Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.展开更多
Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for t...Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in antiEbola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G(Ig G) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.展开更多
Dear Editor,Migrasomes are newly discovered cellular organelles with diameters of 0.5–3μm which have been found to be produced by normal and cancer cells,and distributed in various organs of animals(Ma et al.,2015)a...Dear Editor,Migrasomes are newly discovered cellular organelles with diameters of 0.5–3μm which have been found to be produced by normal and cancer cells,and distributed in various organs of animals(Ma et al.,2015)and in human sera(Zhao et al.,2019).Migrasomes are present inside the cavities of pulmonary alveoli,blood vessels and lymph capillaries(Zhang et al.,2020),and can be captured by surrounding cells with their cargoes internalized.展开更多
Land subsidence can be observed with time-series of Interferometric Synthetic Aperture Radar(InSAR)data.However,existing approaches only reveal subsidence signals that are multi-scale mixed,which is not conducive to t...Land subsidence can be observed with time-series of Interferometric Synthetic Aperture Radar(InSAR)data.However,existing approaches only reveal subsidence signals that are multi-scale mixed,which is not conducive to the systematic analysis of subsidence of different mechanisms.A deformation signal decomposition(DSD)method based on spectral analysis is used to decompose the deformation extracted by time-series InSAR into three classes of deformation signals.They refer to large-scale deformation related to geological settings,medium-scale deformation caused more by group excavation,and small-scale deformation along linear infrastructures.TerraSAR-X datasets for Shanghai spanning April 2013 to September 2020,and Sentinel-1A datasets spanning January 2016 to September 2020 are used in this study.The results were cross-verified between the TerraSAR-X and Sentinel-1A datasets,and validated against levelling measurements.Subsidence signals caused by different mechanisms were automatically decomposed,which facilitates a systematic analysis for targeted diagnosis of land subsidence signals.A detailed analysis was conducted jointly at three scales of surface displacement,geological conditions,major construction activities,and subsidence mechanisms.It indicated that construction activities were the leading cause of land subsidence,and suggests that local authorities that wish to mitigate surface subsidence may benefit from primarily considering this process.展开更多
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
基金supported by Important National Science & Technology Specific Projects (2012ZX10004403)
文摘Full-length nucleoproteins from Ebola and Marburg viruses were expressed as His-tagged recombinant proteins in Escherichia coli and nucleoprotein-based enzyme-linked immunosorbent assays(ELISAs) were established for the detection of antibodies specific to Ebola and Marburg viruses. The ELISAs were evaluated by testing antisera collected from rabbit immunized with Ebola and Marburg virus nucleoproteins. Although little cross-reactivity of antibodies was observed in antiEbola virus nucleoprotein rabbit antisera, the highest reactions to immunoglobulin G(Ig G) were uniformly detected against the nucleoprotein antigens of homologous viruses. We further evaluated the ELISA's ability to detect antibodies to Ebola and Marburg viruses using human sera samples collected from individuals passing through the Guangdong port of entry. With a threshold set at the mean plus three standard deviations of average optical densities of sera tested, the ELISA systems using these two recombinant nucleoproteins have good sensitivity and specificity. These results demonstrate the usefulness of ELISA for diagnostics as well as ecological and serosurvey studies of Ebola and Marburg virus infection.
基金supported by the National Natural Science Foundation of China (31970172 and 82171736)the National Key Research and Development Program of China (2022YFC2304300)。
文摘Dear Editor,Migrasomes are newly discovered cellular organelles with diameters of 0.5–3μm which have been found to be produced by normal and cancer cells,and distributed in various organs of animals(Ma et al.,2015)and in human sera(Zhao et al.,2019).Migrasomes are present inside the cavities of pulmonary alveoli,blood vessels and lymph capillaries(Zhang et al.,2020),and can be captured by surrounding cells with their cargoes internalized.
基金supported by the National Natural Science Foundation of China[grant number 42101450]the Open Fund of State Key Laboratory of Information Engineering in Surveying,Mapping and Remote Sensing,Wuhan University[grant number 21R03]the Comparative Study of Geo-environment and Geohazards in the Yangtze River Delta and the Red River Delta Project,the Shanghai Science and Technology Development Foundation[grant number 20dz1201200].
文摘Land subsidence can be observed with time-series of Interferometric Synthetic Aperture Radar(InSAR)data.However,existing approaches only reveal subsidence signals that are multi-scale mixed,which is not conducive to the systematic analysis of subsidence of different mechanisms.A deformation signal decomposition(DSD)method based on spectral analysis is used to decompose the deformation extracted by time-series InSAR into three classes of deformation signals.They refer to large-scale deformation related to geological settings,medium-scale deformation caused more by group excavation,and small-scale deformation along linear infrastructures.TerraSAR-X datasets for Shanghai spanning April 2013 to September 2020,and Sentinel-1A datasets spanning January 2016 to September 2020 are used in this study.The results were cross-verified between the TerraSAR-X and Sentinel-1A datasets,and validated against levelling measurements.Subsidence signals caused by different mechanisms were automatically decomposed,which facilitates a systematic analysis for targeted diagnosis of land subsidence signals.A detailed analysis was conducted jointly at three scales of surface displacement,geological conditions,major construction activities,and subsidence mechanisms.It indicated that construction activities were the leading cause of land subsidence,and suggests that local authorities that wish to mitigate surface subsidence may benefit from primarily considering this process.
