschungsprioritäten sind ein möglicher Orientierungsrahmen für die Pflegewissenschaft, die Gesundheitspolitik und die Forschungsförderung, um Forschungsaktivitäten strukturiert nachgehen zu können. Es ist empfehlenswert, die Prioritäten in regelmäßigen Abständen zu ergänzen und erneut zur Diskussion zu stellen, damit Aktualität gewährleistet ist.Despite a connection between road traffic and air pollution has been clearly identified, few integrated analyses on air quality and mobility policies are currently available worldwide. Aim of this work is to build a framework for the evaluation of the impact of mobility policies on air quality in 14 major Italian cities, on a long-time scale (2006-2016). Air quality data was collected from all PM10, PM2.5, and NO2 monitoring stations, installed in compliance with the European directive 2008/50/EC. A large dataset was collected, including public transport, environmental, and fuel categorization of the private vehicular fleet, low emissions zones and modal split. In the analyzed time period, both public transportation use and private motorization decreased. Considering the environmental classification standards of vehicles, Northern cities are more readily switching to newer and less polluting cars (e.g. Euro 5 and Euro 6). There has been a general reduction in PM and NO2 concentration. Nevertheless, exceedances are still above the targeted limit value, mainly in some Northern cities who made major investments in sustainable and shared mobility this highlights a strong influence of climatic conditions and other sources. Dramatic variations in the CO/NO ratio were observed in Turin, while smaller changes are observed in Milan, Rome and Palermo.Effectiveness of a 12-week cognitive training (CT) programme for community-dwelling patients with dementia was evaluated on various cognitive functions (attention, memory, executive functions and reasoning) and psychological well-being (PWB). A single-blind randomized controlled trial was conducted in adult day care centres in Helsinki, Finland. Participants (N = 147) were older individuals with mild to moderate dementia living at home and attending day care (mean age 83 years, 72% female, 63% at mild stage of dementia). The intervention group (n = 76) received systematic CT for 45 min twice a week while the control group (n = 71) attended day care as usual. The cognitive and psychological outcomes were measured at baseline, and followed up at 3 and 9 months. No differences between the two groups in changes of any of the cognitive functions, or PWB over time were found. We observed a positive trend at 3 months in the change for PWB favouring the intervention group, but no significant interaction effect was found (p = .079; d = -0.31). Thus, systematic CT appears to have no effect on neuropsychological outcomes of cognitive functioning and PWB in older adults who already have dementia.Intrinsically disordered proteins are now widely accepted to play crucial roles in biological functions. Identification of signatures of intrinsic disorder is one of the key steps towards building a proper repertoire for their occurrence in proteomes. In this work, systematic computational synthesis of a library of all possible (3368400) dipeptides, tripeptides, tetrapeptides and pentapeptides using the natural 20 amino acids allowed us to identify 36 unique tetrapeptides present exclusively in intrinsically disordered proteins and absent in the complete primary sequence space of naturally occurring structured proteins. Further, out of more than 530000 known naturally occurring primary sequences without any structural information, 1349 sequences contain the above identified unique signatures of intrinsic disorder. These sequences, having cellular functions varying from housekeeping to metabolic to transport, more than double the number of the currently known intrinsically disordered proteins. On similar lines, we report that 26577 pentapeptide signatures exclusive to intrinsically disordered proteins, and absent in naturally occurring structured proteins, identify ∼50% of more than half-a-million curated protein sequences without structural information to be intrinsically disordered.
    0 Yorumlar 0 hisse senetleri 34 Views 0 önizleme

  • No effective treatment for COVID-19 has been well established yet. Nafamostat, known as anticoagulant, has potential anti-inflammatory and anti-viral activities against COVID-19. We report three cases of COVID-19 pneumonia who progressed while using antiviral drugs and needed supplementary oxygen therapy, improved after treatment with nafamostat. These preliminary findings show the possibility that Nafamostat can be considered to be used in elderly patients with COVID-19 pneumonia who need oxygen therapy. The effectiveness of nafamostat should be evaluated in further studies.COVID-19 associated cytokine storm could induce ARDS rapidly and the patients would require the support of mechanic ventilation. However, the prognosis was not that optimistic. The outcome might be changed if the intervention of EBP was performed timely. We present a case of severe SARS-CoV-2 infection who recovered from cytokine storm.Endocarditis due to Lactobacillus species is extremely rare. We report an uncommon case of Lactobacillus plantarum bioprosthetic aortic valve endocarditis, presenting with severe aortic steno-regurgitation, which responded to conventional medical and surgical treatment. This case provides a better understanding of the disease process of L. plantarum and highlights the role of transesophageal echocardiography in following the entire course of endocarditis.Pneumonia can be stopped while fight against the SARS-COV-2 outbreak.•Pneumonia cases (except COVID-19 cases) were dramatically decreased since the control measures were onset.•Other respiratory infection diseases may also to some extent be stopped while fighting against the pandemic of COVID-19.Inorganic dietary nitrate plays vital roles in biological functions via the exogenous NO3-/NO2-/NO pathway under hypoxia and ischemia. We previously verified the antioxidative effects of inorganic nitrate in a mouse model of total body irradiation (TBI). Accordingly, in this study, we evaluated the effects of inorganic nitrate on prevention of TBI-induced colon injury and dysbiosis of the gut microbiome. Nitrate significantly rescued the abnormal biological indexes (body weight, white blood cell, red blood cell, platelet, hemoglobin level and intestinal canal lengths) induced by TBI. Then, we detected oxidative stress and DNA damage indexes (phospho-histone H2AX and p53 binding protein 1), which were both increased by irradiation (IR) and alleviated by nitrate. IR-induced apoptosis and senescence were ameliorated by inorganic nitrate. The distribution of the gut microbiome differed for **** with TBI and those receiving inorganic nitrate. The average abundance of Lactobacillus significantly increased, and that of Bacteroidales decreased at the genus level in the nitrate group compared with that in the IR alone group. At 30 days after TBI, the abundances of Bacteroides and Faecalibaculum decreased, whereas that of Lactobacillus increased in the IR + nitrate group compared with that in the IR alone group. Inorganic nitrate efficiently prevents TBI-induced colon epithelium injury and maintains the homeostasis of the gut microbiome. Thus, our results showed that inorganic nitrate might be a promising treatment for TBI induced colon injury.Objective This study investigated whether melatonin alleviates intervertebral disc degeneration (IVDD) by promoting autophagy through inhibiting the NF-κB signaling pathway. Methods Magnetic resonance imaging (MRI), hematoxylin and eosin (H&E) staining and Safranin-O staining were used to measure disc degeneration in rat needle puncture IVDD models, and melatonin was injected intraperitoneally in the treated group to test its function. The expression of autophagy and extracellular matrix (ECM) degeneration related-markers were measured in the discs using immunohistochemistry. Transmission electron microscopy was used to evaluate the activation of autophagy in human nucleus pulposus (NP) tissues with different degenerated statuses. The expression of autophagy and disc degeneration related-markers were detected in NP cells by Western blot, RT-qPCR, and immunofluorescence analyses. https://www.selleckchem.com/products/triparanol-mer-29.html NF-κB signaling pathway involvement was studied by lentivirus-mediated knockdown, Western blotting, and immunohistochemistry and immunofluorescence staining. Results Melatonin prevented IVDD development in vivo and in vitro. Compared to non-degenerated disc tissues, degenerated human NP tissues showed a decrease in the autophagy-specific marker LC3B and the numbers of autophagosomes and autolysosomes, whereas the p62 level was increased; similar results were observed in rat IVDD models, indicating a negative correlation between autophagy and IVDD. Furthermore, both in vivo and in vitro studies found that melatonin application induced autophagy and reduced ECM disc degradation. Melatonin was also shown to regulate autophagy by inhibiting the NF-κB signaling pathway in vivo and vitro. Conclusion This study indicates that melatonin prevents IVDD by promoting autophagy, indicating its possible therapeutic potential for controlling the progression of IVDD.Objectives Subchondral bone may contribute to knee osteoarthritis (OA) pain. Nerve growth factor (NGF) can stimulate nerve growth through TrkA. We aimed to identify how sensory nerve growth at the osteochondral junction in human and rat knees associates with OA pain. Methods Eleven symptomatic chondropathy cases were selected from people undergoing total knee replacement for OA. Twelve asymptomatic chondropathy cases who had not presented with knee pain were selected post-mortem. OA was induced in rat knees by meniscal transection (MNX) and sham-operated rats were used as controls. Twice-daily oral doses (30 mg/kg) of TrkA inhibitor (AR786) or vehicle were administered from before and up to 28 days after OA induction. Joints were analysed for macroscopic appearances of articular surfaces, OA histopathology and calcitonin gene-related peptide-immunoreactive (CGRP-IR) sensory nerves in medial tibial plateaux, and rats were assessed for pain behaviors. Results The percentage of osteochondral channels containing CGRP-IR nerves in symptomatic chondropathy was higher than in asymptomatic chondropathy (difference 2.5% [95% CI 1.1-3.7]), and in MNX-than in sham-operated rat knees (difference 7.8% [95%CI 1.7-15.0]). Osteochondral CGRP-IR innervation was significantly associated with pain behavior in rats. Treatment with AR786 prevented the increase in CGRP-IR nerves in osteochondral channels and reduced pain behavior in MNX-operated rats. Structural OA was not significantly affected by AR786 treatment. Conclusions CGRP-IR sensory nerves within osteochondral channels are associated with pain in human and rat knee OA. Reduced pathological innervation of the osteochondral junction might contribute to analgesic effects of reduced NGF activity achieved by blocking TrkA.
    No effective treatment for COVID-19 has been well established yet. Nafamostat, known as anticoagulant, has potential anti-inflammatory and anti-viral activities against COVID-19. We report three cases of COVID-19 pneumonia who progressed while using antiviral drugs and needed supplementary oxygen therapy, improved after treatment with nafamostat. These preliminary findings show the possibility that Nafamostat can be considered to be used in elderly patients with COVID-19 pneumonia who need oxygen therapy. The effectiveness of nafamostat should be evaluated in further studies.COVID-19 associated cytokine storm could induce ARDS rapidly and the patients would require the support of mechanic ventilation. However, the prognosis was not that optimistic. The outcome might be changed if the intervention of EBP was performed timely. We present a case of severe SARS-CoV-2 infection who recovered from cytokine storm.Endocarditis due to Lactobacillus species is extremely rare. We report an uncommon case of Lactobacillus plantarum bioprosthetic aortic valve endocarditis, presenting with severe aortic steno-regurgitation, which responded to conventional medical and surgical treatment. This case provides a better understanding of the disease process of L. plantarum and highlights the role of transesophageal echocardiography in following the entire course of endocarditis.Pneumonia can be stopped while fight against the SARS-COV-2 outbreak.•Pneumonia cases (except COVID-19 cases) were dramatically decreased since the control measures were onset.•Other respiratory infection diseases may also to some extent be stopped while fighting against the pandemic of COVID-19.Inorganic dietary nitrate plays vital roles in biological functions via the exogenous NO3-/NO2-/NO pathway under hypoxia and ischemia. We previously verified the antioxidative effects of inorganic nitrate in a mouse model of total body irradiation (TBI). Accordingly, in this study, we evaluated the effects of inorganic nitrate on prevention of TBI-induced colon injury and dysbiosis of the gut microbiome. Nitrate significantly rescued the abnormal biological indexes (body weight, white blood cell, red blood cell, platelet, hemoglobin level and intestinal canal lengths) induced by TBI. Then, we detected oxidative stress and DNA damage indexes (phospho-histone H2AX and p53 binding protein 1), which were both increased by irradiation (IR) and alleviated by nitrate. IR-induced apoptosis and senescence were ameliorated by inorganic nitrate. The distribution of the gut microbiome differed for mice with TBI and those receiving inorganic nitrate. The average abundance of Lactobacillus significantly increased, and that of Bacteroidales decreased at the genus level in the nitrate group compared with that in the IR alone group. At 30 days after TBI, the abundances of Bacteroides and Faecalibaculum decreased, whereas that of Lactobacillus increased in the IR + nitrate group compared with that in the IR alone group. Inorganic nitrate efficiently prevents TBI-induced colon epithelium injury and maintains the homeostasis of the gut microbiome. Thus, our results showed that inorganic nitrate might be a promising treatment for TBI induced colon injury.Objective This study investigated whether melatonin alleviates intervertebral disc degeneration (IVDD) by promoting autophagy through inhibiting the NF-κB signaling pathway. Methods Magnetic resonance imaging (MRI), hematoxylin and eosin (H&E) staining and Safranin-O staining were used to measure disc degeneration in rat needle puncture IVDD models, and melatonin was injected intraperitoneally in the treated group to test its function. The expression of autophagy and extracellular matrix (ECM) degeneration related-markers were measured in the discs using immunohistochemistry. Transmission electron microscopy was used to evaluate the activation of autophagy in human nucleus pulposus (NP) tissues with different degenerated statuses. The expression of autophagy and disc degeneration related-markers were detected in NP cells by Western blot, RT-qPCR, and immunofluorescence analyses. https://www.selleckchem.com/products/triparanol-mer-29.html NF-κB signaling pathway involvement was studied by lentivirus-mediated knockdown, Western blotting, and immunohistochemistry and immunofluorescence staining. Results Melatonin prevented IVDD development in vivo and in vitro. Compared to non-degenerated disc tissues, degenerated human NP tissues showed a decrease in the autophagy-specific marker LC3B and the numbers of autophagosomes and autolysosomes, whereas the p62 level was increased; similar results were observed in rat IVDD models, indicating a negative correlation between autophagy and IVDD. Furthermore, both in vivo and in vitro studies found that melatonin application induced autophagy and reduced ECM disc degradation. Melatonin was also shown to regulate autophagy by inhibiting the NF-κB signaling pathway in vivo and vitro. Conclusion This study indicates that melatonin prevents IVDD by promoting autophagy, indicating its possible therapeutic potential for controlling the progression of IVDD.Objectives Subchondral bone may contribute to knee osteoarthritis (OA) pain. Nerve growth factor (NGF) can stimulate nerve growth through TrkA. We aimed to identify how sensory nerve growth at the osteochondral junction in human and rat knees associates with OA pain. Methods Eleven symptomatic chondropathy cases were selected from people undergoing total knee replacement for OA. Twelve asymptomatic chondropathy cases who had not presented with knee pain were selected post-mortem. OA was induced in rat knees by meniscal transection (MNX) and sham-operated rats were used as controls. Twice-daily oral doses (30 mg/kg) of TrkA inhibitor (AR786) or vehicle were administered from before and up to 28 days after OA induction. Joints were analysed for macroscopic appearances of articular surfaces, OA histopathology and calcitonin gene-related peptide-immunoreactive (CGRP-IR) sensory nerves in medial tibial plateaux, and rats were assessed for pain behaviors. Results The percentage of osteochondral channels containing CGRP-IR nerves in symptomatic chondropathy was higher than in asymptomatic chondropathy (difference 2.5% [95% CI 1.1-3.7]), and in MNX-than in sham-operated rat knees (difference 7.8% [95%CI 1.7-15.0]). Osteochondral CGRP-IR innervation was significantly associated with pain behavior in rats. Treatment with AR786 prevented the increase in CGRP-IR nerves in osteochondral channels and reduced pain behavior in MNX-operated rats. Structural OA was not significantly affected by AR786 treatment. Conclusions CGRP-IR sensory nerves within osteochondral channels are associated with pain in human and rat knee OA. Reduced pathological innervation of the osteochondral junction might contribute to analgesic effects of reduced NGF activity achieved by blocking TrkA.
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  • Plasma phosphorylated survivin levels in having BD patients were also downregulated compared to healthy individuals. Conclusion Analysis of PBMCs indicated increasing expression level of phosphorylated survivin in PBMCs of BD patients. There was also a downregulation in phosphorylated survivin levels in plasma of BD patients. © 2020 The Authors.Purpose Despite the discovery and synthesis of several anticancer drugs, cancer is still a major life threatening incident for human beings after cardiovascular diseases. Toxicity, severe side effects, and drug resistance are serious problems of available commercial anticancer drugs. Coumarins are synthetic and natural heterocycles that show promising antiproliferative activities against various tumors. The aim of this research is to computationally study the coumarin derivatives in order to develop reliable quantitative structure-activity relationship (QSAR) models for predicting their anticancer activities. Methods A data set of thirty one coumarin analogs with significant antiproliferative activities toward HepG2 cells were selected from the literature. The molecular descriptors for these compounds were calculated using Dragon, HyperChem, and ACD/Labs programs. Genetic algorithm (GA) accompanied by multiple linear regression (MLR) for simultaneous feature selection and model development was employed for generating the QSAR models. Results Based on the obtained results, the developed linear QSAR models with three and four descriptors showed good predictive power with r2 values of 0.670 and 0.692, respectively. Moreover, the calculated validation parameters for the models confirmed the reliability of the QSAR models. Conclusion The findings of the current study could be useful for the design and synthesis of novel anticancer drugs based on coumarin structure. © 2020 The Authors.Purpose Helicobacter pylori is recognized as one of the prevalent causes of human gastricinfection. In the present study, the role of mixed immunization with H. pylori lipopolysaccharide(LPS) and recombinant cytotoxin-associated gene A (rCagA) as a stimulator of host immuneresponses was determined. https://www.selleckchem.com/products/d609.html Methods BALB/c **** were immunized with different formulations by the systemic administrationat 14-day intervals. The effects of the formulations plus CpG adjuvants were assessed before andpost-immunization in separated studies. Moreover, the expression of Th1/Th2 cytokines wasquantified in sera of immunized **** using reverse transcription polymerase chain reaction (RTPCR)test and the protein levels confirmed with enzyme linked immunosorbent assay (ELISA).Finally, the specific antibody levels in sera were studied by ELISA and the tendency of cellularresponse was examined by IgG1/IgG2a ratio. Results Data of Western blotting verified the presence of constructed protein. Analysisof lymphocyte proliferation showed that CpG-conjugated rCagA increases lymphocytesproliferation compared to the control group. Also, it was shown that formulations containing LPSand rCagA promote a Th1 response indicated by interferon-gamma expression and induced Th1/Th2 balance. Additionally, the specific IgG1, total IgG and IgG2a levels elevated in response toall treatments. Ultimately, the IgG2a/IgG1 ratio in the **** immunized with rCagA-containingformulations increased. Conclusion These results indicated that rCagA protein carried with CpG adjuvant not onlymaintained its antigenicity throughout the experiment but also induced robust Th1-biasedimmune responses. Therefore, it holds promise for the production of an efficient vaccine against H. pylori infection. © 2020 The Authors.Purpose Due to the potential industrial and therapeutic applications of the yeast exopolysaccharides (EPSs), there has been an increasing demand to assess these biopolymers with improved characteristics. This study aimed to characterize the EPSs from Rhodosporidium babjevae (ATCC 90942 and IBRC-M 30088) as well as to evaluate their possible antioxidant, emulsifying and antiproliferative activities. Methods Rhodosporidium babjevae was cultured for 5 days and following isolation of supernatant, EPSs precipitated with adding of cold absolute ethanol and freeze-dried. The EPSs chemical structure was determined by FT-IR, SEM, HPLC-SEC and GC-MS. Additionally the solubility, water holding capacity and emulsifying activity of EPSs were evaluated. In vitro, antioxidant activity was investigated against DPPH, superoxide and hydroxyl radicals. Finally the EPSs consequence on the cell proliferation of human breast adenocarcinoma (MCF-7) and Madin-Darby canine kidney (****) cell lines was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Results R. babjevae excreted 1.6±0.2 g/L of the EPSs. The EPSs had three fractions with molecular weights of 1.02 ×106 , 5×105 and 2×105 Da. Mannose and glucose were found as the main monosaccharides of the EPSs (8416 mol%, respectively). The EPSs exhibited emulsifying activity on sun flower oil. The scavenging activities were found to be dose-dependent and higher than hyaluronic acid. Significant difference among the EPSs treatments on the proliferation of MCF-7 and **** cell lines was not observed (P>0.05). Conclusion These results show the interesting potential of the EPSs from R. babjevae as biocompatible compounds for using in food and pharmaceutical fields. © 2020 The Authors.Purpose Estriol (ERL) is a type of hormone among the groups of estrogen hormone that was detected through the voltammetric technique by constructing an electrochemical sensor based on the octoxynol-9 modified graphite paste electrode (OXL-9MGPE). Methods Using the strategy of cyclic voltammetry (CV) and differential pulse voltammetry (DPV) with a bare graphite paste electrode (BGPE) immobilized with OXL-9, ERL electro-oxidation has been assessed in 0.2 M phosphate buffer solution (PBS) of pH 6.0. The fabricated electrode has substantial electrochemical sensing efficiency, and the ERL oxidation at the OXL-9MGPE was the irreversible process. The surface morphological characteristics of BGPE and OXL-9MGPE were differentiated with the help of field emission scanning electron microscopy (FE-SEM). Results The impact of various factors such as scan rate, pH, reproducibility, repeatability, and stability on the electro-oxidation of ERL was evaluated. Techniques of CV and DPV were utilized to determine ERL, dopamine (DAN), and uric acid (URA) simultaneously with the projected sensor.
    Plasma phosphorylated survivin levels in having BD patients were also downregulated compared to healthy individuals. Conclusion Analysis of PBMCs indicated increasing expression level of phosphorylated survivin in PBMCs of BD patients. There was also a downregulation in phosphorylated survivin levels in plasma of BD patients. © 2020 The Authors.Purpose Despite the discovery and synthesis of several anticancer drugs, cancer is still a major life threatening incident for human beings after cardiovascular diseases. Toxicity, severe side effects, and drug resistance are serious problems of available commercial anticancer drugs. Coumarins are synthetic and natural heterocycles that show promising antiproliferative activities against various tumors. The aim of this research is to computationally study the coumarin derivatives in order to develop reliable quantitative structure-activity relationship (QSAR) models for predicting their anticancer activities. Methods A data set of thirty one coumarin analogs with significant antiproliferative activities toward HepG2 cells were selected from the literature. The molecular descriptors for these compounds were calculated using Dragon, HyperChem, and ACD/Labs programs. Genetic algorithm (GA) accompanied by multiple linear regression (MLR) for simultaneous feature selection and model development was employed for generating the QSAR models. Results Based on the obtained results, the developed linear QSAR models with three and four descriptors showed good predictive power with r2 values of 0.670 and 0.692, respectively. Moreover, the calculated validation parameters for the models confirmed the reliability of the QSAR models. Conclusion The findings of the current study could be useful for the design and synthesis of novel anticancer drugs based on coumarin structure. © 2020 The Authors.Purpose Helicobacter pylori is recognized as one of the prevalent causes of human gastricinfection. In the present study, the role of mixed immunization with H. pylori lipopolysaccharide(LPS) and recombinant cytotoxin-associated gene A (rCagA) as a stimulator of host immuneresponses was determined. https://www.selleckchem.com/products/d609.html Methods BALB/c mice were immunized with different formulations by the systemic administrationat 14-day intervals. The effects of the formulations plus CpG adjuvants were assessed before andpost-immunization in separated studies. Moreover, the expression of Th1/Th2 cytokines wasquantified in sera of immunized mice using reverse transcription polymerase chain reaction (RTPCR)test and the protein levels confirmed with enzyme linked immunosorbent assay (ELISA).Finally, the specific antibody levels in sera were studied by ELISA and the tendency of cellularresponse was examined by IgG1/IgG2a ratio. Results Data of Western blotting verified the presence of constructed protein. Analysisof lymphocyte proliferation showed that CpG-conjugated rCagA increases lymphocytesproliferation compared to the control group. Also, it was shown that formulations containing LPSand rCagA promote a Th1 response indicated by interferon-gamma expression and induced Th1/Th2 balance. Additionally, the specific IgG1, total IgG and IgG2a levels elevated in response toall treatments. Ultimately, the IgG2a/IgG1 ratio in the mice immunized with rCagA-containingformulations increased. Conclusion These results indicated that rCagA protein carried with CpG adjuvant not onlymaintained its antigenicity throughout the experiment but also induced robust Th1-biasedimmune responses. Therefore, it holds promise for the production of an efficient vaccine against H. pylori infection. © 2020 The Authors.Purpose Due to the potential industrial and therapeutic applications of the yeast exopolysaccharides (EPSs), there has been an increasing demand to assess these biopolymers with improved characteristics. This study aimed to characterize the EPSs from Rhodosporidium babjevae (ATCC 90942 and IBRC-M 30088) as well as to evaluate their possible antioxidant, emulsifying and antiproliferative activities. Methods Rhodosporidium babjevae was cultured for 5 days and following isolation of supernatant, EPSs precipitated with adding of cold absolute ethanol and freeze-dried. The EPSs chemical structure was determined by FT-IR, SEM, HPLC-SEC and GC-MS. Additionally the solubility, water holding capacity and emulsifying activity of EPSs were evaluated. In vitro, antioxidant activity was investigated against DPPH, superoxide and hydroxyl radicals. Finally the EPSs consequence on the cell proliferation of human breast adenocarcinoma (MCF-7) and Madin-Darby canine kidney (MDCK) cell lines was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Results R. babjevae excreted 1.6±0.2 g/L of the EPSs. The EPSs had three fractions with molecular weights of 1.02 ×106 , 5×105 and 2×105 Da. Mannose and glucose were found as the main monosaccharides of the EPSs (8416 mol%, respectively). The EPSs exhibited emulsifying activity on sun flower oil. The scavenging activities were found to be dose-dependent and higher than hyaluronic acid. Significant difference among the EPSs treatments on the proliferation of MCF-7 and MDCK cell lines was not observed (P>0.05). Conclusion These results show the interesting potential of the EPSs from R. babjevae as biocompatible compounds for using in food and pharmaceutical fields. © 2020 The Authors.Purpose Estriol (ERL) is a type of hormone among the groups of estrogen hormone that was detected through the voltammetric technique by constructing an electrochemical sensor based on the octoxynol-9 modified graphite paste electrode (OXL-9MGPE). Methods Using the strategy of cyclic voltammetry (CV) and differential pulse voltammetry (DPV) with a bare graphite paste electrode (BGPE) immobilized with OXL-9, ERL electro-oxidation has been assessed in 0.2 M phosphate buffer solution (PBS) of pH 6.0. The fabricated electrode has substantial electrochemical sensing efficiency, and the ERL oxidation at the OXL-9MGPE was the irreversible process. The surface morphological characteristics of BGPE and OXL-9MGPE were differentiated with the help of field emission scanning electron microscopy (FE-SEM). Results The impact of various factors such as scan rate, pH, reproducibility, repeatability, and stability on the electro-oxidation of ERL was evaluated. Techniques of CV and DPV were utilized to determine ERL, dopamine (DAN), and uric acid (URA) simultaneously with the projected sensor.
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  • Background Checkpoint inhibitors (CKI) targeting PD-1 or PD-L1 are major therapies for the treatment of non-small cell lung cancer (NSCLC). Despite numerous studies of biological biomarkers, we currently lack a marker to predict CKI primary resistance. The aim of this study was to isolate clinical markers associated with the absence of efficacy of CKI used as monotherapy in NSCLC. Methods We conducted a retrospective analysis of 172 patients treated with anti-PD1 or anti-PDL1 monoclonal antibodies (mAb) for advanced NSCLC at the Dijon Cancer Center. Baseline characteristics were compared using the Chi squared test between responders and non-responders. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test for univariate analysis. Cox regression models were used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS). Results Among 172 patients included, 149 (86.5%) received CKI after platinum chemotherapy. Response rate (RR) was 16%, median progression-free survival (PFS) was 2.5 months (95% CI 0.7-30 months) and median overall survival (OS) was 10 months (95% CI 0.7-46.8 months). By univariate analysis, WHO performance status ≥ 1, presence of bone, liver and pleuroperitoneal metastasis were associated with poor PFS and OS. Multivariate analysis showed that only pleuroperitoneal metastasis was independently associated with PFS and OS. Patients with pleuroperitoneal metastasis and WHO performance status ≥ 1 had a less then 10% chance of yielding a benefit from CKI. Conclusions Our data support the hypothesis that pleuroperitoneal metastasis is a major predictive factor affecting CKI efficacy in NSCLC patients and may be used to avoid CKI monotherapy for such patients.Purpose COVID-19 is causing a lot of problems in health services around the world, especially in medical institutions receiving cancer patients. On March 12, China's National Health Commission announced that the peak of the COVID-19 epidemic has passed in China. Thus, a proper arrangement of medication, surgery and radiotherapy for patients with cancer is of vital importance after the epidemic peak. Methods A range of measures have been implemented in our center. Specific patients take priority for chemotherapy treatment. The amount of semi-elective and elective surgeries could be gradually increased beyond urgent and emergency surgery. The hypofractionated radiotherapy is recommended in the right circumstances. Results On March 13, our center announced that more than 5000 visits of chemotherapy and radiotherapy are arranged in our outpatient clinics and none of our patients and staffs have been diagnosed with COVID-19 as of March 28, 2020. Conclusion The rational arrangement we make now may be helpful to the future restoration of cancer treatments in other countries.Diffusion MRI fiber tracking datasets can contain millions of 3D streamlines, and their representation can weight tens of gigabytes of memory. These sets of streamlines are called tractograms and are often used for clinical operations or research. Their size makes them difficult to store, visualize, process or exchange over the network. We propose a new compression algorithm well-suited for tractograms, by taking advantage of the way streamlines are obtained with usual tracking algorithms. Our approach is based on unit vector quantization methods combined with a spatial transformation which results in low compression and decompression times, as well as a high compression ratio. For instance, a 11.5GB tractogram can be compressed to a 1.02GB file and decompressed in 11.3 seconds. https://www.selleckchem.com/products/acetalax-oxyphenisatin-acetate.html Moreover, our method allows for the compression and decompression of individual streamlines, reducing the need for a costly out-of-core algorithm with heavy datasets. Last, we open a way toward on-the-fly compression and decompression for handling larger datasets without needing a load of RAM (i.e. in-core handling), faster network exchanges and faster loading times for visualization or processing.Glucose transport is intimately linked to red blood cell physiology. Glucose is the unique energy source for these cells, and defects in glucose metabolism or transport activity are associated with impaired red blood cell morphology and deformability leading to reduced lifespan. In vertebrate erythrocytes, glucose transport is mediated by GLUT1 (in humans) or GLUT4 transporters. These proteins also account for dehydroascorbic acid (DHA) transport through erythrocyte membrane. The peculiarities of glucose transporters and the red blood cell pathologies involving GLUT1 are summarized in the present review.Purpose To investigate the frequency, magnitude and possible causes of frame-shifts that may occur between treatment planning and treatment delivery when performing Gamma Knife radiosurgery with rigid frame-based immobilization. Methods Differences between computed tomography (CT) framed fiducial stereotactic coordinate reference and cone beam computed tomography stereotactic coordinates after image registration were recorded for 49 frame-based GK radiosurgery cases performed using the Gamma Knife Icon. Parameters recorded include rotational shifts, translational shifts, and the GK-computed Maximum Shot Displacement (MSD) between the two stereotactic coordinate spaces. Other patient-specific parameters were collected and linear regression analysis was performed to evaluate predictors of increased displacement. Results The median values of rotational shifts were pitch 0.14°, yaw 0.17°, and roll 0.13°. The median absolute values of translational shifts were left-right 0.39 mm, anteroposterior 0.14 mm, and superior-inferior 0. 22 mm. The median value of MSD was 0.71 mm. Twelve cases (24.5%) had a MSD of greater than 1.0 mm. Male gender was associated with increased MSD (p = 0.013) and translational shifts (root-mean-squared value, p = 0.017). Cases with large differences between right and left sided pin lengths were also associated with increased MSD (p = 0.011). Conclusions The use of CBCT image guidance in frame-based GK radiosurgery allows unintended frame shifts to be identified and corrected. A significant fraction (24.5%) of patients had large enough shifts to result in a MSD of greater than 1.0 mm. Male gender and eccentrically placed frames were associated with increased MSD, and particular care should be taken in these cases.
    Background Checkpoint inhibitors (CKI) targeting PD-1 or PD-L1 are major therapies for the treatment of non-small cell lung cancer (NSCLC). Despite numerous studies of biological biomarkers, we currently lack a marker to predict CKI primary resistance. The aim of this study was to isolate clinical markers associated with the absence of efficacy of CKI used as monotherapy in NSCLC. Methods We conducted a retrospective analysis of 172 patients treated with anti-PD1 or anti-PDL1 monoclonal antibodies (mAb) for advanced NSCLC at the Dijon Cancer Center. Baseline characteristics were compared using the Chi squared test between responders and non-responders. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test for univariate analysis. Cox regression models were used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS). Results Among 172 patients included, 149 (86.5%) received CKI after platinum chemotherapy. Response rate (RR) was 16%, median progression-free survival (PFS) was 2.5 months (95% CI 0.7-30 months) and median overall survival (OS) was 10 months (95% CI 0.7-46.8 months). By univariate analysis, WHO performance status ≥ 1, presence of bone, liver and pleuroperitoneal metastasis were associated with poor PFS and OS. Multivariate analysis showed that only pleuroperitoneal metastasis was independently associated with PFS and OS. Patients with pleuroperitoneal metastasis and WHO performance status ≥ 1 had a less then 10% chance of yielding a benefit from CKI. Conclusions Our data support the hypothesis that pleuroperitoneal metastasis is a major predictive factor affecting CKI efficacy in NSCLC patients and may be used to avoid CKI monotherapy for such patients.Purpose COVID-19 is causing a lot of problems in health services around the world, especially in medical institutions receiving cancer patients. On March 12, China's National Health Commission announced that the peak of the COVID-19 epidemic has passed in China. Thus, a proper arrangement of medication, surgery and radiotherapy for patients with cancer is of vital importance after the epidemic peak. Methods A range of measures have been implemented in our center. Specific patients take priority for chemotherapy treatment. The amount of semi-elective and elective surgeries could be gradually increased beyond urgent and emergency surgery. The hypofractionated radiotherapy is recommended in the right circumstances. Results On March 13, our center announced that more than 5000 visits of chemotherapy and radiotherapy are arranged in our outpatient clinics and none of our patients and staffs have been diagnosed with COVID-19 as of March 28, 2020. Conclusion The rational arrangement we make now may be helpful to the future restoration of cancer treatments in other countries.Diffusion MRI fiber tracking datasets can contain millions of 3D streamlines, and their representation can weight tens of gigabytes of memory. These sets of streamlines are called tractograms and are often used for clinical operations or research. Their size makes them difficult to store, visualize, process or exchange over the network. We propose a new compression algorithm well-suited for tractograms, by taking advantage of the way streamlines are obtained with usual tracking algorithms. Our approach is based on unit vector quantization methods combined with a spatial transformation which results in low compression and decompression times, as well as a high compression ratio. For instance, a 11.5GB tractogram can be compressed to a 1.02GB file and decompressed in 11.3 seconds. https://www.selleckchem.com/products/acetalax-oxyphenisatin-acetate.html Moreover, our method allows for the compression and decompression of individual streamlines, reducing the need for a costly out-of-core algorithm with heavy datasets. Last, we open a way toward on-the-fly compression and decompression for handling larger datasets without needing a load of RAM (i.e. in-core handling), faster network exchanges and faster loading times for visualization or processing.Glucose transport is intimately linked to red blood cell physiology. Glucose is the unique energy source for these cells, and defects in glucose metabolism or transport activity are associated with impaired red blood cell morphology and deformability leading to reduced lifespan. In vertebrate erythrocytes, glucose transport is mediated by GLUT1 (in humans) or GLUT4 transporters. These proteins also account for dehydroascorbic acid (DHA) transport through erythrocyte membrane. The peculiarities of glucose transporters and the red blood cell pathologies involving GLUT1 are summarized in the present review.Purpose To investigate the frequency, magnitude and possible causes of frame-shifts that may occur between treatment planning and treatment delivery when performing Gamma Knife radiosurgery with rigid frame-based immobilization. Methods Differences between computed tomography (CT) framed fiducial stereotactic coordinate reference and cone beam computed tomography stereotactic coordinates after image registration were recorded for 49 frame-based GK radiosurgery cases performed using the Gamma Knife Icon. Parameters recorded include rotational shifts, translational shifts, and the GK-computed Maximum Shot Displacement (MSD) between the two stereotactic coordinate spaces. Other patient-specific parameters were collected and linear regression analysis was performed to evaluate predictors of increased displacement. Results The median values of rotational shifts were pitch 0.14°, yaw 0.17°, and roll 0.13°. The median absolute values of translational shifts were left-right 0.39 mm, anteroposterior 0.14 mm, and superior-inferior 0. 22 mm. The median value of MSD was 0.71 mm. Twelve cases (24.5%) had a MSD of greater than 1.0 mm. Male gender was associated with increased MSD (p = 0.013) and translational shifts (root-mean-squared value, p = 0.017). Cases with large differences between right and left sided pin lengths were also associated with increased MSD (p = 0.011). Conclusions The use of CBCT image guidance in frame-based GK radiosurgery allows unintended frame shifts to be identified and corrected. A significant fraction (24.5%) of patients had large enough shifts to result in a MSD of greater than 1.0 mm. Male gender and eccentrically placed frames were associated with increased MSD, and particular care should be taken in these cases.
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  • Conclusions CEUS has an excellent safety profile and shows a high diagnostic accuracy in assessing HCC compared with corresponding results from CT scans.Objective Measurement of positive end-expiratory pressure (PEEP)-induced recruitment lung volume using passive spirometry is based on the assumption that the functional residual capacity (FRC) is not modified by the PEEP changes. We aimed to investigate the influence of PEEP on FRC in different models of acute respiratory distress syndrome (ARDS). Methods A randomized crossover study was performed in 12 pigs. Pulmonary (n = 6) and extra-pulmonary (n = 6) ARDS models were established using an alveolar instillation of hydrochloric acid and a right atrium injection of oleic acid, respectively. Low (5 cmH2O) and high (15 cmH2O) PEEP were randomly applied in each animal. FRC and recruitment volume were determined using the nitrogen wash-in/wash-out technique and release maneuver. Results FRC was not significantly different between the two PEEP levels in either pulmonary ARDS (299 ± 92 mL and 309 ± 130 mL at 5 and 15 cmH2O, respectively) or extra-pulmonary ARDS (305 ± 143 mL and 328 ± 197 mL at 5 and 15 cmH2O, respectively). The recruitment volume was not significantly different between the two models (pulmonary, 341 ± 100 mL; extra-pulmonary, 351 ± 170 mL). Conclusions PEEP did not influence FRC in either the pulmonary or extra-pulmonary ARDS pig model.Introduction Yeast humanization, ranging from a simple point mutation to substitution of yeast gene(s) or even a complete pathway by human counterparts has enormously expanded yeast biomedical applications. Areas covered General and patent-oriented insights into the application of native and humanized yeasts for production of human glycoproteins (gps) and antibodies (Abs), toxicity/mutagenicity assays, treatments of gastrointestinal (GI) disorders and potential drug delivery as a probiotic (with emphasis on Saccharomyces bulardii) and studies on human diseases/cancers and screening effective drugs. Expert opinion Humanized yeasts cover the classical advantageous features of a 'microbial eukaryote' together with advanced human cellular processes. These unique characteristics would permit their use in the production of functional and stable therapeutic gps and Abs in lower prices compared to mammalian (CHO) production-based systems. Availability of yeasts humanized for cytochrome P450 s will expand their application in metabolism-related chemical toxicity assays. Engineered S. bulardii for expression of human proteins might expand its application by synergistically combining the probiotic activity with the treatment of metabolic diseases such as phenylketonuria via GI-delivery. Yeast models of human diseases will facilitate rapid functional/phenotypic characterization of the disease-producing mutant genes and screening of the therapeutic compounds using yeast-based high-throughput research techniques (Yeast one/two hybrid systems) and viability assays.Introduction The Coronavirus disease-19 (COVID-19) caused by the novel beta coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started in late December 2019 in Wuhan, China. Within a short span, COVID-19 was declared a global public health emergency affecting 214 countries with 5,939,234 confirmed cases and 3,67,255 deaths as of 30 May 2020. With limited knowledge about SARS-CoV-2, no approved treatment or vaccine is available till date. Areas covered We performed a review of literature on PubMed on the SARS-CoV-2 virus and COVID-19 illness including trials of preventive and therapeutic measures. This review presents the basic biology of coronaviruses, epidemiology of COVID-19, clinical presentations, investigational therapies and vaccines, infection prevention and control measures and the lessons from the present pandemic. Expert opinion The scale of the outbreak has brought the governments, health-care professionals, and scientists around the world under tremendous pressure to devise control strategies and develop novel prevention measures. While availability of vaccine for COVID-19 may take time, the disease may be contained through hand hygiene, physical distancing, travel restriction, and aggressive steps such as 'lockdown.' Clinical trials at different phases are ongoing across different countries to expedite the development of effective drugs and vaccine to overcome the pandemic.The clinical impact of pegfilgrastim in day-to-day practice remains unclear. This study evaluated the effectiveness of pegfilgrastim compared with daily filgrastim in patients with DLBCL who received the first-cycle of R-CHOP treatment by using a Japanese national inpatient database. Patient characteristics were adjusted by using propensity-score matching and stabilized inverse probability of treatment weighting (IPTW). In 1295 propensity-score-matched pairs, the incidence of febrile neutropenia was significantly lower in the pegfilgrastim group (risk difference 6.1%, 95% CI 4.1%-8.1%) than in the filgrastim group. In the pegfilgrastim group, the length of hospital stay and the total costs were also significantly reduced (percent reduction 34% [95% CI 31%-37%], percent reduction 12% [95% CI 9%-15%], respectively). The stabilized IPTW showed comparable results. In day-to-day practice, the simple mode of pegfilgrastim administration may be advantageous.Background There are current concerns about whether appropriate support is provided for sexual abuse and assault survivors. We reviewed the published evidence for peer-led groups in the care of survivors.Aims To determine the health and wellbeing outcomes of peer-led, group-based interventions for adult survivors who have experienced sexual abuse and assault and describe the experiences of participants attending these groups.Method Systematic review. The following databases were searched Medline, PsycINFO, Embase, Cochrane Library, Web of Science, Sociological Abstracts, IBSS. Papers focusing on adults using any research methodology were included. Quality appraisal was completed using the Mixed Methods Appraisal Tool (MMAT). Thematic analysis was undertaken using methods of constant comparison.Results Initial, and updated searches identified 16,724 potentially eligible articles. https://www.selleckchem.com/products/tj-m2010-5.html Of these, eight were included. Thematic analysis revealed that peer-led group-based interventions have positive impact on participants' psychological, physical and interpersonal well-being.
    Conclusions CEUS has an excellent safety profile and shows a high diagnostic accuracy in assessing HCC compared with corresponding results from CT scans.Objective Measurement of positive end-expiratory pressure (PEEP)-induced recruitment lung volume using passive spirometry is based on the assumption that the functional residual capacity (FRC) is not modified by the PEEP changes. We aimed to investigate the influence of PEEP on FRC in different models of acute respiratory distress syndrome (ARDS). Methods A randomized crossover study was performed in 12 pigs. Pulmonary (n = 6) and extra-pulmonary (n = 6) ARDS models were established using an alveolar instillation of hydrochloric acid and a right atrium injection of oleic acid, respectively. Low (5 cmH2O) and high (15 cmH2O) PEEP were randomly applied in each animal. FRC and recruitment volume were determined using the nitrogen wash-in/wash-out technique and release maneuver. Results FRC was not significantly different between the two PEEP levels in either pulmonary ARDS (299 ± 92 mL and 309 ± 130 mL at 5 and 15 cmH2O, respectively) or extra-pulmonary ARDS (305 ± 143 mL and 328 ± 197 mL at 5 and 15 cmH2O, respectively). The recruitment volume was not significantly different between the two models (pulmonary, 341 ± 100 mL; extra-pulmonary, 351 ± 170 mL). Conclusions PEEP did not influence FRC in either the pulmonary or extra-pulmonary ARDS pig model.Introduction Yeast humanization, ranging from a simple point mutation to substitution of yeast gene(s) or even a complete pathway by human counterparts has enormously expanded yeast biomedical applications. Areas covered General and patent-oriented insights into the application of native and humanized yeasts for production of human glycoproteins (gps) and antibodies (Abs), toxicity/mutagenicity assays, treatments of gastrointestinal (GI) disorders and potential drug delivery as a probiotic (with emphasis on Saccharomyces bulardii) and studies on human diseases/cancers and screening effective drugs. Expert opinion Humanized yeasts cover the classical advantageous features of a 'microbial eukaryote' together with advanced human cellular processes. These unique characteristics would permit their use in the production of functional and stable therapeutic gps and Abs in lower prices compared to mammalian (CHO) production-based systems. Availability of yeasts humanized for cytochrome P450 s will expand their application in metabolism-related chemical toxicity assays. Engineered S. bulardii for expression of human proteins might expand its application by synergistically combining the probiotic activity with the treatment of metabolic diseases such as phenylketonuria via GI-delivery. Yeast models of human diseases will facilitate rapid functional/phenotypic characterization of the disease-producing mutant genes and screening of the therapeutic compounds using yeast-based high-throughput research techniques (Yeast one/two hybrid systems) and viability assays.Introduction The Coronavirus disease-19 (COVID-19) caused by the novel beta coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started in late December 2019 in Wuhan, China. Within a short span, COVID-19 was declared a global public health emergency affecting 214 countries with 5,939,234 confirmed cases and 3,67,255 deaths as of 30 May 2020. With limited knowledge about SARS-CoV-2, no approved treatment or vaccine is available till date. Areas covered We performed a review of literature on PubMed on the SARS-CoV-2 virus and COVID-19 illness including trials of preventive and therapeutic measures. This review presents the basic biology of coronaviruses, epidemiology of COVID-19, clinical presentations, investigational therapies and vaccines, infection prevention and control measures and the lessons from the present pandemic. Expert opinion The scale of the outbreak has brought the governments, health-care professionals, and scientists around the world under tremendous pressure to devise control strategies and develop novel prevention measures. While availability of vaccine for COVID-19 may take time, the disease may be contained through hand hygiene, physical distancing, travel restriction, and aggressive steps such as 'lockdown.' Clinical trials at different phases are ongoing across different countries to expedite the development of effective drugs and vaccine to overcome the pandemic.The clinical impact of pegfilgrastim in day-to-day practice remains unclear. This study evaluated the effectiveness of pegfilgrastim compared with daily filgrastim in patients with DLBCL who received the first-cycle of R-CHOP treatment by using a Japanese national inpatient database. Patient characteristics were adjusted by using propensity-score matching and stabilized inverse probability of treatment weighting (IPTW). In 1295 propensity-score-matched pairs, the incidence of febrile neutropenia was significantly lower in the pegfilgrastim group (risk difference 6.1%, 95% CI 4.1%-8.1%) than in the filgrastim group. In the pegfilgrastim group, the length of hospital stay and the total costs were also significantly reduced (percent reduction 34% [95% CI 31%-37%], percent reduction 12% [95% CI 9%-15%], respectively). The stabilized IPTW showed comparable results. In day-to-day practice, the simple mode of pegfilgrastim administration may be advantageous.Background There are current concerns about whether appropriate support is provided for sexual abuse and assault survivors. We reviewed the published evidence for peer-led groups in the care of survivors.Aims To determine the health and wellbeing outcomes of peer-led, group-based interventions for adult survivors who have experienced sexual abuse and assault and describe the experiences of participants attending these groups.Method Systematic review. The following databases were searched Medline, PsycINFO, Embase, Cochrane Library, Web of Science, Sociological Abstracts, IBSS. Papers focusing on adults using any research methodology were included. Quality appraisal was completed using the Mixed Methods Appraisal Tool (MMAT). Thematic analysis was undertaken using methods of constant comparison.Results Initial, and updated searches identified 16,724 potentially eligible articles. https://www.selleckchem.com/products/tj-m2010-5.html Of these, eight were included. Thematic analysis revealed that peer-led group-based interventions have positive impact on participants' psychological, physical and interpersonal well-being.
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  • ay. Copyright © 2020 Yue Geng et al.Acacia polyacantha is a medicinal plant traditionally used to treat livestock diseases and gastrointestinal infections; our study was undertaken to evaluate the antistaphylococcal activities of the methanolic leaf, bark, and root extracts, fractions, and compounds from Acacia polyacantha against a panel of 14 multidrug-resistant Staphylococcus bacterial strains overexpressing efflux pumps. The study was also extended to investigate two possible modes of action, that is, influence on bacterial growth kinetics and influence on proton-ATPase pumps, of the most active compound against a reference strain. Materials and Methods. https://www.selleckchem.com/products/sp-600125.html The crude extracts after extraction were subjected to column chromatography. Antibacterial assays of extracts, fractions, and compounds alone and in the presence of efflux pump inhibitors were carried out using the broth microdilution method and the study of two mechanisms of action achieved by standard methods with the most active compound. Results. The phytochemical study of Acacia polyactivities of extracts, fractions, and compounds were improved in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) as an efflux pump inhibitor to as **** as >128 folds. Meanwhile, in the presence of chlorpromazine as an efflux pump inhibitor, only the activity of compound 10 was improved on 10 of the tested bacteria strains. Compound 4 prolonged the lag phase of the growth kinetic in a concentration-dependent manner and equally inhibited the proton-ATPase pumps of the tested bacteria strains. Conclusion. The present study demonstrates the antistaphylococcal potential of Acacia polyacantha and its constituents to combat bacterial infections alone or in combination with efflux pump inhibitors. Copyright © 2020 Fred A. Ashu et al.Si-Wu-Tang (SWT), a traditional Chinese herbal formula, has shown an effect on antibreast cancer. However, the mechanisms and bioactive components of SWT are still unclear. Fortunately, cell type-specific molecular network has provided an effective method. This study integrated the data of formula components, all types of biomolecules in the human body, and nonexpressed protein in breast cancer cells and constructed the breast cancer cell network and the biological network that SWT acted on the breast cancer-related targets by Entity Grammar System (EGS). Biological network showed 59 bioactive components acting on 15 breast cancer-related targets. The antibreast cancer mechanisms were summarized by enrichment analysis regulation of cell death, response to hormone stimulation, response to organic substance, regulation of phosphorylation of amino acids, regulation of cell proliferation, regulation of signal transmission, and affection of gland development. In addition, we discovered that verbascoside played the role of antibreast cancer by inhibiting cell proliferation, but there was not a report on this effect. The results of CCK8 and western blot were consistent with the antibreast cancer effect of verbascoside based on biological network. Biological network modeling by EGS and network analysis provide an effective way for uncovering the mechanism and identifying the bioactive components of SWT. Copyright © 2020 Baixia Zhang et al.Mutomo hill plant sanctuary is a ten-hectare piece of land in Kenya listed as a botanical garden under the Botanical Gardens Conservation International, originally established in 1964 with the aim of conserving indigenous flora from destructive anthropogenic activities. This paper presents ethnobotanical documentation of medicinal plants of Mutomo hill plant sanctuary and its environs. An ethnobotanical survey was carried out in Mutomo hill plant sanctuary and its environs with 48 herbalists aged between 32 and 96 years from July 2018 to February 2019 using a semistructured open-ended questionnaire. The plants were collected through random surveys with each herbalist in different ecotypes around the villages and within the Mutomo hill plant sanctuary. The Relative Frequency of Citation (RFC) for each species reported was calculated to determine the plant species frequently collected. In total, 68 different plant species distributed in 28 families and 54 genera were reported. The frequently used plant families were Leguminosae (13 species), Lamiaceae (6 species), and Euphorbiaceae (6 species). Shrubs (37%) and trees (34%) were the dominant growth habits reported. The most cited plant species were Cassia abbreviata Oliv. (RFC = 0.63), Acacia nilotica (L.). Delile (RFC = 0.54), Strychnos heningsii Gilg (RFC = 0.46), and Aloe secundiflora Engl. (RFC = 0.31). Root (19 species) and bark (19 species) were the frequently collected plant parts. Infectious diseases (33) and digestive system disorders (24) were reported to be managed with the majority of the plant species. This study contributes to safeguarding the traditional knowledge on medicinal plants in the study area, which is useful in appreciating and acknowledging the cultural heritage of the Kamba people from the local perspective of Mutomo area in Kenya. It also adds to the knowledge base and documentation of medicinal plants, which is useful information as potential data for drug development. Copyright © 2020 Fredrick Munyao Mutie et al.As the spectrum of diseases keeps changing and life pace keeps going faster, the probability and frequency of diseases caused by human inflammatory reactions also keep increasing. How to develop effective anti-inflammatory drugs has become the hotspot of researches. It has been found that alkaloids from Chinese medical herbs have anti-inflammatory, analgesic, antitumor, anticonvulsant, diuretic, and antiarrhythmic effects, among which the anti-inflammatory effect is very prominent and commonly used in the treatment of rheumatoid arthritis, ankylosing spondylitis, and other rheumatic immune diseases, but its mechanism of action has not been well explained. Based on this, this paper will classify alkaloids according to structural types and review the plant sources, applicable diseases, and anti-inflammatory mechanisms of 16 kinds of alkaloids commonly used in clinical treatment, such as berberine, tetrandrine, and stephanine, with the aim of providing a reference for drug researches and clinical applications. Copyright © 2020 Sicong Li et al.
    ay. Copyright © 2020 Yue Geng et al.Acacia polyacantha is a medicinal plant traditionally used to treat livestock diseases and gastrointestinal infections; our study was undertaken to evaluate the antistaphylococcal activities of the methanolic leaf, bark, and root extracts, fractions, and compounds from Acacia polyacantha against a panel of 14 multidrug-resistant Staphylococcus bacterial strains overexpressing efflux pumps. The study was also extended to investigate two possible modes of action, that is, influence on bacterial growth kinetics and influence on proton-ATPase pumps, of the most active compound against a reference strain. Materials and Methods. https://www.selleckchem.com/products/sp-600125.html The crude extracts after extraction were subjected to column chromatography. Antibacterial assays of extracts, fractions, and compounds alone and in the presence of efflux pump inhibitors were carried out using the broth microdilution method and the study of two mechanisms of action achieved by standard methods with the most active compound. Results. The phytochemical study of Acacia polyactivities of extracts, fractions, and compounds were improved in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) as an efflux pump inhibitor to as much as >128 folds. Meanwhile, in the presence of chlorpromazine as an efflux pump inhibitor, only the activity of compound 10 was improved on 10 of the tested bacteria strains. Compound 4 prolonged the lag phase of the growth kinetic in a concentration-dependent manner and equally inhibited the proton-ATPase pumps of the tested bacteria strains. Conclusion. The present study demonstrates the antistaphylococcal potential of Acacia polyacantha and its constituents to combat bacterial infections alone or in combination with efflux pump inhibitors. Copyright © 2020 Fred A. Ashu et al.Si-Wu-Tang (SWT), a traditional Chinese herbal formula, has shown an effect on antibreast cancer. However, the mechanisms and bioactive components of SWT are still unclear. Fortunately, cell type-specific molecular network has provided an effective method. This study integrated the data of formula components, all types of biomolecules in the human body, and nonexpressed protein in breast cancer cells and constructed the breast cancer cell network and the biological network that SWT acted on the breast cancer-related targets by Entity Grammar System (EGS). Biological network showed 59 bioactive components acting on 15 breast cancer-related targets. The antibreast cancer mechanisms were summarized by enrichment analysis regulation of cell death, response to hormone stimulation, response to organic substance, regulation of phosphorylation of amino acids, regulation of cell proliferation, regulation of signal transmission, and affection of gland development. In addition, we discovered that verbascoside played the role of antibreast cancer by inhibiting cell proliferation, but there was not a report on this effect. The results of CCK8 and western blot were consistent with the antibreast cancer effect of verbascoside based on biological network. Biological network modeling by EGS and network analysis provide an effective way for uncovering the mechanism and identifying the bioactive components of SWT. Copyright © 2020 Baixia Zhang et al.Mutomo hill plant sanctuary is a ten-hectare piece of land in Kenya listed as a botanical garden under the Botanical Gardens Conservation International, originally established in 1964 with the aim of conserving indigenous flora from destructive anthropogenic activities. This paper presents ethnobotanical documentation of medicinal plants of Mutomo hill plant sanctuary and its environs. An ethnobotanical survey was carried out in Mutomo hill plant sanctuary and its environs with 48 herbalists aged between 32 and 96 years from July 2018 to February 2019 using a semistructured open-ended questionnaire. The plants were collected through random surveys with each herbalist in different ecotypes around the villages and within the Mutomo hill plant sanctuary. The Relative Frequency of Citation (RFC) for each species reported was calculated to determine the plant species frequently collected. In total, 68 different plant species distributed in 28 families and 54 genera were reported. The frequently used plant families were Leguminosae (13 species), Lamiaceae (6 species), and Euphorbiaceae (6 species). Shrubs (37%) and trees (34%) were the dominant growth habits reported. The most cited plant species were Cassia abbreviata Oliv. (RFC = 0.63), Acacia nilotica (L.). Delile (RFC = 0.54), Strychnos heningsii Gilg (RFC = 0.46), and Aloe secundiflora Engl. (RFC = 0.31). Root (19 species) and bark (19 species) were the frequently collected plant parts. Infectious diseases (33) and digestive system disorders (24) were reported to be managed with the majority of the plant species. This study contributes to safeguarding the traditional knowledge on medicinal plants in the study area, which is useful in appreciating and acknowledging the cultural heritage of the Kamba people from the local perspective of Mutomo area in Kenya. It also adds to the knowledge base and documentation of medicinal plants, which is useful information as potential data for drug development. Copyright © 2020 Fredrick Munyao Mutie et al.As the spectrum of diseases keeps changing and life pace keeps going faster, the probability and frequency of diseases caused by human inflammatory reactions also keep increasing. How to develop effective anti-inflammatory drugs has become the hotspot of researches. It has been found that alkaloids from Chinese medical herbs have anti-inflammatory, analgesic, antitumor, anticonvulsant, diuretic, and antiarrhythmic effects, among which the anti-inflammatory effect is very prominent and commonly used in the treatment of rheumatoid arthritis, ankylosing spondylitis, and other rheumatic immune diseases, but its mechanism of action has not been well explained. Based on this, this paper will classify alkaloids according to structural types and review the plant sources, applicable diseases, and anti-inflammatory mechanisms of 16 kinds of alkaloids commonly used in clinical treatment, such as berberine, tetrandrine, and stephanine, with the aim of providing a reference for drug researches and clinical applications. Copyright © 2020 Sicong Li et al.
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  • omies in the non-episiotomy arm.BACKGROUND Pelvic floor disorders (PFDs), include urinary incontinence, overactive bladder, anal incontinence, and pelvic organ prolapse negatively affect physical, psychosocial, and economic wellbeing of women. In developing countries, less than a quarter of women with PFDs seek health care for their problem. Health care seeking for PFDs, and its associated factors, is little known in Ethiopia. This study aimed to assess health care seeking for PFDs, associated factors, and deterrents for seeking care. METHODS From a community based cross sectional study conducted form August 10 to September 4, 2016 to assess pelvic floor disorders, seven hundred four participants with PFDs drawn for health care seeking behavior analysis. Data were collected through interviewed administered questionnaire. Poisson regression model with robust variance was used to investigate the association of the independent variable with health care seeking behaviors. The results are reported in crude and adjusted prevalence ratio with 95% confidence intervals. RESULT Two hundred twenty five (32%; CI 26.8-35.5) women sought care for their PFDs. Majority 160 (71%) of them seek care from government health facilities. Middle wealth index Adjusted Prevalence Ratio (APR) = 1.4, CI 1.1, 1.8), autonomous decision making on own health (APR = 1.3, CI 1.1, 1.7), and sever impact of PFDs on quality of life (APR = 1.4, CI1.1, 1.9) were identified as associated factors for health care seeking. CONCLUSION A large number of women with pelvic floor disorder did not seek health care this calls for urgent and tailored intervention to enhance health care seeking behaviors of women with PFD.PURPOSE To evaluate the influence of cortical and cancellous bone structure on the biomechanical properties of all-suture and conventional anchors and compare the morphological bone damage after their failure. The hypothesis of the study is that all-suture anchor pullout is less invasive and that the pullout force is influenced by the cortical thickness. METHODS Thirty human humeri were biomechanically tested as follows starting with a load cycle from 20 to 50 N, a stepwise increase of the upper peak force by 0.05 N for each cycle at a rate of 1 Hz was performed. Analysis included maximum pullout strength for three different anchor implantation angles (45°, 90°, 110°) of the two anchor types. After anchor pullout, every sample underwent micro-CT analysis. Bone mineral density (BMD) and cortical thickness were determined at the anchor implantation site. Furthermore, the diameter of the cortical defect and the volume of the bone cavity were identified. RESULTS The maximum pullout strength of all-suture anchors preoperatively evaluated to decrease the risk of anchor failure.PURPOSE The purpose of this study was to compare the clinical and functional outcome scores following total knee arthroplasty (TKA) with two different systems. https://www.selleckchem.com/products/vx-561.html The hypothesis was that there is a difference between patients receiving the newer design than those receiving the predecessor. METHODS Two hundred patients who underwent TKA were randomized into two groups patients received either Attune TKA or PFC Sigma (both DePuy Synthes, Warsaw, IN). Clinically, the Knee Society Knee and Function Scores (KS and FS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Range of Motion (ROM) and Visual Analogue Scale (VAS) were evaluated and compared between the groups 2 years after surgery. 158 patients (80 in the Attune group and 78 in the PFC Sigma group) were available for follow-up. RESULTS Through bivariate analysis using parametric and non-parametric statistical tests, no significant differences in postoperative KS, FS, WOMAC, ROM or VAS between the two groups were detected. Both groups significantly improved regarding all evaluated endpoints 2 years after surgery. CONCLUSIONS In the current study population, no difference in clinical outcome between the two systems was found. The expected benefits of design modifications could not be observed in clinical outcome scores 2 years postoperatively. Both designs are effective options for improving pain and function in end-stage osteoarthritis. LEVEL OF EVIDENCE I.PURPOSE Preoperative assessment to determine the sizes of potential autografts is necessary for individualized anterior cruciate ligament reconstruction (ACLR). However, no study has investigated the prediction of the intraoperative diameter of the quadriceps tendon (QT) autograft based upon preoperative imaging. This study investigated the correlation between the intraoperative diameter of a QT autograft and in situ thickness or cross-sectional area (CSA) measured using preoperative MRI. METHODS Thirty-one knees of 31 patients (mean age 20.9 ± 5.0 years) who underwent individualized anatomic ACLR using all soft tissue QT autograft were included retrospectively. At 15 mm proximal to the superior pole of the patella, the maximum QT thickness was assessed in the sagittal plane and the CSA was assessed at the central 10 mm of the QT in the axial plane. The angle between the axial plane and a line perpendicular to the QT longitudinal axis was used to calculate an adjusted CSA using a cosine function. Intraoperatively, each QT autograft was harvested with 10 mm width and the diameter was measured using a graft sizing device. RESULTS Intra- and inter-observer reliabilities of all measurements using preoperative MRI were excellent (intra-class correlation coefficient, 0.833-0.970). Significant correlations were observed between the thickness, CSA, or adjusted CSA, and the intraoperative diameter (R = 0.434, 0.607, and 0.540, respectively; P  less then  0.05). CONCLUSIONS The CSA correlated most strongly with the QT autograft diameter. For individualized anatomic ACLR, measuring in situ CSA can be useful for preoperative planning of appropriate graft choices prior to surgery. LEVEL OF EVIDENCE III.PURPOSE The purpose of this study was to evaluate the relationship between patient-specific factors, preoperative radiographic findings, and the presence and severity of chondrolabral damage identified during hip arthroscopy for femoroacetabular impingement. METHODS Between 2014 and 2017, patients who underwent hip arthroscopy for FAI and labral tear were retrospectively reviewed. Patient-specific variables including age, gender, BMI, LCEA, and alpha angle were collected. Surgical reports were reviewed for labral tear position and size, as well as severity of acetabular and femoral chondromalacia. RESULTS There were 205 patients who met inclusion criteria with a mean age of 33 years (range 15-66), BMI 26.5 (range 15.9-44.5), LCEA 32.2° (range 21.0°-56.0°) and alpha angle 59.1° (range 33.0°-86.0°). Greater age (p = 0.023), alpha angle (p = 0.011) and male gender (p  less then  0.001) significantly correlated with high-grade acetabular chondral damage. Increased LCEA (p  less then  0.001), increased alpha angle (p = 0.
    omies in the non-episiotomy arm.BACKGROUND Pelvic floor disorders (PFDs), include urinary incontinence, overactive bladder, anal incontinence, and pelvic organ prolapse negatively affect physical, psychosocial, and economic wellbeing of women. In developing countries, less than a quarter of women with PFDs seek health care for their problem. Health care seeking for PFDs, and its associated factors, is little known in Ethiopia. This study aimed to assess health care seeking for PFDs, associated factors, and deterrents for seeking care. METHODS From a community based cross sectional study conducted form August 10 to September 4, 2016 to assess pelvic floor disorders, seven hundred four participants with PFDs drawn for health care seeking behavior analysis. Data were collected through interviewed administered questionnaire. Poisson regression model with robust variance was used to investigate the association of the independent variable with health care seeking behaviors. The results are reported in crude and adjusted prevalence ratio with 95% confidence intervals. RESULT Two hundred twenty five (32%; CI 26.8-35.5) women sought care for their PFDs. Majority 160 (71%) of them seek care from government health facilities. Middle wealth index Adjusted Prevalence Ratio (APR) = 1.4, CI 1.1, 1.8), autonomous decision making on own health (APR = 1.3, CI 1.1, 1.7), and sever impact of PFDs on quality of life (APR = 1.4, CI1.1, 1.9) were identified as associated factors for health care seeking. CONCLUSION A large number of women with pelvic floor disorder did not seek health care this calls for urgent and tailored intervention to enhance health care seeking behaviors of women with PFD.PURPOSE To evaluate the influence of cortical and cancellous bone structure on the biomechanical properties of all-suture and conventional anchors and compare the morphological bone damage after their failure. The hypothesis of the study is that all-suture anchor pullout is less invasive and that the pullout force is influenced by the cortical thickness. METHODS Thirty human humeri were biomechanically tested as follows starting with a load cycle from 20 to 50 N, a stepwise increase of the upper peak force by 0.05 N for each cycle at a rate of 1 Hz was performed. Analysis included maximum pullout strength for three different anchor implantation angles (45°, 90°, 110°) of the two anchor types. After anchor pullout, every sample underwent micro-CT analysis. Bone mineral density (BMD) and cortical thickness were determined at the anchor implantation site. Furthermore, the diameter of the cortical defect and the volume of the bone cavity were identified. RESULTS The maximum pullout strength of all-suture anchors preoperatively evaluated to decrease the risk of anchor failure.PURPOSE The purpose of this study was to compare the clinical and functional outcome scores following total knee arthroplasty (TKA) with two different systems. https://www.selleckchem.com/products/vx-561.html The hypothesis was that there is a difference between patients receiving the newer design than those receiving the predecessor. METHODS Two hundred patients who underwent TKA were randomized into two groups patients received either Attune TKA or PFC Sigma (both DePuy Synthes, Warsaw, IN). Clinically, the Knee Society Knee and Function Scores (KS and FS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Range of Motion (ROM) and Visual Analogue Scale (VAS) were evaluated and compared between the groups 2 years after surgery. 158 patients (80 in the Attune group and 78 in the PFC Sigma group) were available for follow-up. RESULTS Through bivariate analysis using parametric and non-parametric statistical tests, no significant differences in postoperative KS, FS, WOMAC, ROM or VAS between the two groups were detected. Both groups significantly improved regarding all evaluated endpoints 2 years after surgery. CONCLUSIONS In the current study population, no difference in clinical outcome between the two systems was found. The expected benefits of design modifications could not be observed in clinical outcome scores 2 years postoperatively. Both designs are effective options for improving pain and function in end-stage osteoarthritis. LEVEL OF EVIDENCE I.PURPOSE Preoperative assessment to determine the sizes of potential autografts is necessary for individualized anterior cruciate ligament reconstruction (ACLR). However, no study has investigated the prediction of the intraoperative diameter of the quadriceps tendon (QT) autograft based upon preoperative imaging. This study investigated the correlation between the intraoperative diameter of a QT autograft and in situ thickness or cross-sectional area (CSA) measured using preoperative MRI. METHODS Thirty-one knees of 31 patients (mean age 20.9 ± 5.0 years) who underwent individualized anatomic ACLR using all soft tissue QT autograft were included retrospectively. At 15 mm proximal to the superior pole of the patella, the maximum QT thickness was assessed in the sagittal plane and the CSA was assessed at the central 10 mm of the QT in the axial plane. The angle between the axial plane and a line perpendicular to the QT longitudinal axis was used to calculate an adjusted CSA using a cosine function. Intraoperatively, each QT autograft was harvested with 10 mm width and the diameter was measured using a graft sizing device. RESULTS Intra- and inter-observer reliabilities of all measurements using preoperative MRI were excellent (intra-class correlation coefficient, 0.833-0.970). Significant correlations were observed between the thickness, CSA, or adjusted CSA, and the intraoperative diameter (R = 0.434, 0.607, and 0.540, respectively; P  less then  0.05). CONCLUSIONS The CSA correlated most strongly with the QT autograft diameter. For individualized anatomic ACLR, measuring in situ CSA can be useful for preoperative planning of appropriate graft choices prior to surgery. LEVEL OF EVIDENCE III.PURPOSE The purpose of this study was to evaluate the relationship between patient-specific factors, preoperative radiographic findings, and the presence and severity of chondrolabral damage identified during hip arthroscopy for femoroacetabular impingement. METHODS Between 2014 and 2017, patients who underwent hip arthroscopy for FAI and labral tear were retrospectively reviewed. Patient-specific variables including age, gender, BMI, LCEA, and alpha angle were collected. Surgical reports were reviewed for labral tear position and size, as well as severity of acetabular and femoral chondromalacia. RESULTS There were 205 patients who met inclusion criteria with a mean age of 33 years (range 15-66), BMI 26.5 (range 15.9-44.5), LCEA 32.2° (range 21.0°-56.0°) and alpha angle 59.1° (range 33.0°-86.0°). Greater age (p = 0.023), alpha angle (p = 0.011) and male gender (p  less then  0.001) significantly correlated with high-grade acetabular chondral damage. Increased LCEA (p  less then  0.001), increased alpha angle (p = 0.
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  • BACKGROUND Increasing evidence has shown the beneficial effects of Rhodiola species on metabolic disorders, but their mechanisms are not clear. Hepatic steatosis is closely related to metabolic disorders, we aim to investigate the therapeutic effects of Rhodiola crenulata root (RCR) on fructose-induced hepatic steatosis and explore the underlying mechanisms. PURPOSE To observe the effect of Rhodiola crenulata root extract (RCR) on fructose-induced hepatic steatosis in Sprague-Dawley (SD) rats and explore its possible mechanism. METHODS Male Sprague-Dawley rats were treated with liquid fructose in their drinking water over 18 weeks. The extract of RCR was co-administered (once daily by oral gavage) during the last 5 weeks. Liver lipid deposition and morphological changes were observed by Oil red O staining. https://www.selleckchem.com/products/pf-04957325.html Real-time fluorescence quantitative PCR, Western blot and immunoprecipitation were used to detect gene and protein expression in liver. RESULTS RCR (50 mg/kg) reversed liquid fructose-induced increase in hesosome marker p62 in the livers of fructose-fed rats. CONCLUSIONS RCR has a certain improvement effect on fructose-induced hepatic steatosis, which is related to the activation of autophagy. Sawdust wastes were used as precursors to prepare adsorbents by combustion and pyrolysis for experimental and mechanism studies and determine the potential of biomass extracted from agro-industrial residues for Pb-polluted soil remediation. Pot experiments were conducted on contaminated soils near Pb-Zn mining with sawdust ash (SA) and sawdust biochar (SB) in different proportions and dosage ratios. Studies have indicated that the application of biomass materials can enhance the adsorption, complexation and precipitation of Pb cations in soil and reduce the mobility of Pb. The concentrations of SPLP-Pb and DTPA-extractable Pb in amended soils were the lowest under 1% 12 and 5% 11 treatment, respectively. Results of fraction extraction and XANES analysis showed that the materials change the main forms of Pb in soil. Moreover, the binding behavior of Pb with organic matter increases the proportion of Pb (Ac)2, leading to the transformation of high toxicity Pb-compounds into precipitates and complexes. The remediation methods of 2% 12 and 5% 12 were better than those of other methods in stabilizing Pb in soil. This study indicated that heat-treated sawdust can be used for Pb-polluted soil remediation, which is a type of environmental remediation measure with considerable ecological potential. BACKGROUND Among preterm infants, neurodevelopmental outcomes are influenced by both medical and sociodemographic factors. Less is known about the impact on these factors on neonatal neurobehavioral patterns. OBJECTIVE To determine associations between demographic, psychosocial and medical risk factors and neonatal neurobehavior. METHODS Multi-center observational study of infants born less then 30 weeks enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study between April 2014-May 2016. Maternal medical, demographic, and psychological variables and infant medical variables were prospectively collected. Demographic, substance, psychological and medical risk indices were developed. Neurobehavioral assessment was performed using the NICU Network Neurobehavioral Scale (NNNS) at NICU discharge. RESULTS 709 infants were enrolled in the NOVI study, and for 679 infants with neurobehavioral assessments, 6 NNNS behavioral profiles were calculated using latent profile analysis. Profile 6 infants (n = 47/679, 7%) were atypical, having poor attention, self-regulation and movement quality, hypertonia and increased stress signs. After adjustment for site, profile 6 infants had significantly smaller head circumferences at birth (β -0.87; -1.59, -0.14), and higher rates of late sepsis (OR 3.38; CI 1.66, 6.92) compared to Profiles 1-5 infants. There were no significant differences in other neonatal morbidities between the two groups. Profile 6 infants had a higher prenatal demographic risk score (1.46 vs 1.07;β 0.34; CI 0.06, 0.61) compared to Profiles 1-5 infants. CONCLUSION NNNS behavioral profiles identify an atypical behavioral pattern that is associated with early influences of demographic and medical variables. Such behavioral patterns may be seen as early as NICU discharge. Cells of the facultative photosynthetic bacterium Rhodobacter capsulatus exploit the simultaneous presence in the cultural medium of the toxic oxyanion tellurite (TeO32-) and the redox mediator lawsone (2-hydroxy-1,4-naphthoquinone) by reducing tellurite to metal Te0 nanoprecipitates (TeNPs) outside the cells. Here we have studied the mechanism by which lawsone interacts with metabolically active cells and analysed both structure and composition of the TeNPs collected from the growth medium of phototrophycally grown R. capsulatus. High Resolution Transmission Electron Microscopy (HR-TEM) images and Energy-Dispersive X-ray (EDX) microanalysis of TeNPs showed a central core of polycrystalline tellurium interspersed in an organic matrix with a predominant protein-based composition. The main proteins from Te0 nanostructures were identified by Liquid Chromatography tandem-Mass Spectrometry and were all correlated with the cell outer membrane composition. The interaction of reduced lawsone with tellurite and with the bacterial cells was probed by Cyclic Voltammetry and Scanning ElectroChemical Microscopy (SECM). We concluded that lawsone is required for the reduction of tellurite to metal Te0 in a reaction mechanism dependent on reducing equivalents deriving from the cell photosynthetic metabolism. SECM experiments demonstrate that lawsone, by diffusing inside the bacterial cells, is effectively available at the membrane site of the photosynthetic electron transport chain. V.Alterations in the NRF2/KEAP1 pathway result in the constitutive activation of NRF2, leading to the aberrant induction of antioxidant and detoxification enzymes, including NQO1. The NQO1 bioactivatable agent β-lapachone can target cells with high NQO1 expression but relies in the generation of reactive oxygen species (ROS), which are actively scavenged in cells with NRF2/KEAP1 mutations. However, whether NRF2/KEAP1 mutations influence the response to β-lapachone treatment remains unknown. To address this question, we assessed the cytotoxicity of β-lapachone in a panel of NSCLC cell lines bearing either wild-type or mutant KEAP1. We found that, despite overexpression of NQO1, KEAP1 mutant cells were resistant to β-lapachone due to enhanced detoxification of ROS, which prevented DNA damage and cell death. To evaluate whether specific inhibition of the NRF2-regulated antioxidant enzymes could abrogate resistance to β-lapachone, we systematically inhibited the four major antioxidant cellular systems using genetic and/or pharmacologic approaches.
    BACKGROUND Increasing evidence has shown the beneficial effects of Rhodiola species on metabolic disorders, but their mechanisms are not clear. Hepatic steatosis is closely related to metabolic disorders, we aim to investigate the therapeutic effects of Rhodiola crenulata root (RCR) on fructose-induced hepatic steatosis and explore the underlying mechanisms. PURPOSE To observe the effect of Rhodiola crenulata root extract (RCR) on fructose-induced hepatic steatosis in Sprague-Dawley (SD) rats and explore its possible mechanism. METHODS Male Sprague-Dawley rats were treated with liquid fructose in their drinking water over 18 weeks. The extract of RCR was co-administered (once daily by oral gavage) during the last 5 weeks. Liver lipid deposition and morphological changes were observed by Oil red O staining. https://www.selleckchem.com/products/pf-04957325.html Real-time fluorescence quantitative PCR, Western blot and immunoprecipitation were used to detect gene and protein expression in liver. RESULTS RCR (50 mg/kg) reversed liquid fructose-induced increase in hesosome marker p62 in the livers of fructose-fed rats. CONCLUSIONS RCR has a certain improvement effect on fructose-induced hepatic steatosis, which is related to the activation of autophagy. Sawdust wastes were used as precursors to prepare adsorbents by combustion and pyrolysis for experimental and mechanism studies and determine the potential of biomass extracted from agro-industrial residues for Pb-polluted soil remediation. Pot experiments were conducted on contaminated soils near Pb-Zn mining with sawdust ash (SA) and sawdust biochar (SB) in different proportions and dosage ratios. Studies have indicated that the application of biomass materials can enhance the adsorption, complexation and precipitation of Pb cations in soil and reduce the mobility of Pb. The concentrations of SPLP-Pb and DTPA-extractable Pb in amended soils were the lowest under 1% 12 and 5% 11 treatment, respectively. Results of fraction extraction and XANES analysis showed that the materials change the main forms of Pb in soil. Moreover, the binding behavior of Pb with organic matter increases the proportion of Pb (Ac)2, leading to the transformation of high toxicity Pb-compounds into precipitates and complexes. The remediation methods of 2% 12 and 5% 12 were better than those of other methods in stabilizing Pb in soil. This study indicated that heat-treated sawdust can be used for Pb-polluted soil remediation, which is a type of environmental remediation measure with considerable ecological potential. BACKGROUND Among preterm infants, neurodevelopmental outcomes are influenced by both medical and sociodemographic factors. Less is known about the impact on these factors on neonatal neurobehavioral patterns. OBJECTIVE To determine associations between demographic, psychosocial and medical risk factors and neonatal neurobehavior. METHODS Multi-center observational study of infants born less then 30 weeks enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study between April 2014-May 2016. Maternal medical, demographic, and psychological variables and infant medical variables were prospectively collected. Demographic, substance, psychological and medical risk indices were developed. Neurobehavioral assessment was performed using the NICU Network Neurobehavioral Scale (NNNS) at NICU discharge. RESULTS 709 infants were enrolled in the NOVI study, and for 679 infants with neurobehavioral assessments, 6 NNNS behavioral profiles were calculated using latent profile analysis. Profile 6 infants (n = 47/679, 7%) were atypical, having poor attention, self-regulation and movement quality, hypertonia and increased stress signs. After adjustment for site, profile 6 infants had significantly smaller head circumferences at birth (β -0.87; -1.59, -0.14), and higher rates of late sepsis (OR 3.38; CI 1.66, 6.92) compared to Profiles 1-5 infants. There were no significant differences in other neonatal morbidities between the two groups. Profile 6 infants had a higher prenatal demographic risk score (1.46 vs 1.07;β 0.34; CI 0.06, 0.61) compared to Profiles 1-5 infants. CONCLUSION NNNS behavioral profiles identify an atypical behavioral pattern that is associated with early influences of demographic and medical variables. Such behavioral patterns may be seen as early as NICU discharge. Cells of the facultative photosynthetic bacterium Rhodobacter capsulatus exploit the simultaneous presence in the cultural medium of the toxic oxyanion tellurite (TeO32-) and the redox mediator lawsone (2-hydroxy-1,4-naphthoquinone) by reducing tellurite to metal Te0 nanoprecipitates (TeNPs) outside the cells. Here we have studied the mechanism by which lawsone interacts with metabolically active cells and analysed both structure and composition of the TeNPs collected from the growth medium of phototrophycally grown R. capsulatus. High Resolution Transmission Electron Microscopy (HR-TEM) images and Energy-Dispersive X-ray (EDX) microanalysis of TeNPs showed a central core of polycrystalline tellurium interspersed in an organic matrix with a predominant protein-based composition. The main proteins from Te0 nanostructures were identified by Liquid Chromatography tandem-Mass Spectrometry and were all correlated with the cell outer membrane composition. The interaction of reduced lawsone with tellurite and with the bacterial cells was probed by Cyclic Voltammetry and Scanning ElectroChemical Microscopy (SECM). We concluded that lawsone is required for the reduction of tellurite to metal Te0 in a reaction mechanism dependent on reducing equivalents deriving from the cell photosynthetic metabolism. SECM experiments demonstrate that lawsone, by diffusing inside the bacterial cells, is effectively available at the membrane site of the photosynthetic electron transport chain. V.Alterations in the NRF2/KEAP1 pathway result in the constitutive activation of NRF2, leading to the aberrant induction of antioxidant and detoxification enzymes, including NQO1. The NQO1 bioactivatable agent β-lapachone can target cells with high NQO1 expression but relies in the generation of reactive oxygen species (ROS), which are actively scavenged in cells with NRF2/KEAP1 mutations. However, whether NRF2/KEAP1 mutations influence the response to β-lapachone treatment remains unknown. To address this question, we assessed the cytotoxicity of β-lapachone in a panel of NSCLC cell lines bearing either wild-type or mutant KEAP1. We found that, despite overexpression of NQO1, KEAP1 mutant cells were resistant to β-lapachone due to enhanced detoxification of ROS, which prevented DNA damage and cell death. To evaluate whether specific inhibition of the NRF2-regulated antioxidant enzymes could abrogate resistance to β-lapachone, we systematically inhibited the four major antioxidant cellular systems using genetic and/or pharmacologic approaches.
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