Accurate prediction of tropical cyclone(TC)intensity is challenging due to the complex physical processes involved.Here,we introduce a new TC intensity prediction scheme for the western North Pacific(WNP)based on a ti...Accurate prediction of tropical cyclone(TC)intensity is challenging due to the complex physical processes involved.Here,we introduce a new TC intensity prediction scheme for the western North Pacific(WNP)based on a time-dependent theory of TC intensification,termed the energetically based dynamical system(EBDS)model,together with the use of a long short-term memory(LSTM)neural network.In time-dependent theory,TC intensity change is controlled by both the internal dynamics of the TC system and various environmental factors,expressed as environmental dynamical efficiency.The LSTM neural network is used to predict the environmental dynamical efficiency in the EBDS model trained using besttrack TC data and global reanalysis data during 1982–2017.The transfer learning and ensemble methods are used to retrain the scheme using the environmental factors predicted by the Global Forecast System(GFS)of the National Centers for Environmental Prediction during 2017–21.The predicted environmental dynamical efficiency is finally iterated into the EBDS equations to predict TC intensity.The new scheme is evaluated for TC intensity prediction using both reanalysis data and the GFS prediction data.The intensity prediction by the new scheme shows better skill than the official prediction from the China Meteorological Administration(CMA)and those by other state-of-art statistical and dynamical forecast systems,except for the 72-h forecast.Particularly at the longer lead times of 96 h and 120 h,the new scheme has smaller forecast errors,with a more than 30%improvement over the official forecasts.展开更多
Human UDP-glycosyltransferases(UGTs)are responsible for the glycosylation of a wide variety of endogenous substrates and commonly prescribed drugs.Different genetic polymorphisms in UGT genes are implicated in interin...Human UDP-glycosyltransferases(UGTs)are responsible for the glycosylation of a wide variety of endogenous substrates and commonly prescribed drugs.Different genetic polymorphisms in UGT genes are implicated in interindividual differences in drug response and cancer risk.However,the genetic complexity beyond these variants has not been comprehensively assessed.We here leveraged wholeexome and whole-genome sequencing data from 141,456 unrelated individuals across 7 major human populations to provide a comprehensive profile of genetic variability across the human UGT gene family.Overall,9666 exonic variants were observed,of which 98.9%were rare.To interpret the functional impact of UGT missense variants,we developed a gene family-specific variant effect predictor.This algorithm identified a total of 1208 deleterious variants,most of which were found in African and South Asian populations.Structural analysis corroborated the predicted effects for multiple variations in substrate binding sites.Combined,our analyses provide a systematic overview of UGT variability,which can yield insights into interindividual differences in phase 2 metabolism and facilitate the translation of sequencing data into personalized predictions of UGT substrate disposition.展开更多
Effective electrochemical conversion of CO_(2) to value-added liquid multi-carbon products driven by renewable energy is a promising approach to alleviate excessive CO_(2) emission and achieve large-scale renewable en...Effective electrochemical conversion of CO_(2) to value-added liquid multi-carbon products driven by renewable energy is a promising approach to alleviate excessive CO_(2) emission and achieve large-scale renewable energy storage.However,the selectivity and catalytic activity towards liquid multi-carbon products of CO_(2) electroreduction reaction are still unsatisfactory due to the sluggish C-C coupling process and the formation of complex oxygen-containing intermediates.Hence,designing and fabricating highly effective electrocatalysts is crucial for practical applications in this field.Here,we developed Cl-modified Cu catalyst(Cu-Cl)for efficient electrochemical reduction of CO_(2) to ethanol.The optimal Faradaic efficiency and partial current density of ethanol on the Cu-Cl sample reached 26.2%and 343.2 mA·cm^(-2) at-0.74 V(vs.reversible hydrogen electrode(RHE)),which were 1.66 and 1.76 times higher than those of the catalyst without Cl decoration,outperforming those in most previously reported works.Density functional theory(DFT)calculations revealed that the Cl-modified Cu surface suppressed the parasitic hydrogen evolution reaction(HER)and reduced the energy barrier for the C-C coupling process,making the formation of key intermediates favorable for ethanol production.Thus,the decoration of Cl on the Cu surface facilitated ethanol formation.展开更多
Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide,but the molecular basis underlying its development remains unclear.An accumulating body of evidence supports gasdermin D(G...Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide,but the molecular basis underlying its development remains unclear.An accumulating body of evidence supports gasdermin D(GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases.However,there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis.In this work,we investigated the role of GSDMD-mediated pyroptosis in silicosis.Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression.Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica.Measurement of interleukin-1βrelease,lactic dehydrogenase activity,and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages.Additionally,we verified that both canonical(caspase-1-mediated)and non-canonical(caspase-4/5/11-mediated)signaling pathways mediated silica-induced pyroptosis activation,in vivo and in vitro.Notably,Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes,which highlighted the pivotal role of pyroptosis in this disease.Taken together,our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.展开更多
Dear Editor,The coronavirus disease 2019(COVID-19)pandemic,which is caused by SARS-Co V-2,has gained serious attention from medical practitioners around the world in the past few months.Approximately 20%of critically ...Dear Editor,The coronavirus disease 2019(COVID-19)pandemic,which is caused by SARS-Co V-2,has gained serious attention from medical practitioners around the world in the past few months.Approximately 20%of critically ill COVID-19 patients were reported to have suffered myocardial injury.The specific mechanism of this pathology requires further investigation(Yang et al.,2020).展开更多
Vibrio cholerae,the causative agent of the infectious disease,cholera,is commonly found in brackish waters and infects human hosts via the fecal-oral route.V.cholerae is a master of stress resistance as V.cholerae’s ...Vibrio cholerae,the causative agent of the infectious disease,cholera,is commonly found in brackish waters and infects human hosts via the fecal-oral route.V.cholerae is a master of stress resistance as V.cholerae’s dynamic lifestyle across different physical environments constantly exposes it to diverse stressful circumstances.Specifically,V.cholerae has dedicated genetic regulatory networks to sense different environmental cues and respond to these signals.With frequent outbreaks costing a tremendous amount of lives and increased global water temperatures providing more suitable aquatic habitats for V.cholerae,cholera pandemics remain a probable catastrophic threat to humanity.Understanding how V.cholerae copes with different environmental stresses broadens our repertoire of measures against infectious diseases and expands our general knowledge of prokaryotic stress responses.In this review,we summarize the regulatory mechanisms of how V.cholerae fights against stresses in vivo and in vitro.展开更多
基金supported by the National Key R&D Program of China(Grant No.2017YFC1501604)the National Natural Science Foundation of China(Grant Nos.41875114 and 41875057).
文摘Accurate prediction of tropical cyclone(TC)intensity is challenging due to the complex physical processes involved.Here,we introduce a new TC intensity prediction scheme for the western North Pacific(WNP)based on a time-dependent theory of TC intensification,termed the energetically based dynamical system(EBDS)model,together with the use of a long short-term memory(LSTM)neural network.In time-dependent theory,TC intensity change is controlled by both the internal dynamics of the TC system and various environmental factors,expressed as environmental dynamical efficiency.The LSTM neural network is used to predict the environmental dynamical efficiency in the EBDS model trained using besttrack TC data and global reanalysis data during 1982–2017.The transfer learning and ensemble methods are used to retrain the scheme using the environmental factors predicted by the Global Forecast System(GFS)of the National Centers for Environmental Prediction during 2017–21.The predicted environmental dynamical efficiency is finally iterated into the EBDS equations to predict TC intensity.The new scheme is evaluated for TC intensity prediction using both reanalysis data and the GFS prediction data.The intensity prediction by the new scheme shows better skill than the official prediction from the China Meteorological Administration(CMA)and those by other state-of-art statistical and dynamical forecast systems,except for the 72-h forecast.Particularly at the longer lead times of 96 h and 120 h,the new scheme has smaller forecast errors,with a more than 30%improvement over the official forecasts.
基金support from the Swedish Research Council(grant numbers 2021-02801 and 2023-03015)Cancerfonden(grant23-0763 PT)+2 种基金by the SciLifeLab and Wallenberg National Program for Data-Driven Life Science(grant WASPDDLS22:006)the Robert Bosch Foundation,Stuttgart,Germany and from the National Autonomous University of Mexico(UNAM)DGECI program Initiation to Research 2023supported in part by the South African Medical Research Council(SAMRC)。
文摘Human UDP-glycosyltransferases(UGTs)are responsible for the glycosylation of a wide variety of endogenous substrates and commonly prescribed drugs.Different genetic polymorphisms in UGT genes are implicated in interindividual differences in drug response and cancer risk.However,the genetic complexity beyond these variants has not been comprehensively assessed.We here leveraged wholeexome and whole-genome sequencing data from 141,456 unrelated individuals across 7 major human populations to provide a comprehensive profile of genetic variability across the human UGT gene family.Overall,9666 exonic variants were observed,of which 98.9%were rare.To interpret the functional impact of UGT missense variants,we developed a gene family-specific variant effect predictor.This algorithm identified a total of 1208 deleterious variants,most of which were found in African and South Asian populations.Structural analysis corroborated the predicted effects for multiple variations in substrate binding sites.Combined,our analyses provide a systematic overview of UGT variability,which can yield insights into interindividual differences in phase 2 metabolism and facilitate the translation of sequencing data into personalized predictions of UGT substrate disposition.
基金sponsored by Natural Science Foundation of Shanghai(No.22JC1404200)Double First-class Initiative Fund of ShanghaiTech University.
文摘Effective electrochemical conversion of CO_(2) to value-added liquid multi-carbon products driven by renewable energy is a promising approach to alleviate excessive CO_(2) emission and achieve large-scale renewable energy storage.However,the selectivity and catalytic activity towards liquid multi-carbon products of CO_(2) electroreduction reaction are still unsatisfactory due to the sluggish C-C coupling process and the formation of complex oxygen-containing intermediates.Hence,designing and fabricating highly effective electrocatalysts is crucial for practical applications in this field.Here,we developed Cl-modified Cu catalyst(Cu-Cl)for efficient electrochemical reduction of CO_(2) to ethanol.The optimal Faradaic efficiency and partial current density of ethanol on the Cu-Cl sample reached 26.2%and 343.2 mA·cm^(-2) at-0.74 V(vs.reversible hydrogen electrode(RHE)),which were 1.66 and 1.76 times higher than those of the catalyst without Cl decoration,outperforming those in most previously reported works.Density functional theory(DFT)calculations revealed that the Cl-modified Cu surface suppressed the parasitic hydrogen evolution reaction(HER)and reduced the energy barrier for the C-C coupling process,making the formation of key intermediates favorable for ethanol production.Thus,the decoration of Cl on the Cu surface facilitated ethanol formation.
基金supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMSNos.2021-1-I2M-049 and 2018-I2M-1-001,China)+1 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Nos.2019RC330001 and 2021RC310002,China)National Natural Science Foundation of China(No.82090010)。
文摘Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide,but the molecular basis underlying its development remains unclear.An accumulating body of evidence supports gasdermin D(GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases.However,there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis.In this work,we investigated the role of GSDMD-mediated pyroptosis in silicosis.Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression.Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica.Measurement of interleukin-1βrelease,lactic dehydrogenase activity,and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages.Additionally,we verified that both canonical(caspase-1-mediated)and non-canonical(caspase-4/5/11-mediated)signaling pathways mediated silica-induced pyroptosis activation,in vivo and in vitro.Notably,Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes,which highlighted the pivotal role of pyroptosis in this disease.Taken together,our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.
基金financially supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(201812M-1-001)Consulting Research Project of Chinese Academy of Engineering(2020-KYGG-01-05)。
文摘Dear Editor,The coronavirus disease 2019(COVID-19)pandemic,which is caused by SARS-Co V-2,has gained serious attention from medical practitioners around the world in the past few months.Approximately 20%of critically ill COVID-19 patients were reported to have suffered myocardial injury.The specific mechanism of this pathology requires further investigation(Yang et al.,2020).
基金NIH grants(Grant numbers:AI120489,AI157106 and AI137283).
文摘Vibrio cholerae,the causative agent of the infectious disease,cholera,is commonly found in brackish waters and infects human hosts via the fecal-oral route.V.cholerae is a master of stress resistance as V.cholerae’s dynamic lifestyle across different physical environments constantly exposes it to diverse stressful circumstances.Specifically,V.cholerae has dedicated genetic regulatory networks to sense different environmental cues and respond to these signals.With frequent outbreaks costing a tremendous amount of lives and increased global water temperatures providing more suitable aquatic habitats for V.cholerae,cholera pandemics remain a probable catastrophic threat to humanity.Understanding how V.cholerae copes with different environmental stresses broadens our repertoire of measures against infectious diseases and expands our general knowledge of prokaryotic stress responses.In this review,we summarize the regulatory mechanisms of how V.cholerae fights against stresses in vivo and in vitro.