Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bi...Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.展开更多
Aircraft final assembly line(AFAL)involves thousands of processes that must be completed before delivery.However,the heavy reliance on manual labor in most assembly processes affects the quality and prolongs the deliv...Aircraft final assembly line(AFAL)involves thousands of processes that must be completed before delivery.However,the heavy reliance on manual labor in most assembly processes affects the quality and prolongs the delivery time.While the advent of artificial intelligence of things(AIoT)technologies has introduced advancements in certain AFAL scenarios,systematically enhancing the intelligence level of the AFAL and promoting the widespread deployment of artificial intelligence(AI)technologies remain significant challenges.To address these challenges,we propose the intelligent and collaborative aircraft assembly(ICAA)framework,which integrates AI technologies within a cloud-edge-terminal architecture.The ICAA framework is designed to support AI-enabled applications in the AFAL,with the goal of improving assembly efficiency at both individual and multiple process levels.We analyze specific demands across various assembly scenarios and introduce corresponding AI technologies to meet these demands.The three-tier ICAA framework consists of the assembly field,edge data platform,and assembly cloud platform,facilitating the collection of heterogeneous terminal data and the deployment of AI technologies.The framework enhances assembly efficiency by reducing reliance on manual labor for individual processes and fostering collaboration across multiple processes.We provide detailed descriptions of how AI functions at each level of the framework.Furthermore,we apply the ICAA framework to a real AFAL,focusing explicitly on the flight control system testing process.This practical implementation demonstrates the effectiveness of the framework in improving assembly efficiency and promoting the adoption of AIoT technologies.展开更多
Hantaviruses,such as Hantaan virus(HTNV)and Seoul virus,are the causative agents of Hantavirus cardiopulmonary syndrome(HCPS)and hemorrhagic fever with renal syndrome(HFRS),and are important zoonotic pathogens.China h...Hantaviruses,such as Hantaan virus(HTNV)and Seoul virus,are the causative agents of Hantavirus cardiopulmonary syndrome(HCPS)and hemorrhagic fever with renal syndrome(HFRS),and are important zoonotic pathogens.China has the highest incidence of HFRS,which is mainly caused by HTNV and Seoul virus.No approved antiviral drugs are available for these hantaviral diseases.Here,a chemiluminescence-based highthroughput-screening(HTS)assay was developed and used to screen HTNV pseudovirus(HTNVpv)inhibitors in a library of 1813 approved drugs and 556 small-molecule compounds from traditional Chinese medicine sources.We identified six compounds with in vitro anti-HTNVpvactivities in the low-micromolar range(EC50values of0.1–2.2μmol/L;selectivity index of 40–900).Among the six selected compounds,cepharanthine not only showed good anti-HTNVpvactivity in vitro but also inhibited HTNVpv-fluc infection in Balb/c mice 5 h after infection by94%(180 mg/kg/d,P<0.01),93%(90 mg/kg/d,P<0.01),or 92%(45 mg/kg/d,P<0.01),respectively,in a bioluminescent imaging mouse model.A time-of-addition analysis suggested that the antiviral mechanism of cepharanthine involves the membrane fusion and entry phases.Overall,we have established a HTS method for antiviral drugs screening,and shown that cepharanthine is a candidate for HCPS and HFRS therapy.These findings may offer a starting point for the treatment of patients infected with hantaviruses.展开更多
基金the Project for Sci-ence and Technology Plan of Liaoning Province(No.2011225020).
文摘Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.
基金supported in part by the National Natural Science Foundation of China under Grants 92167205,61933009,62025305,and 62103268.
文摘Aircraft final assembly line(AFAL)involves thousands of processes that must be completed before delivery.However,the heavy reliance on manual labor in most assembly processes affects the quality and prolongs the delivery time.While the advent of artificial intelligence of things(AIoT)technologies has introduced advancements in certain AFAL scenarios,systematically enhancing the intelligence level of the AFAL and promoting the widespread deployment of artificial intelligence(AI)technologies remain significant challenges.To address these challenges,we propose the intelligent and collaborative aircraft assembly(ICAA)framework,which integrates AI technologies within a cloud-edge-terminal architecture.The ICAA framework is designed to support AI-enabled applications in the AFAL,with the goal of improving assembly efficiency at both individual and multiple process levels.We analyze specific demands across various assembly scenarios and introduce corresponding AI technologies to meet these demands.The three-tier ICAA framework consists of the assembly field,edge data platform,and assembly cloud platform,facilitating the collection of heterogeneous terminal data and the deployment of AI technologies.The framework enhances assembly efficiency by reducing reliance on manual labor for individual processes and fostering collaboration across multiple processes.We provide detailed descriptions of how AI functions at each level of the framework.Furthermore,we apply the ICAA framework to a real AFAL,focusing explicitly on the flight control system testing process.This practical implementation demonstrates the effectiveness of the framework in improving assembly efficiency and promoting the adoption of AIoT technologies.
基金National Science and Technology Major Projects of Infectious Disease(grant number 2018ZX10731101)。
文摘Hantaviruses,such as Hantaan virus(HTNV)and Seoul virus,are the causative agents of Hantavirus cardiopulmonary syndrome(HCPS)and hemorrhagic fever with renal syndrome(HFRS),and are important zoonotic pathogens.China has the highest incidence of HFRS,which is mainly caused by HTNV and Seoul virus.No approved antiviral drugs are available for these hantaviral diseases.Here,a chemiluminescence-based highthroughput-screening(HTS)assay was developed and used to screen HTNV pseudovirus(HTNVpv)inhibitors in a library of 1813 approved drugs and 556 small-molecule compounds from traditional Chinese medicine sources.We identified six compounds with in vitro anti-HTNVpvactivities in the low-micromolar range(EC50values of0.1–2.2μmol/L;selectivity index of 40–900).Among the six selected compounds,cepharanthine not only showed good anti-HTNVpvactivity in vitro but also inhibited HTNVpv-fluc infection in Balb/c mice 5 h after infection by94%(180 mg/kg/d,P<0.01),93%(90 mg/kg/d,P<0.01),or 92%(45 mg/kg/d,P<0.01),respectively,in a bioluminescent imaging mouse model.A time-of-addition analysis suggested that the antiviral mechanism of cepharanthine involves the membrane fusion and entry phases.Overall,we have established a HTS method for antiviral drugs screening,and shown that cepharanthine is a candidate for HCPS and HFRS therapy.These findings may offer a starting point for the treatment of patients infected with hantaviruses.
