Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and...Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.展开更多
Summary What is already known about this topic?The active ingredient of the SA58 Nasal Spray is a broad-spectrum neutralizing antibody with a high neutralizing capacity against different Omicron subvariants in vitro s...Summary What is already known about this topic?The active ingredient of the SA58 Nasal Spray is a broad-spectrum neutralizing antibody with a high neutralizing capacity against different Omicron subvariants in vitro studies.What is added by this report?This study demonstrated the safety and effectiveness of SA58 Nasal Spray against coronavirus disease 2019(COVID-19)infection in medical personnel for the first time.What are the implications for public health practice?This study provides an effective approach for the public to reduce their risk of COVID-19 infection.The findings of this research have the potential to significantly reduce the risk of infection and limit human-to-human transmission in the event of a COVID-19 outbreak.展开更多
Microglia,the primary resident immune cells in the central nervous system(CNS),continuously survey the microenvironment via their ramified and motile processes to maintain brain homeostasis[1].As immune sentinels,micr...Microglia,the primary resident immune cells in the central nervous system(CNS),continuously survey the microenvironment via their ramified and motile processes to maintain brain homeostasis[1].As immune sentinels,microglia detect exogenous pathogens,elicit inflammation,promote tissue repair,and engage in the onset and progression of brain diseases[1].展开更多
Summary What is already known about this topic?Neutralization levels induced by inactivated vaccines rapidly wane after primary immunization,and a homologous booster can recall specific immune memory,resulting in a re...Summary What is already known about this topic?Neutralization levels induced by inactivated vaccines rapidly wane after primary immunization,and a homologous booster can recall specific immune memory,resulting in a remarkable increase in antibody concentration.The optimal interval between primary and booster doses has yet to be determined.展开更多
Microglia,the brain’s"busy bees",continuously survey the microenvironment by extending and retracting their ramified processes to maintain brain homeostasis[1,2].Upon disease or injury,microglia quickly tra...Microglia,the brain’s"busy bees",continuously survey the microenvironment by extending and retracting their ramified processes to maintain brain homeostasis[1,2].Upon disease or injury,microglia quickly transform their morphology and extend their processes towards the disease/injury sites to clear damage[2].The mechanisms underlying the high motility of microglial processes and the rapid morphological transformation of microglia have been extensively investigated.展开更多
Introduction:Repeat positive severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)following COVID-19 initial viral clearance(repositivity)poses a public health management challenge.The objective was to determine...Introduction:Repeat positive severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)following COVID-19 initial viral clearance(repositivity)poses a public health management challenge.The objective was to determine factors associated with neutralizing antibody(Nab)level and re-positivity among patients infected with a single strain SARS-CoV-2.Methods:During a single strain SARS-CoV-2 cluster in Beijing,China,longitudinal individual clinical,virological,and immunological data were collected from 368 infections from June 13 to September 22,2020.Factors associated with Nab level and re-positivity were analyzed using generalized estimating equations.Results:A total of 353(96%)SARS-CoV-2 infections had demographic,clinical,and laboratory data available.Among the 353 infections,55(15.5%)were re-positive,and blood draws were taken from 346 individuals(98.0%)during hospitalization and/or during the follow-up period.Symptoms were milder for the second-time admission for the re-positives,although 36.4%of re-positives presented with radiographic appearance of pneumonia manifestation.Compared to non-re-positive patients,NAb titers were lower among re-positives;NAb was positively associated with clinical severity.Samples from the lower respiratory tract manifested higher viral load than that from the upper respiratory tract.Multivariable analysis showed re-positivity was positively associated with being female[odd ratio(OR)=1.7,95%confidence interval(CI)1.1–2.8]and being aged<18 years(OR=5.2,95%CI 1.5–18.1);having initially asymptomatic infection(OR=13.7,95%CI 1.6–116.3);and negatively associated with a higher NAb level(OR=0.9,95%CI 0.5–1.7).Conclusions:NAb may be important for sustained viral clearance.Lower respiratory tract infection was associated with higher viral load among all infections when compared to upper respiratory tract infection.Continuous lower respiratory and intermittent upper respiratory viral shedding among COVID-19 infections may occur.展开更多
The concept of a mononuclear phagocyte system in which tissue-resident macrophages arise from the circulating monocytes has been dogma in immunology for more than half a century[1].While monocytes do give rise to macr...The concept of a mononuclear phagocyte system in which tissue-resident macrophages arise from the circulating monocytes has been dogma in immunology for more than half a century[1].While monocytes do give rise to macrophages under certain conditions,recent studies clearly dem on strate that monocytes do not primarily contribute to most adult tissue-resident macrophage pools under the steady state[2].Instead,the majority of adult tissue-resident macrophages are derived from erythromyeloid progenitors(EMPs)in the yolk sac that seed tissue before birth[2].展开更多
Few reports are available about prolonged shedding of coronavirus disease(COVID-19)virus,also known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),by immunocompetent patients.We report a case of an inf...Few reports are available about prolonged shedding of coronavirus disease(COVID-19)virus,also known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),by immunocompetent patients.We report a case of an infected,immunocompetent person with 169 days of COVID-19 virus shedding during which time he had two brief periods when he tested negative for COVID-19 followed by again testing positive.We describe relevant clinical,immunological,and genomic features.We found that continuous and prolonged viral replication and infectivity existed in an immunocompetent COVID-19 patient,despite having high neutralizing antibody titers.展开更多
基金supported by the Strategic Priority Research Program (XDB29010000)National Key Research and Development Program (2018YFA0900801)+5 种基金National Science Foundation Grants 32200135 and 12034006supported by National Science Fund for Distinguished Young Scholar (No.32325004)the NSFS Innovative Research Group (No.81921005)supported by the Young Elite Scientists Sponsorship Program by CAST (2022QNRC001)the Youth Innovation Promotion Association of CAS grantsupported by the Special Research Assistant Project of the Chinese Academy of Sciences.
文摘Varicella-zoster is a highly communicable virus that can be transmitted through the airborne route.About one quarter of people are infected with this virus.Previous studies have described the structure of A-capsid and a blurred reconstruction of the C-capsid with icosahedral symmetry.In this study,we have determined the more precise detailed structures of the varicella-zoster virus(VZV)B-and C-capsid in icosahedral symmetry using a combination of block-based reconstruction and symmetry relaxation strategies.In addition,we are reporting structural details of the portal vertex reconstructions in five-fold symmetry and portal reconstructions in twelve-fold symmetry.The structures unveil the basis for the high thermal stability of the VZV capsid.The conformational flexibility of structural elements of the capsid plays a role in the assembly of the capsid and drives processes critical for the viral life cycle.The results of the study open up new avenues for the development of drugs against a highly prevalent and contagious pathogen.
文摘Summary What is already known about this topic?The active ingredient of the SA58 Nasal Spray is a broad-spectrum neutralizing antibody with a high neutralizing capacity against different Omicron subvariants in vitro studies.What is added by this report?This study demonstrated the safety and effectiveness of SA58 Nasal Spray against coronavirus disease 2019(COVID-19)infection in medical personnel for the first time.What are the implications for public health practice?This study provides an effective approach for the public to reduce their risk of COVID-19 infection.The findings of this research have the potential to significantly reduce the risk of infection and limit human-to-human transmission in the event of a COVID-19 outbreak.
基金supported by the National Key Research and Development Program of China(2017YFA0104200)the National Natural Science Foundation of China(82090033)+1 种基金Leading Talents in Scientific and Technological Innovation in Zhejiang Province(2021R52021)a China Postdoctoral Science Foundation grant(2020M671693).
文摘Microglia,the primary resident immune cells in the central nervous system(CNS),continuously survey the microenvironment via their ramified and motile processes to maintain brain homeostasis[1].As immune sentinels,microglia detect exogenous pathogens,elicit inflammation,promote tissue repair,and engage in the onset and progression of brain diseases[1].
文摘Summary What is already known about this topic?Neutralization levels induced by inactivated vaccines rapidly wane after primary immunization,and a homologous booster can recall specific immune memory,resulting in a remarkable increase in antibody concentration.The optimal interval between primary and booster doses has yet to be determined.
基金supported by the National Natural Science Foundation of China(31671057)the Fundamental Research Funds for the Central Universities(2019FZA7009)。
文摘Microglia,the brain’s"busy bees",continuously survey the microenvironment by extending and retracting their ramified processes to maintain brain homeostasis[1,2].Upon disease or injury,microglia quickly transform their morphology and extend their processes towards the disease/injury sites to clear damage[2].The mechanisms underlying the high motility of microglial processes and the rapid morphological transformation of microglia have been extensively investigated.
基金This work was supported by the National Key Research and Development Program of China(2020YFA0707600)the National Key Research and Development Program of China(2020YFC0840800)+1 种基金Beijing Talent Project(2020A50)National Key R&D Program of China(2021ZD0114103).
文摘Introduction:Repeat positive severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)following COVID-19 initial viral clearance(repositivity)poses a public health management challenge.The objective was to determine factors associated with neutralizing antibody(Nab)level and re-positivity among patients infected with a single strain SARS-CoV-2.Methods:During a single strain SARS-CoV-2 cluster in Beijing,China,longitudinal individual clinical,virological,and immunological data were collected from 368 infections from June 13 to September 22,2020.Factors associated with Nab level and re-positivity were analyzed using generalized estimating equations.Results:A total of 353(96%)SARS-CoV-2 infections had demographic,clinical,and laboratory data available.Among the 353 infections,55(15.5%)were re-positive,and blood draws were taken from 346 individuals(98.0%)during hospitalization and/or during the follow-up period.Symptoms were milder for the second-time admission for the re-positives,although 36.4%of re-positives presented with radiographic appearance of pneumonia manifestation.Compared to non-re-positive patients,NAb titers were lower among re-positives;NAb was positively associated with clinical severity.Samples from the lower respiratory tract manifested higher viral load than that from the upper respiratory tract.Multivariable analysis showed re-positivity was positively associated with being female[odd ratio(OR)=1.7,95%confidence interval(CI)1.1–2.8]and being aged<18 years(OR=5.2,95%CI 1.5–18.1);having initially asymptomatic infection(OR=13.7,95%CI 1.6–116.3);and negatively associated with a higher NAb level(OR=0.9,95%CI 0.5–1.7).Conclusions:NAb may be important for sustained viral clearance.Lower respiratory tract infection was associated with higher viral load among all infections when compared to upper respiratory tract infection.Continuous lower respiratory and intermittent upper respiratory viral shedding among COVID-19 infections may occur.
基金This research highlight was supported by the National Natural Science Foundation of China(31671057)the Fundamental Research Funds for Central Universities,China(2019FZA7009).
文摘The concept of a mononuclear phagocyte system in which tissue-resident macrophages arise from the circulating monocytes has been dogma in immunology for more than half a century[1].While monocytes do give rise to macrophages under certain conditions,recent studies clearly dem on strate that monocytes do not primarily contribute to most adult tissue-resident macrophage pools under the steady state[2].Instead,the majority of adult tissue-resident macrophages are derived from erythromyeloid progenitors(EMPs)in the yolk sac that seed tissue before birth[2].
基金The National Key Research and Development Program of China(2020YFA0707600)the Scientific Research Project of Youan Hospital,CCMU,2020(BJYAYY-2020YC-01)the National Key Research and Development Program of China(2020YFC0840800).
文摘Few reports are available about prolonged shedding of coronavirus disease(COVID-19)virus,also known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),by immunocompetent patients.We report a case of an infected,immunocompetent person with 169 days of COVID-19 virus shedding during which time he had two brief periods when he tested negative for COVID-19 followed by again testing positive.We describe relevant clinical,immunological,and genomic features.We found that continuous and prolonged viral replication and infectivity existed in an immunocompetent COVID-19 patient,despite having high neutralizing antibody titers.
