Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)...Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.展开更多
The representation of the Arctic stratospheric circulation and the quasi-biennial oscillation(QBO)during the period 1981–2019 in a 40-yr Chinese global reanalysis dataset(CRA-40)is evaluated by comparing two widely u...The representation of the Arctic stratospheric circulation and the quasi-biennial oscillation(QBO)during the period 1981–2019 in a 40-yr Chinese global reanalysis dataset(CRA-40)is evaluated by comparing two widely used reanalysis datasets,ERA-5 and MERRA-2.CRA-40 demonstrates a comparable performance with ERA-5 and MERRA-2 in characterizing the winter and spring circulation in the lower and middle Arctic stratosphere.Specifically,differences in the climatological polar-mean temperature and polar night jet among the three reanalyses are within±0.5 K and±0.5 m s^(–1),respectively.The onset dates of the stratospheric sudden warming and stratospheric final warming events at 10 hPa in CRA-40,together with the dynamics and circulation anomalies during the onset process of warming events,are nearly identical to the other two reanalyses with slight differences.By contrast,the CRA-40 dataset demonstrates a deteriorated performance in describing the QBO below 10 hPa compared to the other two reanalysis products,manifested by the larger easterly biases of the QBO index,the remarkably weaker amplitude of the QBO,and the weaker wavelet power of the QBO period.Such pronounced biases are mainly concentrated in the period 1981–98 and largely reduced by at least 39%in 1999–2019.Thus,particular caution is needed in studying the QBO based on CRA-40.All three reanalyses exhibit greater disagreement in the upper stratosphere compared to the lower and middle stratosphere for both the polar region and the tropics.展开更多
This study uses multiple sea surface temperature （SST） datasets to perform a parallel comparison of three super El Nifios and their effects on the stratosphere. The results show that, different from ordinary El Nifi...This study uses multiple sea surface temperature （SST） datasets to perform a parallel comparison of three super El Nifios and their effects on the stratosphere. The results show that, different from ordinary El Nifios, warm SST anomalies appear earliest in the western tropical Pacific and precede the super El Nifio peak by more than 18 months. In the previous winter, relative to the mature phase of El Nifio, as a precursor, North Pacific Oscillation-like circulation anomalies are observed. A Pacific-North America （PNA） teleconnection appears in the extratropical troposphere during the mature phase, in spite of the subtle differences between the intensities, as well as the zonal position, of the PNA lobes. Related to the negative rainfall response over the tropical Indian Ocean, the PNA teleconnection in the winter of 1997/98 is the strongest among the three super El Nifios. The northern winter stratosphere shows large anomalies in the polar cap temperature and the circumpolar westerly, if the interferences from other factors are linearly filtered from the circulation data. Associated with the positive PNA response in a super El Nino winter, positive polar cap temperature anomalies and circumpolar easterly anomalies, though different in timing, are also observed in the mature winters of the three super El Nifios. The stratospheric polar vortex in the next winter relative to the 1982/83 and 1997/98 events is also anomalously weaker and warmer, and the stratospheric circulation conditions remain to be seen in the coming winter following the mature phase of the 2015/16 event.展开更多
This study focuses on model predictive skill with respect to stratospheric sudden warming(SSW) events by comparing the hindcast results of BCC_CSM1.1(m) with those of the ECMWF's model under the sub-seasonal to se...This study focuses on model predictive skill with respect to stratospheric sudden warming(SSW) events by comparing the hindcast results of BCC_CSM1.1(m) with those of the ECMWF's model under the sub-seasonal to seasonal prediction project of the World Weather Research Program and World Climate Research Program. When the hindcasts are initiated less than two weeks before SSW onset, BCC_CSM and ECMWF show comparable predictive skill in terms of the temporal evolution of the stratospheric circumpolar westerlies and polar temperature up to 30 days after SSW onset. However, with earlier hindcast initialization, the predictive skill of BCC_CSM gradually decreases, and the reproduced maximum circulation anomalies in the hindcasts initiated four weeks before SSW onset replicate only 10% of the circulation anomaly intensities in observations. The earliest successful prediction of the breakdown of the stratospheric polar vortex accompanying SSW onset for BCC_CSM(ECMWF) is the hindcast initiated two(three) weeks earlier. The predictive skills of both models during SSW winters are always higher than that during non-SSW winters, in relation to the successfully captured tropospheric precursors and the associated upward propagation of planetary waves by the model initializations. To narrow the gap in SSW predictive skill between BCC_CSM and ECMWF, ensemble forecasts and error corrections are performed with BCC_CSM. The SSW predictive skill in the ensemble hindcasts and the error corrections are improved compared with the previous control forecasts.展开更多
Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We compre...Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Beattie and Bresnahan locomotor rating scale scores,the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles(allogeneic:SMD=2.54,95% CI:2.05-3.02,P=0.0116,I2=65.5%;xenogeneic:SMD:1.78,95%CI:1.1-2.45,P=0.0116,I2=74.6%).Mesenchymal stem cellde rived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultra centrifugation(SMD=3.58,95% CI:2.62-4.53,P <0.0001,I2=31%) may be more effective than other EV isolation methods.For mouse Basso Mouse Scale scores,placenta-derived mesenchymal stem cell-de rived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles(placenta:SMD=5.25,95% CI:2.45-8.06,P=0.0421,I2=0%;bone marrow:SMD=1.82,95% CI:1.23-2.41,P=0.0421,I2=0%).For modified Neurological Severity Score,bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs(bone marrow:SMD=-4.86,95% CI:-6.66 to-3.06,P=0.0306,I2=81%;adipose:SMD=-2.37,95% CI:-3.73 to-1.01,P=0.0306,I2=0%).Intravenous administration(SMD=-5.47,95% CI:-6.98 to-3.97,P=0.0002,I2=53.3%) and dose of administration equal to 100 μg(SMD=-5.47,95% CI:-6.98 to-3.97,P <0.0001,I2=53.3%)showed better res ults than other administration routes and doses.The heterogeneity of studies was small,and sensitivity analysis also indicated stable results.Last,the methodological quality of all trials was mostly satisfactory.In conclusion,in the treatment of traumatic central nervous system diseases,mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.展开更多
Using the World Meteorological Organization definition and a threshold-based classification technique,simulations of vortex displacement and split sudden stratospheric warmings(SSWs)are evaluated for four Chinese mode...Using the World Meteorological Organization definition and a threshold-based classification technique,simulations of vortex displacement and split sudden stratospheric warmings(SSWs)are evaluated for four Chinese models(BCC-CSM2-MR,FGOALS-f3-L,FGOALS-g3,and NESM3)from phase 6 of the Coupled Model Intercomparison Project(CMIP6)with the Japanese 55-year reanalysis(JRA-55)as a baseline.Compared with six or seven SSWs in a decade in JRA-55,three models underestimate the SSW frequency by~50%,while NESM3 doubles the SSW frequency.SSWs mainly appear in midwinter in JRA-55,but one-month climate drift is simulated in the models.The composite of splits is stronger than displacements in both the reanalysis and most models due to the longer pulse of positive eddy heat flux before onset of split SSWs.A wavenumber-1-like temperature anomaly pattern(cold Eurasia,warm North America)before onset of displacement SSWs is simulated,but cold anomalies are mainly confined to North America after displacement SSWs.Although the lower tropospheric temperature also displays a wavenumber-1-like pattern before split SSWs,most parts of Eurasia and North America are covered by cold anomalies after split SSWs in JRA-55.The models have different degrees of fidelity for the temperature anomaly pattern before split SSWs,but the wavenumber-2-like temperature anomaly pattern is well simulated after split SSWs.The center of the negative height anomalies in the Pacific sector before SSWs is sensitive to the SSW type in both JRA-55 and the models.A negative North Atlantic Oscillation is simulated after both types of SSWs in the models,although it is only observed for split SSWs.展开更多
It is still not well understood if subseasonal variability of the local PM_(2.5) in the Beijing-Tianjin-Hebei(BTH)region is affected by the stratospheric state.Using PM_(2.5) observations and the ERA5 reanalysis,the e...It is still not well understood if subseasonal variability of the local PM_(2.5) in the Beijing-Tianjin-Hebei(BTH)region is affected by the stratospheric state.Using PM_(2.5) observations and the ERA5 reanalysis,the evolution of the air quality in BTH during the January 2021 sudden stratospheric warming(SSW)is explored.The subseasonal variability of the PM_(2.5) concentration after the SSW onset is evidently enhanced.Stratospheric circumpolar easterly anomalies lasted for 53 days during the January-February 2021 SSW with two evident stratospheric pulses arriving at the ground.During the tropospheric wave weakening period and the intermittent period of dormant stratospheric pulses,the East Asian winter monsoon weakened,anomalous temperature inversion developed in the lower troposphere,anomalous surface southerlies prevailed,atmospheric moisture increased,and the boundary layer top height lowered,all of which favor the accumulation of pollutant particulates,leading to two periods of pollution processes in the BTH region.In the phase of strengthened East Asian winter monsoon around the very beginning of the SSW and another two periods when stratospheric pulses had reached the near surface,opposite-signed circulation patterns and meteorological conditions were observed,which helped to dilute and diffuse air pollutants in the BTH region.As a result,the air quality was excellent during the two periods when the stratospheric pulse had reached the near surface.The increased subseasonal variation of the regional pollutant particulates after the SSW onset highlights the important role of the stratosphere in the regional environment and provides implications for the environmental prediction.展开更多
This study compares the climatology and long-term trend of northern winter stratospheric residual mean meridional circulation(RMMC), as well as its responses to El Ni?o-Southern Oscillation(ENSO), stratospheric Quasi ...This study compares the climatology and long-term trend of northern winter stratospheric residual mean meridional circulation(RMMC), as well as its responses to El Ni?o-Southern Oscillation(ENSO), stratospheric Quasi Biennial Oscillation(QBO), and solar cycle in ten reanalyses and a stratosphere-resolving model, CESM1-WACCM. The RMMC is a large-scale meridional circulation cell in the stratosphere, usually referred to as the estimate of the Brewer Dobson circulation(BDC). The distribution of the BDC is generally consistent among multiple reanalyses except that the NOAA twentieth century reanalysis(20RC) largely underestimates it. Most reanalyses(except ERA40 and ERA-Interim) show a strengthening trend for the BDC during 1979–2010. All reanalyses and CESM1-WACCM consistently reveal that the deep branch of the BDC is significantly enhanced in El Ni?o winters as more waves from the troposphere dissipate in the stratospheric polar vortex region. A secondary circulation cell is coupled to the temperature anomalies below the QBO easterly center at 50 hPa with tropical upwelling/cooling and midlatitude downwelling/warming, and similar secondary circulation cells also appear between 50–10 hPa and above 10 hPa to balance the temperature anomalies. The direct BDC response to QBO in the upper stratosphere creates a barrier near 30°N to prevent waves from propagating to midlatitudes, contributing to the weakening of the polar vortex. The shallow branch of the BDC in the lower stratosphere is intensified during solar minima, and the downwelling warms the Arctic lower stratosphere. The stratospheric responses to QBO and solar cycle in most reanalyses are generally consistent except in the two 20 CRs.展开更多
The tropospheric impact of Arctic ozone loss events is still debatable.In this study we investigate that question,using the ERA5 reanalysis and long-term integration by a climate-chemistry coupled model(CESM2-WACCM).W...The tropospheric impact of Arctic ozone loss events is still debatable.In this study we investigate that question,using the ERA5 reanalysis and long-term integration by a climate-chemistry coupled model(CESM2-WACCM).We begin with the frequency of Arctic ozone loss events.On average,such events occur once in early spring every 14−15 years in ERA5 data and in the model,both of which estimate that roughly 40%of the strong polar vortex events in March are coupled with Arctic ozone loss,the remaining 60%being uncoupled.The composite difference between the two samples might be attributed to the pure impact of the Arctic ozone loss-that is,to ozone loss alone,without the concurrent impact of strong polar vortices.Arctic ozone loss is accompanied by an increase in total ozone in midlatitudes,with the maximum centered in the Central North Pacific.Contrasting Arctic ozone loss events with pure strong polar vortex events that are uncoupled with ozone loss,observations confirm that the stratospheric Northern Annular Mode reverses earlier for the former.For pure strong vortex events in early spring(without Arctic ozone loss),the cold anomalies can extend from the stratosphere to the middle troposphere;when such events are strong,the near surface warm anomalies are biased toward the continents.In contrast,during the other 40%of strong early-spring polar vortex events,those coupled with ozone loss,a concurrent and delayed warming of the near surface over the Arctic and its neighboring areas is observed,due to vertical redistribution of solar radiation by the change in the ozone.展开更多
[Objectives] To identify ITS2 barcode of Lablab Semen Album and its adulterants,and provide a new method for the identification of Lablab Semen Album. [Methods] The ITS2 sequence was amplified by PCR and sequenced bi-...[Objectives] To identify ITS2 barcode of Lablab Semen Album and its adulterants,and provide a new method for the identification of Lablab Semen Album. [Methods] The ITS2 sequence was amplified by PCR and sequenced bi-directionally. After splicing by Codon Code Aligner,the data were processed with the aid MEGA software to construct the cluster dendrogram( neighbor-joining,NJ tree). [Results]The ITS2 sequence of Lablab Semen Album had length of 218 bp; the constructed cluster dendrogram indicated that all species were monophyletic and could be distinguished from other species. [Conclusions] The ITS2 barcode can be used for rapid identification of Lablab Semen Album and its adulterants and this experiment further verified that DNA barcode technology is effective in identification of traditional Chinese medicines.展开更多
Previous studies have reported a close relationship between the negative Arctic Oscillation(AO)and the PM_(2.5)(particulate matter with a diameter of 2.5μm or less)diffusion in North China in winter.Using the North C...Previous studies have reported a close relationship between the negative Arctic Oscillation(AO)and the PM_(2.5)(particulate matter with a diameter of 2.5μm or less)diffusion in North China in winter.Using the North China regional mean meridional wind at 850 hPa derived from the ERA5(ECMWF Reanalysis version 5)reanalysis data in 1979–2022 as a useful substitute for station observed PM_(2.5) concentration(since the latter is available only since 2014),our study detected strong/weak northerly events representing the abnormal PM_(2.5) diffusion/accumulation events,and revisited the AO–PM_(2.5) diffusion relationship in North China during 1979–2022.The results show that only when the AO was characterized by a 2-month continuously negative/positive phases and with twin peaks respectively before and after the diffusion/accumulation events,would there be higher occurrences of the abnormal PM_(2.5) diffusion/accumulation.The second peak of negative AO acted to prolong the strong northerly winds by an average of 2 days.Further analysis reveals that the AO with twin peaks always has a footprint in the stratospheric northern annular mode(NAM)during the abnormal PM_(2.5) events,and the coupling between the stratosphere and troposphere plays a critical role in the second peak of AO.Vertical propagation of baroclinically amplifying waves leads to changes in isentropic meridional mass fluxes in the stratosphere following the changes in the troposphere.The stronger/weaker poleward mass fluxes increase/decrease the polar mass in the stratosphere,which dominates the total column air mass changes and leads to the second peak of AO.Considering the subseasonal predictability of the stratospheric NAM based on existing evidence,particular attention should be paid to these AO-related abnormal PM_(2.5) diffusion and accumulation events in North China because they might be more predictable at a longer lead time.展开更多
This paper evaluates a representation of winter stratospheric circulation in the Antarctic that is based on CRA-40, a 40-year global reanalysis dataset released by the China Meteorological Administration, and compares...This paper evaluates a representation of winter stratospheric circulation in the Antarctic that is based on CRA-40, a 40-year global reanalysis dataset released by the China Meteorological Administration, and compares it with representations based on two other state-of-the-art reanalysis datasets: the fifth-generation atmospheric reanalysis provided by the European Centre for Medium-Range Weather Forecasts(ERA-5) and the Modern-Era Retrospective analysis for Research and Applications, version 2(MERRA-2). In terms of climatology, we find that CRA-40 portrays a stronger and colder polar vortex in the middle and lower stratosphere than ERA-5, but a weaker and warmer one than MERRA-2. However, disagreement among the three reanalyses is confined mainly to the period before1999, and is largely reduced after that time. On the interannual timescale, portrayals of the intensity and area of the 10-hPa polar vortex are quite consistent among the three reanalyses, with correlation coefficients greater than 0.9 between each pair of reanalyses. In addition, the central dates of most sudden stratospheric deceleration(SSD) events at 10 hPa in the three reanalyses differ by less than one day, indicating that CRA-40 is also highly consistent with the other two reanalysis datasets regarding daily evolution. Our analyses suggest that CRA-40 performs comparably to ERA-5 and MERRA-2 in characterizing winter circulation in the Antarctic middle and lower stratosphere.展开更多
This study compares two rainstorms that swept through Henan Province of China in July 2021 and August 1975.The heavy rainfall and related synoptic systems and processes are diagnosed based on hourly ERA5 reanalysis da...This study compares two rainstorms that swept through Henan Province of China in July 2021 and August 1975.The heavy rainfall and related synoptic systems and processes are diagnosed based on hourly ERA5 reanalysis data and precipitation observations from the China Meteorological Administration.It is estimated that most of the daily rainfall in Henan was caused by synoptic-scale precipitation,with the sub-synoptic convective rainfall intermittently dominating some of the hourly total rainfall.The rainband moved at about 2 m s^(-1) during the July 2021 rainstorm,whereas it was almost stationary during the August 1975 rainstorm when the heavy rainfall was concentrated in southern Henan.A double-typhoon circulation pattern with a subtropical high over the Bohai and Yellow Seas was observed during both rainstorms.The heavy rainfall during the July 2021 event was controlled remotely by Typhoons Cempaka and In-Fa,which provided a path for the transport of moisture via the southerly jet associated with Typhoon Cempaka and the easterly(or southeasterly)jet associated with Typhoon In-Fa.The rainstorm in August1975 was caused more directly by Typhoon Nina,which made landfall in Fujian Province and moved toward Henan Province.The rainfall around the inverted trough of the motionless Typhoon Nina produced a cumulative effect.The two rainstorms also differed in their circulation patterns in the upper troposphere.The intrusion of high potential vorticity air over Central China occurred in the July 2021 extreme rainstorm,whereas the South Asian high was enhanced and biased further north during the August 1975 rainstorm.Further analysis showed that the northward and westward transport of moisture took place during the July 2021 rainstorm,whereas the westward transport of moisture from the east of Henan dominated near the inverted trough of Typhoon Nina during the August 1975 rainstorm.展开更多
Many factors have been identified as having the ability to affect the sensitivity of rapid antigen detection(RAD)tests for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).This study aimed to identify the i...Many factors have been identified as having the ability to affect the sensitivity of rapid antigen detection(RAD)tests for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).This study aimed to identify the impact of sample processing on the sensitivity of the RAD tests.We explored the effect of different inactivation methods,viral transport media(VTM)solutions,and sample preservation on the sensitivity of four RAD kits based on two SARS-CoV-2 strains.Compared with non-inactivation,heat inactivation significantly impacted the sensitivity of most RAD kits;however,β-propiolactone inactivation only had a minor effect.Some of the VTM solutions(VTM2,MANTACC)had a significant influence on the sensitivity of the RAD kits,especially for low viral-loads samples.The detection value of RAD kits was slightly decreased,while most of them were still in the detection range with the extension of preservation time and the increase of freeze–thaw cycles.Our results showed that selecting the appropriate inactivation methods and VTM solutions is necessary during reagent development,performance evaluation,and clinical application。展开更多
The global coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a positive-sense RNA virus.How the host immune system senses and responds to SARS-CoV-2 inf...The global coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a positive-sense RNA virus.How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved.Here,we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway.SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation.cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection.We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion.Furthermore,cytoplasmic chromatin-cGAS-STING pathway,but not MAVS-mediated viral RNA sensing pathway,contributes to interferon and pro-inflammatory gene expression upon cell fusion.Finally,we show that cGAS is required for host antiviral responses against SARS-CoV-2,and a STING-activating compound potently inhibits viral replication.Together,our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection,mediated by cytoplasmic chromatin from the infected cells.Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19.In addition,these findings extend our knowledge in host defense against viral infection by showing that host cells’self-nucleic acids can be employed as a“danger signal”to alarm the immune system.展开更多
基金supported by the Fujian Minimally Invasive Medical Center Foundation,No.2128100514(to CC,CW,HX)the Natural Science Foundation of Fujian Province,No.2023J01640(to CC,CW,ZL,HX)。
文摘Spinal cord injury is a disabling condition with limited treatment options.Multiple studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord injury.Strikingly,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic potency.We thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord repair.SEVs or HSEVs were isolated from bone marrow MSC supernatants by density gradient ultracentrifugation.HSEV administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord inflammation.HSEVs regulate macrophage polarization towards the M2 phenotype in vivo and in vitro.Micro RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase 1.Reducing mi R-146a-5p expression in HSEVs partially attenuated macrophage polarization.Our data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage polarization.This study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41975048, 42030605, and 42175069)the Natural Science Foundation of Jiangsu Province (Grant No.BK20191404)
文摘The representation of the Arctic stratospheric circulation and the quasi-biennial oscillation(QBO)during the period 1981–2019 in a 40-yr Chinese global reanalysis dataset(CRA-40)is evaluated by comparing two widely used reanalysis datasets,ERA-5 and MERRA-2.CRA-40 demonstrates a comparable performance with ERA-5 and MERRA-2 in characterizing the winter and spring circulation in the lower and middle Arctic stratosphere.Specifically,differences in the climatological polar-mean temperature and polar night jet among the three reanalyses are within±0.5 K and±0.5 m s^(–1),respectively.The onset dates of the stratospheric sudden warming and stratospheric final warming events at 10 hPa in CRA-40,together with the dynamics and circulation anomalies during the onset process of warming events,are nearly identical to the other two reanalyses with slight differences.By contrast,the CRA-40 dataset demonstrates a deteriorated performance in describing the QBO below 10 hPa compared to the other two reanalysis products,manifested by the larger easterly biases of the QBO index,the remarkably weaker amplitude of the QBO,and the weaker wavelet power of the QBO period.Such pronounced biases are mainly concentrated in the period 1981–98 and largely reduced by at least 39%in 1999–2019.Thus,particular caution is needed in studying the QBO based on CRA-40.All three reanalyses exhibit greater disagreement in the upper stratosphere compared to the lower and middle stratosphere for both the polar region and the tropics.
基金supported by the Startup Foundation for Introducing Talent of Nanjing University of Information Science and Technology (Grant No. 2016r060)the National Key Research and Development Program (Grant No. 2016YFA0602104)+2 种基金the National Natural Science Foundation of China (Grant Nos. 41575041, 41430533 and 91437105)the Chinese Academy of Sciences (Grant No. XDA11010402)the China Meteorological Administration Special Public Welfare Research Fund (Grant No. GYHY201406001)
文摘This study uses multiple sea surface temperature （SST） datasets to perform a parallel comparison of three super El Nifios and their effects on the stratosphere. The results show that, different from ordinary El Nifios, warm SST anomalies appear earliest in the western tropical Pacific and precede the super El Nifio peak by more than 18 months. In the previous winter, relative to the mature phase of El Nifio, as a precursor, North Pacific Oscillation-like circulation anomalies are observed. A Pacific-North America （PNA） teleconnection appears in the extratropical troposphere during the mature phase, in spite of the subtle differences between the intensities, as well as the zonal position, of the PNA lobes. Related to the negative rainfall response over the tropical Indian Ocean, the PNA teleconnection in the winter of 1997/98 is the strongest among the three super El Nifios. The northern winter stratosphere shows large anomalies in the polar cap temperature and the circumpolar westerly, if the interferences from other factors are linearly filtered from the circulation data. Associated with the positive PNA response in a super El Nino winter, positive polar cap temperature anomalies and circumpolar easterly anomalies, though different in timing, are also observed in the mature winters of the three super El Nifios. The stratospheric polar vortex in the next winter relative to the 1982/83 and 1997/98 events is also anomalously weaker and warmer, and the stratospheric circulation conditions remain to be seen in the coming winter following the mature phase of the 2015/16 event.
基金supported by the National Key R&D Program of China (Grant Nos. 2016YFA0602104 and 2016YFA0602102)the National Natural Science Foundation of China (Grant Nos. 41705024, 41575041, 41705039 and 41705076)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDA17010105)the Startup Foundation for Introducing Talent of NUIST (Grant No. 2016r060)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘This study focuses on model predictive skill with respect to stratospheric sudden warming(SSW) events by comparing the hindcast results of BCC_CSM1.1(m) with those of the ECMWF's model under the sub-seasonal to seasonal prediction project of the World Weather Research Program and World Climate Research Program. When the hindcasts are initiated less than two weeks before SSW onset, BCC_CSM and ECMWF show comparable predictive skill in terms of the temporal evolution of the stratospheric circumpolar westerlies and polar temperature up to 30 days after SSW onset. However, with earlier hindcast initialization, the predictive skill of BCC_CSM gradually decreases, and the reproduced maximum circulation anomalies in the hindcasts initiated four weeks before SSW onset replicate only 10% of the circulation anomaly intensities in observations. The earliest successful prediction of the breakdown of the stratospheric polar vortex accompanying SSW onset for BCC_CSM(ECMWF) is the hindcast initiated two(three) weeks earlier. The predictive skills of both models during SSW winters are always higher than that during non-SSW winters, in relation to the successfully captured tropospheric precursors and the associated upward propagation of planetary waves by the model initializations. To narrow the gap in SSW predictive skill between BCC_CSM and ECMWF, ensemble forecasts and error corrections are performed with BCC_CSM. The SSW predictive skill in the ensemble hindcasts and the error corrections are improved compared with the previous control forecasts.
文摘Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Beattie and Bresnahan locomotor rating scale scores,the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles(allogeneic:SMD=2.54,95% CI:2.05-3.02,P=0.0116,I2=65.5%;xenogeneic:SMD:1.78,95%CI:1.1-2.45,P=0.0116,I2=74.6%).Mesenchymal stem cellde rived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultra centrifugation(SMD=3.58,95% CI:2.62-4.53,P <0.0001,I2=31%) may be more effective than other EV isolation methods.For mouse Basso Mouse Scale scores,placenta-derived mesenchymal stem cell-de rived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles(placenta:SMD=5.25,95% CI:2.45-8.06,P=0.0421,I2=0%;bone marrow:SMD=1.82,95% CI:1.23-2.41,P=0.0421,I2=0%).For modified Neurological Severity Score,bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs(bone marrow:SMD=-4.86,95% CI:-6.66 to-3.06,P=0.0306,I2=81%;adipose:SMD=-2.37,95% CI:-3.73 to-1.01,P=0.0306,I2=0%).Intravenous administration(SMD=-5.47,95% CI:-6.98 to-3.97,P=0.0002,I2=53.3%) and dose of administration equal to 100 μg(SMD=-5.47,95% CI:-6.98 to-3.97,P <0.0001,I2=53.3%)showed better res ults than other administration routes and doses.The heterogeneity of studies was small,and sensitivity analysis also indicated stable results.Last,the methodological quality of all trials was mostly satisfactory.In conclusion,in the treatment of traumatic central nervous system diseases,mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA17010105)the National Key R&D Program of China(Grant No.2016YFA0602104).
文摘Using the World Meteorological Organization definition and a threshold-based classification technique,simulations of vortex displacement and split sudden stratospheric warmings(SSWs)are evaluated for four Chinese models(BCC-CSM2-MR,FGOALS-f3-L,FGOALS-g3,and NESM3)from phase 6 of the Coupled Model Intercomparison Project(CMIP6)with the Japanese 55-year reanalysis(JRA-55)as a baseline.Compared with six or seven SSWs in a decade in JRA-55,three models underestimate the SSW frequency by~50%,while NESM3 doubles the SSW frequency.SSWs mainly appear in midwinter in JRA-55,but one-month climate drift is simulated in the models.The composite of splits is stronger than displacements in both the reanalysis and most models due to the longer pulse of positive eddy heat flux before onset of split SSWs.A wavenumber-1-like temperature anomaly pattern(cold Eurasia,warm North America)before onset of displacement SSWs is simulated,but cold anomalies are mainly confined to North America after displacement SSWs.Although the lower tropospheric temperature also displays a wavenumber-1-like pattern before split SSWs,most parts of Eurasia and North America are covered by cold anomalies after split SSWs in JRA-55.The models have different degrees of fidelity for the temperature anomaly pattern before split SSWs,but the wavenumber-2-like temperature anomaly pattern is well simulated after split SSWs.The center of the negative height anomalies in the Pacific sector before SSWs is sensitive to the SSW type in both JRA-55 and the models.A negative North Atlantic Oscillation is simulated after both types of SSWs in the models,although it is only observed for split SSWs.
基金supported by the National Natural Science Foundation of China(Grant Nos.42088101 and 42175069)the National Key R&D Program of China(Grant No.2018YFC1505602).
文摘It is still not well understood if subseasonal variability of the local PM_(2.5) in the Beijing-Tianjin-Hebei(BTH)region is affected by the stratospheric state.Using PM_(2.5) observations and the ERA5 reanalysis,the evolution of the air quality in BTH during the January 2021 sudden stratospheric warming(SSW)is explored.The subseasonal variability of the PM_(2.5) concentration after the SSW onset is evidently enhanced.Stratospheric circumpolar easterly anomalies lasted for 53 days during the January-February 2021 SSW with two evident stratospheric pulses arriving at the ground.During the tropospheric wave weakening period and the intermittent period of dormant stratospheric pulses,the East Asian winter monsoon weakened,anomalous temperature inversion developed in the lower troposphere,anomalous surface southerlies prevailed,atmospheric moisture increased,and the boundary layer top height lowered,all of which favor the accumulation of pollutant particulates,leading to two periods of pollution processes in the BTH region.In the phase of strengthened East Asian winter monsoon around the very beginning of the SSW and another two periods when stratospheric pulses had reached the near surface,opposite-signed circulation patterns and meteorological conditions were observed,which helped to dilute and diffuse air pollutants in the BTH region.As a result,the air quality was excellent during the two periods when the stratospheric pulse had reached the near surface.The increased subseasonal variation of the regional pollutant particulates after the SSW onset highlights the important role of the stratosphere in the regional environment and provides implications for the environmental prediction.
基金supported by grants from the National Natural Science Foundation of China(41705024,41875048)the National Key R&D Program of China(2016YFA0602104)+1 种基金the Planning and Budgeting Committee of the Council for Higher Education in Israelthe Startup Foundation for Introducing Talent of NUIST(2016r060)
文摘This study compares the climatology and long-term trend of northern winter stratospheric residual mean meridional circulation(RMMC), as well as its responses to El Ni?o-Southern Oscillation(ENSO), stratospheric Quasi Biennial Oscillation(QBO), and solar cycle in ten reanalyses and a stratosphere-resolving model, CESM1-WACCM. The RMMC is a large-scale meridional circulation cell in the stratosphere, usually referred to as the estimate of the Brewer Dobson circulation(BDC). The distribution of the BDC is generally consistent among multiple reanalyses except that the NOAA twentieth century reanalysis(20RC) largely underestimates it. Most reanalyses(except ERA40 and ERA-Interim) show a strengthening trend for the BDC during 1979–2010. All reanalyses and CESM1-WACCM consistently reveal that the deep branch of the BDC is significantly enhanced in El Ni?o winters as more waves from the troposphere dissipate in the stratospheric polar vortex region. A secondary circulation cell is coupled to the temperature anomalies below the QBO easterly center at 50 hPa with tropical upwelling/cooling and midlatitude downwelling/warming, and similar secondary circulation cells also appear between 50–10 hPa and above 10 hPa to balance the temperature anomalies. The direct BDC response to QBO in the upper stratosphere creates a barrier near 30°N to prevent waves from propagating to midlatitudes, contributing to the weakening of the polar vortex. The shallow branch of the BDC in the lower stratosphere is intensified during solar minima, and the downwelling warms the Arctic lower stratosphere. The stratospheric responses to QBO and solar cycle in most reanalyses are generally consistent except in the two 20 CRs.
基金supported by the National Natural Science Foundation of China(Grant NO.91837311).
文摘The tropospheric impact of Arctic ozone loss events is still debatable.In this study we investigate that question,using the ERA5 reanalysis and long-term integration by a climate-chemistry coupled model(CESM2-WACCM).We begin with the frequency of Arctic ozone loss events.On average,such events occur once in early spring every 14−15 years in ERA5 data and in the model,both of which estimate that roughly 40%of the strong polar vortex events in March are coupled with Arctic ozone loss,the remaining 60%being uncoupled.The composite difference between the two samples might be attributed to the pure impact of the Arctic ozone loss-that is,to ozone loss alone,without the concurrent impact of strong polar vortices.Arctic ozone loss is accompanied by an increase in total ozone in midlatitudes,with the maximum centered in the Central North Pacific.Contrasting Arctic ozone loss events with pure strong polar vortex events that are uncoupled with ozone loss,observations confirm that the stratospheric Northern Annular Mode reverses earlier for the former.For pure strong vortex events in early spring(without Arctic ozone loss),the cold anomalies can extend from the stratosphere to the middle troposphere;when such events are strong,the near surface warm anomalies are biased toward the continents.In contrast,during the other 40%of strong early-spring polar vortex events,those coupled with ozone loss,a concurrent and delayed warming of the near surface over the Arctic and its neighboring areas is observed,due to vertical redistribution of solar radiation by the change in the ozone.
基金Supported by Key Program for Sci-tech Plan of Hunan Province Science and Technology Department(2014SK2001)Sci-tech Project for Food and Drug Safety of Hunan Food and Drug Administration(Xiang Shi Yao Ke R201612)
文摘[Objectives] To identify ITS2 barcode of Lablab Semen Album and its adulterants,and provide a new method for the identification of Lablab Semen Album. [Methods] The ITS2 sequence was amplified by PCR and sequenced bi-directionally. After splicing by Codon Code Aligner,the data were processed with the aid MEGA software to construct the cluster dendrogram( neighbor-joining,NJ tree). [Results]The ITS2 sequence of Lablab Semen Album had length of 218 bp; the constructed cluster dendrogram indicated that all species were monophyletic and could be distinguished from other species. [Conclusions] The ITS2 barcode can be used for rapid identification of Lablab Semen Album and its adulterants and this experiment further verified that DNA barcode technology is effective in identification of traditional Chinese medicines.
基金Supported by the National Natural Science Foundation of China(42375060)Creative Research Group Fund of the National Natural Science Foundation of China(42021004)Natural Science Foundation of Jiangsu Province of China(BK20211288)。
文摘Previous studies have reported a close relationship between the negative Arctic Oscillation(AO)and the PM_(2.5)(particulate matter with a diameter of 2.5μm or less)diffusion in North China in winter.Using the North China regional mean meridional wind at 850 hPa derived from the ERA5(ECMWF Reanalysis version 5)reanalysis data in 1979–2022 as a useful substitute for station observed PM_(2.5) concentration(since the latter is available only since 2014),our study detected strong/weak northerly events representing the abnormal PM_(2.5) diffusion/accumulation events,and revisited the AO–PM_(2.5) diffusion relationship in North China during 1979–2022.The results show that only when the AO was characterized by a 2-month continuously negative/positive phases and with twin peaks respectively before and after the diffusion/accumulation events,would there be higher occurrences of the abnormal PM_(2.5) diffusion/accumulation.The second peak of negative AO acted to prolong the strong northerly winds by an average of 2 days.Further analysis reveals that the AO with twin peaks always has a footprint in the stratospheric northern annular mode(NAM)during the abnormal PM_(2.5) events,and the coupling between the stratosphere and troposphere plays a critical role in the second peak of AO.Vertical propagation of baroclinically amplifying waves leads to changes in isentropic meridional mass fluxes in the stratosphere following the changes in the troposphere.The stronger/weaker poleward mass fluxes increase/decrease the polar mass in the stratosphere,which dominates the total column air mass changes and leads to the second peak of AO.Considering the subseasonal predictability of the stratospheric NAM based on existing evidence,particular attention should be paid to these AO-related abnormal PM_(2.5) diffusion and accumulation events in North China because they might be more predictable at a longer lead time.
基金jointly supported by the NSFC project (42088101, 41975048, 42361144843, 42175069)。
文摘This paper evaluates a representation of winter stratospheric circulation in the Antarctic that is based on CRA-40, a 40-year global reanalysis dataset released by the China Meteorological Administration, and compares it with representations based on two other state-of-the-art reanalysis datasets: the fifth-generation atmospheric reanalysis provided by the European Centre for Medium-Range Weather Forecasts(ERA-5) and the Modern-Era Retrospective analysis for Research and Applications, version 2(MERRA-2). In terms of climatology, we find that CRA-40 portrays a stronger and colder polar vortex in the middle and lower stratosphere than ERA-5, but a weaker and warmer one than MERRA-2. However, disagreement among the three reanalyses is confined mainly to the period before1999, and is largely reduced after that time. On the interannual timescale, portrayals of the intensity and area of the 10-hPa polar vortex are quite consistent among the three reanalyses, with correlation coefficients greater than 0.9 between each pair of reanalyses. In addition, the central dates of most sudden stratospheric deceleration(SSD) events at 10 hPa in the three reanalyses differ by less than one day, indicating that CRA-40 is also highly consistent with the other two reanalysis datasets regarding daily evolution. Our analyses suggest that CRA-40 performs comparably to ERA-5 and MERRA-2 in characterizing winter circulation in the Antarctic middle and lower stratosphere.
基金Supported by the National Key Research and Development Program of China (2021YFC3000903)National Natural Science Foundation of China (42030605)。
文摘This study compares two rainstorms that swept through Henan Province of China in July 2021 and August 1975.The heavy rainfall and related synoptic systems and processes are diagnosed based on hourly ERA5 reanalysis data and precipitation observations from the China Meteorological Administration.It is estimated that most of the daily rainfall in Henan was caused by synoptic-scale precipitation,with the sub-synoptic convective rainfall intermittently dominating some of the hourly total rainfall.The rainband moved at about 2 m s^(-1) during the July 2021 rainstorm,whereas it was almost stationary during the August 1975 rainstorm when the heavy rainfall was concentrated in southern Henan.A double-typhoon circulation pattern with a subtropical high over the Bohai and Yellow Seas was observed during both rainstorms.The heavy rainfall during the July 2021 event was controlled remotely by Typhoons Cempaka and In-Fa,which provided a path for the transport of moisture via the southerly jet associated with Typhoon Cempaka and the easterly(or southeasterly)jet associated with Typhoon In-Fa.The rainstorm in August1975 was caused more directly by Typhoon Nina,which made landfall in Fujian Province and moved toward Henan Province.The rainfall around the inverted trough of the motionless Typhoon Nina produced a cumulative effect.The two rainstorms also differed in their circulation patterns in the upper troposphere.The intrusion of high potential vorticity air over Central China occurred in the July 2021 extreme rainstorm,whereas the South Asian high was enhanced and biased further north during the August 1975 rainstorm.Further analysis showed that the northward and westward transport of moisture took place during the July 2021 rainstorm,whereas the westward transport of moisture from the east of Henan dominated near the inverted trough of Typhoon Nina during the August 1975 rainstorm.
基金supported by China's National Science and Technology Major Project(2018ZX10102001)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT3100292020PT310004).
文摘Many factors have been identified as having the ability to affect the sensitivity of rapid antigen detection(RAD)tests for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).This study aimed to identify the impact of sample processing on the sensitivity of the RAD tests.We explored the effect of different inactivation methods,viral transport media(VTM)solutions,and sample preservation on the sensitivity of four RAD kits based on two SARS-CoV-2 strains.Compared with non-inactivation,heat inactivation significantly impacted the sensitivity of most RAD kits;however,β-propiolactone inactivation only had a minor effect.Some of the VTM solutions(VTM2,MANTACC)had a significant influence on the sensitivity of the RAD kits,especially for low viral-loads samples.The detection value of RAD kits was slightly decreased,while most of them were still in the detection range with the extension of preservation time and the increase of freeze–thaw cycles.Our results showed that selecting the appropriate inactivation methods and VTM solutions is necessary during reagent development,performance evaluation,and clinical application。
基金This work was supported by grants from National Key R&D Program of China(2020YFA0707600 to Z.Z.,2020YFA0707800 to W.Wei.)the National Natural Science Foundation of China(81930063,31870893,and 81971948 to J.W.,Z.Z.,and X.L.)+3 种基金the National Major Sciences&Technology Project for Control and Prevention of Major Infectious Diseases in China(2018ZX10301401 to Z.Z.and X.L.)the Beijing Municipal Science&Technology Commission(Z181100001318009)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2016-I2M-1-014,2016-I2M-1-005 to J.W.and X.L.)the Beijing Advanced Innovation Center for Genomics(ICG)at Peking University,and the Peking-Tsinghua Center for Life Sciences.
文摘The global coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),a positive-sense RNA virus.How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved.Here,we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway.SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation.cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection.We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion.Furthermore,cytoplasmic chromatin-cGAS-STING pathway,but not MAVS-mediated viral RNA sensing pathway,contributes to interferon and pro-inflammatory gene expression upon cell fusion.Finally,we show that cGAS is required for host antiviral responses against SARS-CoV-2,and a STING-activating compound potently inhibits viral replication.Together,our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection,mediated by cytoplasmic chromatin from the infected cells.Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19.In addition,these findings extend our knowledge in host defense against viral infection by showing that host cells’self-nucleic acids can be employed as a“danger signal”to alarm the immune system.
