The ongoing coronavirus epidemic,including the novel coronavirus(SARS-CoV-2),continues to pose a significant threat to global public health.Host targets address multiple stages of the viral life cycle and provide dive...The ongoing coronavirus epidemic,including the novel coronavirus(SARS-CoV-2),continues to pose a significant threat to global public health.Host targets address multiple stages of the viral life cycle and provide diverse opportunities for therapeutic interventions.This study identified sorting nexin 10(SNX10)as a facilitator of replication of human coronavirus OC43(HCoV-OC43),underscoring its potential as a novel antiviral target.The knockout of SNX10 significantly suppressed HCoV-OC43 replication both in vivo and in vitro.Immunoprecipitation-mass spectrometry(IP-MS)analysis identified the adaptor protein complex 2 subunitμ1(AP2M1)as a direct interactor of SNX10.Specifically,SNX10 facilitates phosphorylation of the AP2M1,thereby enhancing clathrin-mediated viral endocytosis.Furthermore,subsequent binding and internalization assays revealed that SNX10 knockout significantly inhibits viral entry into host cells.Conversely,the reconstitution of SNX10 fully restored viral entry,thereby confirming the critical and indispensable role of SNX10 in pathogen internalization.Simultaneously,SNX10 was identified as a key factor that promotes endosomal acidification by modulating pH levels,which in turn facilitated the release of the viral genome.Notably,the ablation of SNX10 was found to trigger autophagy activation during infection,thereby maintaining intracellular homeostasis.Additionally,it exerted autonomous antiviral effects through lysosomal degradation pathways.Collectively,these findings demonstrate SNX10 serves as a pivotal regulator of the viral life cycle and underscore its therapeutic potential as a multi-faceted antiviral candidate target capable of simultaneously inhibiting viral internalization,viral genomic release,and hostpathogen equilibrium.展开更多
To the Editor:Despite advancements in combinational antiretroviral treatment for HIV-1,cognitive impairments are still experienced by over 50%of acquired immunodeficiency syndrome patients1.Unlike other classical form...To the Editor:Despite advancements in combinational antiretroviral treatment for HIV-1,cognitive impairments are still experienced by over 50%of acquired immunodeficiency syndrome patients1.Unlike other classical forms of neurologic dementia such as Alzheimer’s disease,HIV-associated neurocognitive disorder(HAND)predominantly manifests in younger individuals with HIV infection,which is categorized into asymptomatic neurocognitive impairment,mild neurocognitive disorder,and severe HIV-associated dementia,necessitating urgent development of effective diagnosis and treatment.展开更多
As part of China's "the Belt and Road"strategy, China Railway Express provides alternative shipping routes and transportation modes from Asia to Europe and creates new opportunities for intermodal transp...As part of China's "the Belt and Road"strategy, China Railway Express provides alternative shipping routes and transportation modes from Asia to Europe and creates new opportunities for intermodal transportation in the shipping industry. A time–distancebased cost(time cost) function was proposed to compare China Railway Express with traditional transportation modes. Time cost was related to different types of cargoes,which exhibit distinct sensitivity to time. Using the proposed cost function as basis, we identified the cost indifference area where total costs are equal. Further analysis was performed for selecting the transportation mode and supply area for a specific cargo. This study provides various parties, such as business owners, the government, and the shipping industry, with many valuable insights.展开更多
基金supported by the National Natural Science Foundation(82130101)the Major Scientific and Technological Projects of Guangdong Province(2023B1111050008)the Post Scientist Fund awarded by the Chinese Academy of Traditional Chinese Medicine(ZZ13035-02)to Shuwen Liu.Regional Joint Foundation of Basic and Applied Basic Research in Guangdong Province(2023A1515111165)to Chan Yang.
文摘The ongoing coronavirus epidemic,including the novel coronavirus(SARS-CoV-2),continues to pose a significant threat to global public health.Host targets address multiple stages of the viral life cycle and provide diverse opportunities for therapeutic interventions.This study identified sorting nexin 10(SNX10)as a facilitator of replication of human coronavirus OC43(HCoV-OC43),underscoring its potential as a novel antiviral target.The knockout of SNX10 significantly suppressed HCoV-OC43 replication both in vivo and in vitro.Immunoprecipitation-mass spectrometry(IP-MS)analysis identified the adaptor protein complex 2 subunitμ1(AP2M1)as a direct interactor of SNX10.Specifically,SNX10 facilitates phosphorylation of the AP2M1,thereby enhancing clathrin-mediated viral endocytosis.Furthermore,subsequent binding and internalization assays revealed that SNX10 knockout significantly inhibits viral entry into host cells.Conversely,the reconstitution of SNX10 fully restored viral entry,thereby confirming the critical and indispensable role of SNX10 in pathogen internalization.Simultaneously,SNX10 was identified as a key factor that promotes endosomal acidification by modulating pH levels,which in turn facilitated the release of the viral genome.Notably,the ablation of SNX10 was found to trigger autophagy activation during infection,thereby maintaining intracellular homeostasis.Additionally,it exerted autonomous antiviral effects through lysosomal degradation pathways.Collectively,these findings demonstrate SNX10 serves as a pivotal regulator of the viral life cycle and underscore its therapeutic potential as a multi-faceted antiviral candidate target capable of simultaneously inhibiting viral internalization,viral genomic release,and hostpathogen equilibrium.
基金supported by Natural Science Foundation of China(82073898,82130101,82072276,and 82070083)Major Scientific And Technological Projects of Guangdong Province(2023B1111050008m,China)+1 种基金Science and Technology Innovation Project of Guangdong Provincial Drug Administration(2022ZDZ08,China)China Postdoctoral Science Foundation(2023M741601).
文摘To the Editor:Despite advancements in combinational antiretroviral treatment for HIV-1,cognitive impairments are still experienced by over 50%of acquired immunodeficiency syndrome patients1.Unlike other classical forms of neurologic dementia such as Alzheimer’s disease,HIV-associated neurocognitive disorder(HAND)predominantly manifests in younger individuals with HIV infection,which is categorized into asymptomatic neurocognitive impairment,mild neurocognitive disorder,and severe HIV-associated dementia,necessitating urgent development of effective diagnosis and treatment.
文摘As part of China's "the Belt and Road"strategy, China Railway Express provides alternative shipping routes and transportation modes from Asia to Europe and creates new opportunities for intermodal transportation in the shipping industry. A time–distancebased cost(time cost) function was proposed to compare China Railway Express with traditional transportation modes. Time cost was related to different types of cargoes,which exhibit distinct sensitivity to time. Using the proposed cost function as basis, we identified the cost indifference area where total costs are equal. Further analysis was performed for selecting the transportation mode and supply area for a specific cargo. This study provides various parties, such as business owners, the government, and the shipping industry, with many valuable insights.
