Infectious pandemics result in hundreds and millions of deaths,notable examples of the Spanish Flu,the Black Death and smallpox.The current pandemic,caused by SARS-CoV-2(severe acute respiratory syndrome coronavirus 2...Infectious pandemics result in hundreds and millions of deaths,notable examples of the Spanish Flu,the Black Death and smallpox.The current pandemic,caused by SARS-CoV-2(severe acute respiratory syndrome coronavirus 2),is unprecedented even in the historical term of pandemics.The unprecedentedness is featured by multiple surges,rapid identification of therapeutic options and accelerated development of vaccines.Remdesivir,originally developed for Ebola viral disease,is the first treatment of COVID-19(Coronavirus disease 2019)approved by the United States Food and Drug Administration.As demonstrated by in vitro and preclinical studies,this therapeutic agent is highly potent with a broad spectrum activity against viruses from as many as seven families even cross species.However,randomized controlled trials have failed to confirm the efficacy and safety.Remdesivir improves some clinical signs but not critical parameters such as mortality.This antiviral agent is an ester/phosphorylation prodrug and excessive hydrolysis which increases cellular toxicity.Remdesivir is given intravenously,leading to concentration spikes and likely increasing the potential of hydrolysis-based toxicity.This review has proposed a conceptual framework for improving its efficacy and minimizing toxicity not only for the COVID-19 pandemic but also for future ones caused by remdesivir-sensitive viruses.展开更多
Limited aerobic scope(AS)during digestion might be the main constraint on the performance of bodily functions in water-breathing animals.Thus,investigating the postprandial changes in various physiological functions a...Limited aerobic scope(AS)during digestion might be the main constraint on the performance of bodily functions in water-breathing animals.Thus,investigating the postprandial changes in various physiological functions and determining the existence of a shared common pattern because of possible dependence on residual AS during digestion in freshwaterfish species are very important in conservation physiology.All species from slow-flow habitats showed impaired swimming speed while digesting,whereas all species from fast-flow habitats showed strong swimming performance,which was unchanged while digesting.Only two species from slow-flow habitats showed impaired heat tolerance during digestion,suggesting that whether oxygen limitation is involved in the heat tolerance process is species-specific.Three species from slow-or intermediate-flow habitats showed impaired hypoxia tolerance during digestion because feeding metabolism cannot cease completely under hypoxia.Overall,there was no common pattern in postprandial changes in different physiological functions because:(1)the digestion process was suppressed under oxygen-limiting conditions,(2)the residual AS decreased during digestion,and(3)performance was related to residual AS,while digestion was context-dependent and species-specific.However,digestion generally showed a stronger effect on bodily functions in species from slow-flow habitats,whereas it showed no impairment infishes from fast-flow habitats.Nevertheless,the postprandial change in physiological functions varies with habitat,possibly due to divergent selective pressure on such functions.More importantly,the present study suggests that a precise prediction of how freshwaterfish populations will respond to global climate change needs to incorporate data from postprandialfishes.展开更多
基金supported by National Institutes of Health Grants R01 EB018748,R21 Al153031University of Cincinnati Cancer Center(Yan,B).
文摘Infectious pandemics result in hundreds and millions of deaths,notable examples of the Spanish Flu,the Black Death and smallpox.The current pandemic,caused by SARS-CoV-2(severe acute respiratory syndrome coronavirus 2),is unprecedented even in the historical term of pandemics.The unprecedentedness is featured by multiple surges,rapid identification of therapeutic options and accelerated development of vaccines.Remdesivir,originally developed for Ebola viral disease,is the first treatment of COVID-19(Coronavirus disease 2019)approved by the United States Food and Drug Administration.As demonstrated by in vitro and preclinical studies,this therapeutic agent is highly potent with a broad spectrum activity against viruses from as many as seven families even cross species.However,randomized controlled trials have failed to confirm the efficacy and safety.Remdesivir improves some clinical signs but not critical parameters such as mortality.This antiviral agent is an ester/phosphorylation prodrug and excessive hydrolysis which increases cellular toxicity.Remdesivir is given intravenously,leading to concentration spikes and likely increasing the potential of hydrolysis-based toxicity.This review has proposed a conceptual framework for improving its efficacy and minimizing toxicity not only for the COVID-19 pandemic but also for future ones caused by remdesivir-sensitive viruses.
基金funded by the National Natural Science Foundation of China(31172096,31670418)the Science and Technology Research Program of Chongqing Municipal Education Commission(KJQN201900534,KJQN202000538).
文摘Limited aerobic scope(AS)during digestion might be the main constraint on the performance of bodily functions in water-breathing animals.Thus,investigating the postprandial changes in various physiological functions and determining the existence of a shared common pattern because of possible dependence on residual AS during digestion in freshwaterfish species are very important in conservation physiology.All species from slow-flow habitats showed impaired swimming speed while digesting,whereas all species from fast-flow habitats showed strong swimming performance,which was unchanged while digesting.Only two species from slow-flow habitats showed impaired heat tolerance during digestion,suggesting that whether oxygen limitation is involved in the heat tolerance process is species-specific.Three species from slow-or intermediate-flow habitats showed impaired hypoxia tolerance during digestion because feeding metabolism cannot cease completely under hypoxia.Overall,there was no common pattern in postprandial changes in different physiological functions because:(1)the digestion process was suppressed under oxygen-limiting conditions,(2)the residual AS decreased during digestion,and(3)performance was related to residual AS,while digestion was context-dependent and species-specific.However,digestion generally showed a stronger effect on bodily functions in species from slow-flow habitats,whereas it showed no impairment infishes from fast-flow habitats.Nevertheless,the postprandial change in physiological functions varies with habitat,possibly due to divergent selective pressure on such functions.More importantly,the present study suggests that a precise prediction of how freshwaterfish populations will respond to global climate change needs to incorporate data from postprandialfishes.
