As natural killer(NK)cells eliminate cancer cells and virus-infected cells,as well as modulate various other medical conditions,including aging-associated conditions such as neurodegenerative disorders,understanding N...As natural killer(NK)cells eliminate cancer cells and virus-infected cells,as well as modulate various other medical conditions,including aging-associated conditions such as neurodegenerative disorders,understanding NK cell regulation is of considerable clinical importance.This article reviews the role of circadian processes(melatonin and the cortisol system),aryl hydrocarbon receptor,and vagal nerve in the modulation of NK cell function,highlighting the importance of the endogenous mitochondrial melatonergic pathway in NK cells.As circadian and exogenous melatonin increase NK cell cytotoxicity,the presence of the endogenous melatonergic pathway may be of some importance not only to NK function and immune checkpoint regulation but also from the efflux of melatonin,which decreases tumor cell survival,proliferation,and metastasis,as well as decreasing immune checkpoint ligands,such as programmed cell ligand 1(PD-L1).NK cell melatonergic pathway regulation may therefore have significant impacts not only on NK cell cytotoxicity but also on the intercellular interactions within tumors and other pathological microenvironments.As melatonin has anti-viral effects,the regulation of the NK cell melatonergic pathway can have wider impacts on how NK cells regulate viral infections,including in the course of viral-induced susceptibility to neurodegenerative conditions.Recent data indicate that the endogenous melatonergic pathway is regulated by interactions of signal transducer and activator of transcription(STAT)3 and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)dimer composition.As both STAT3 and NF-κB dimer composition modulate NK cells,their interaction in the modulation of the NK cell melatonergic pathway will be important to determine.This has significant future research and treatment implications,including improving the clinical efficacy of current treatment approaches such as immune checkpoint inhibition and chimeric antigen receptor(CAR)NK cell therapy,and may accelerate a means of preventing cancer.展开更多
1.Introduction Data inference(DInf)is a data security threat in which critical information is inferred from low-sensitivity data.Once regarded as an advanced professional threat limited to intelligence analysts,DInf h...1.Introduction Data inference(DInf)is a data security threat in which critical information is inferred from low-sensitivity data.Once regarded as an advanced professional threat limited to intelligence analysts,DInf has become a widespread risk in the artificial intelligence(AI)era.展开更多
Metro systems are important transport infrastructures in megacities,and their long-term operational safety is challenged by frequent external disturbances,such as environmental extremes and human construction activ-it...Metro systems are important transport infrastructures in megacities,and their long-term operational safety is challenged by frequent external disturbances,such as environmental extremes and human construction activ-ities.A metro system must be resilient to resist,adapt to,and recover its performance when such disruptions occur.Current studies on metro system resilience often lack a comprehensive view from a complex system perspective,leading to a plethora of choices for methods of analysis and indicators applied to different metro systems and external disturbances.Therefore,the present paper aims to provide a comprehensive review of the topics and works revolving around the resilience of metro systems.It first clarifies the concept of metro system resilience based on classical definitions from a technical perspective.Metro resilience encompasses both the structural and operational aspects of metro systems,including their damage mechanisms,analysis methods and indicators of resilience.Methods for enhancing metro system resilience across structural,operational and monitoring dimensions are explored.Finally,future research directions are discussed,emphasizing the impor-tance of considering the"system of systems"formed by interdependent infrastructure,refining uncertainty analysis,and investigating the opportunities arising from the application of artificial intelligence for improving metro system resilience against external disturbances.展开更多
文摘As natural killer(NK)cells eliminate cancer cells and virus-infected cells,as well as modulate various other medical conditions,including aging-associated conditions such as neurodegenerative disorders,understanding NK cell regulation is of considerable clinical importance.This article reviews the role of circadian processes(melatonin and the cortisol system),aryl hydrocarbon receptor,and vagal nerve in the modulation of NK cell function,highlighting the importance of the endogenous mitochondrial melatonergic pathway in NK cells.As circadian and exogenous melatonin increase NK cell cytotoxicity,the presence of the endogenous melatonergic pathway may be of some importance not only to NK function and immune checkpoint regulation but also from the efflux of melatonin,which decreases tumor cell survival,proliferation,and metastasis,as well as decreasing immune checkpoint ligands,such as programmed cell ligand 1(PD-L1).NK cell melatonergic pathway regulation may therefore have significant impacts not only on NK cell cytotoxicity but also on the intercellular interactions within tumors and other pathological microenvironments.As melatonin has anti-viral effects,the regulation of the NK cell melatonergic pathway can have wider impacts on how NK cells regulate viral infections,including in the course of viral-induced susceptibility to neurodegenerative conditions.Recent data indicate that the endogenous melatonergic pathway is regulated by interactions of signal transducer and activator of transcription(STAT)3 and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)dimer composition.As both STAT3 and NF-κB dimer composition modulate NK cells,their interaction in the modulation of the NK cell melatonergic pathway will be important to determine.This has significant future research and treatment implications,including improving the clinical efficacy of current treatment approaches such as immune checkpoint inhibition and chimeric antigen receptor(CAR)NK cell therapy,and may accelerate a means of preventing cancer.
基金supported by the National Key Research and Development Program of China(2022YFB2703503)the National Natural Science Foundation of China(62293501,62525210,and 62293502)the China Scholarship Council(202306280318).
文摘1.Introduction Data inference(DInf)is a data security threat in which critical information is inferred from low-sensitivity data.Once regarded as an advanced professional threat limited to intelligence analysts,DInf has become a widespread risk in the artificial intelligence(AI)era.
基金supported by National Key R&D Program of China 2024YFC3808804National Natural Science Foundation of China NO.52478411+1 种基金China Scholarship Council No.202506260003Jinan Rail Transit Group Co.,Ltd(ggjn-sd-gd2022008fw).
文摘Metro systems are important transport infrastructures in megacities,and their long-term operational safety is challenged by frequent external disturbances,such as environmental extremes and human construction activ-ities.A metro system must be resilient to resist,adapt to,and recover its performance when such disruptions occur.Current studies on metro system resilience often lack a comprehensive view from a complex system perspective,leading to a plethora of choices for methods of analysis and indicators applied to different metro systems and external disturbances.Therefore,the present paper aims to provide a comprehensive review of the topics and works revolving around the resilience of metro systems.It first clarifies the concept of metro system resilience based on classical definitions from a technical perspective.Metro resilience encompasses both the structural and operational aspects of metro systems,including their damage mechanisms,analysis methods and indicators of resilience.Methods for enhancing metro system resilience across structural,operational and monitoring dimensions are explored.Finally,future research directions are discussed,emphasizing the impor-tance of considering the"system of systems"formed by interdependent infrastructure,refining uncertainty analysis,and investigating the opportunities arising from the application of artificial intelligence for improving metro system resilience against external disturbances.
