Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical pro...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.展开更多
This paper explores the evolution of geoscientific inquiry,tracing the progression from traditional physics-based models to modern data-driven approaches facilitated by significant advancements in artificial intellige...This paper explores the evolution of geoscientific inquiry,tracing the progression from traditional physics-based models to modern data-driven approaches facilitated by significant advancements in artificial intelligence(AI)and data collection techniques.Traditional models,which are grounded in physical and numerical frameworks,provide robust explanations by explicitly reconstructing underlying physical processes.However,their limitations in comprehensively capturing Earth’s complexities and uncertainties pose challenges in optimization and real-world applicability.In contrast,contemporary data-driven models,particularly those utilizing machine learning(ML)and deep learning(DL),leverage extensive geoscience data to glean insights without requiring exhaustive theoretical knowledge.ML techniques have shown promise in addressing Earth science-related questions.Nevertheless,challenges such as data scarcity,computational demands,data privacy concerns,and the“black-box”nature of AI models hinder their seamless integration into geoscience.The integration of physics-based and data-driven methodologies into hybrid models presents an alternative paradigm.These models,which incorporate domain knowledge to guide AI methodologies,demonstrate enhanced efficiency and performance with reduced training data requirements.This review provides a comprehensive overview of geoscientific research paradigms,emphasizing untapped opportunities at the intersection of advanced AI techniques and geoscience.It examines major methodologies,showcases advances in large-scale models,and discusses the challenges and prospects that will shape the future landscape of AI in geoscience.The paper outlines a dynamic field ripe with possibilities,poised to unlock new understandings of Earth’s complexities and further advance geoscience exploration.展开更多
Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was in- creased after the aut...Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was in- creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradually reducing over time. Western blotting demonstrated that protein levels of light chain 3-11 and cathepsin B were significantly in- creased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, in- jection of 3-methyladenine significantly diminished light chain 3-11 and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cells can be eliminated through upregulating cell autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cells. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.展开更多
基金National Key R&D Program of China(2017YFB0202600 and 2020YFC0841400)National Natural Science Foundation of China(91742109,8152204,31770978,81773674,and 21877134)+8 种基金National Health&Medical Research of Australia(1080321,1143976 and 1150425)Science Foundation of Guangzhou City(201904020023,China)Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme(2016 and 2019,China)Guangdong Provincial Key Laboratory of Construction Foundation(2017B030314030,China)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y093,China)Zhejiang University special scientific research fund for COVID-19 prevention and control(China)National Health&Medical Research of Australia(1080321,1143976,and 1150425)Taikang Insurance Group Co.,Ltd.Beijing Taikang Yicai Foundation(Beijing,China)
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection can cause acute respiratory distress syndrome,hypercoagulability,hypertension,and multiorgan dysfunction.Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis.In an analysis of a randomly collected cohort of 124 patients with COVID-19,we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity.By virtual screening of a U.S.FDA approved drug library,we identified an anticoagulation agent dipyridamole(DIP)in silico,which suppressed SARS-CoV-2 replication in vitro.In a proof-of-concept trial involving 31 patients with COVID-19,DIP supplementation was associated with significantly decreased concentrations of D-dimers(P<0.05),increased lymphocyte and platelet recovery in the circulation,and markedly improved clinical outcomes in comparison to the control patients.In particular,all 8 of the DIP-treated severely ill patients showed remarkable improvement:7 patients(87.5%)achieved clinical cure and were discharged from the hospitals while the remaining 1 patient(12.5%)was in clinical remission.
基金supported by National Natural Science Foundation of China(T2225019,41925007,62372470,U21A2013,42201415,42022054,42241109,42077156,52121006,42090014,and 42325107)the National Key R&D Programme of China(2022YFF0500)+2 种基金the Youth Innovation Promotion Association CAS(2023112)the Strategic Priority Research Program of CAS(XDA23090303)the RECLAIM Network Plus(EP/W034034/1).
文摘This paper explores the evolution of geoscientific inquiry,tracing the progression from traditional physics-based models to modern data-driven approaches facilitated by significant advancements in artificial intelligence(AI)and data collection techniques.Traditional models,which are grounded in physical and numerical frameworks,provide robust explanations by explicitly reconstructing underlying physical processes.However,their limitations in comprehensively capturing Earth’s complexities and uncertainties pose challenges in optimization and real-world applicability.In contrast,contemporary data-driven models,particularly those utilizing machine learning(ML)and deep learning(DL),leverage extensive geoscience data to glean insights without requiring exhaustive theoretical knowledge.ML techniques have shown promise in addressing Earth science-related questions.Nevertheless,challenges such as data scarcity,computational demands,data privacy concerns,and the“black-box”nature of AI models hinder their seamless integration into geoscience.The integration of physics-based and data-driven methodologies into hybrid models presents an alternative paradigm.These models,which incorporate domain knowledge to guide AI methodologies,demonstrate enhanced efficiency and performance with reduced training data requirements.This review provides a comprehensive overview of geoscientific research paradigms,emphasizing untapped opportunities at the intersection of advanced AI techniques and geoscience.It examines major methodologies,showcases advances in large-scale models,and discusses the challenges and prospects that will shape the future landscape of AI in geoscience.The paper outlines a dynamic field ripe with possibilities,poised to unlock new understandings of Earth’s complexities and further advance geoscience exploration.
基金supported by grants from the National Natural Science Foundation of China,No.31171014 and No.30970869the Project of Science and Technology Commission of ShanghaiCity,No.09DZ1950400+2 种基金Board of Health of Shanghai,China,No.2008086the Youth Projects of National Natural Science Foundation of China,No.31100783Youth Key Project in Shanghai College of Medicine of Fudan University,No.09-L37
文摘Autophagy is involved in neural cell death after cerebral ischemia. Our previous studies showed that rapamycin-induced autophagy decreased the rate of apoptosis, but the rate of apoptosis was in- creased after the autophagy inhibitor, 3-methyladenine, was used. In this study, a suture-occluded method was performed to generate a rat model of brain ischemia. Under a transmission electron microscope, autophagic bodies and autophagy lysosomes were markedly accumulated in neurons at 4 hours post brain ischemic injury, with their numbers gradually reducing over time. Western blotting demonstrated that protein levels of light chain 3-11 and cathepsin B were significantly in- creased within 4 hours of ischemic injury, but these levels were not persistently upregulated over time. Confocal microscopy showed that autophagy was mainly found in neurons with positive light chain 3 signal. Injection of rapamycin via tail vein promoted the occurrence of autophagy in rat brain tissue after cerebral ischemia and elevated light chain 3 and cathepsin B expression. However, in- jection of 3-methyladenine significantly diminished light chain 3-11 and cathepsin B expression. Results verified that autophagic and lysosomal activity is increased in ischemic neurons. Abnormal components in cells can be eliminated through upregulating cell autophagy or inhibiting autophagy after ischemic brain injury, resulting in a dynamic balance of substances in cells. Moreover, drugs that interfere with autophagy may be potential therapies for the treatment of brain injury.
