Architectural Computer-Aided Design(CAD)is a highly technical and practical course and is also a course where its knowledge can be directly applied in the working field,which is especially important for higher vocatio...Architectural Computer-Aided Design(CAD)is a highly technical and practical course and is also a course where its knowledge can be directly applied in the working field,which is especially important for higher vocational students majoring in architecture.In order to improve the teaching quality of this course,this paper proposes the integration of competition content into teaching under the based on the original syllabus.Therefore,the content of the“Reading and Drafting of Construction Drawings”competition is integrated into the teaching of this course,so as to realize the balanced development of teaching and competition,enhance students’professional skills and practical ability,and help students adapt to the development of the industry.With that,the goal of personnel training in higher vocational colleges can be achieved.展开更多
Architectural Computer-Aided Design(CAD)is a basic course for architectural engineering majors in vocational colleges.The integration of competition into teaching will not only help stimulate the students’enthusiasm,...Architectural Computer-Aided Design(CAD)is a basic course for architectural engineering majors in vocational colleges.The integration of competition into teaching will not only help stimulate the students’enthusiasm,but also help them improve their professional skills.However,there are still some problems in the teaching of Architectural CAD.Therefore,teachers must continuously optimize the integration of competition content into Architectural CAD classes through various strategies,so as to give full play to the value of competition content in classes.We explored and analyzed the problems in the integration of competition content into Architectural CAD classes,and proposed specific strategies,in hopes of improving the quality of Architectural CAD teaching.展开更多
抑郁症是最常见的精神疾病之一,其患病人群在不断增长.并且,抑郁症的终生患病率为15%~18%,即大约每5人中就有一个人在其一生中经历过抑郁发作.压力应激作为一种环境因素是抑郁症的主要成因之一.经历了压力应激却没有发展至抑郁症的人群...抑郁症是最常见的精神疾病之一,其患病人群在不断增长.并且,抑郁症的终生患病率为15%~18%,即大约每5人中就有一个人在其一生中经历过抑郁发作.压力应激作为一种环境因素是抑郁症的主要成因之一.经历了压力应激却没有发展至抑郁症的人群具有压力应激韧性(resilience).探索压力应激韧性的神经机制,对抑郁症在临床上预防和治疗将发挥至关重要的作用.本文主要关注压力应激韧性的神经机制的研究进展,首先简要介绍了压力应激韧性研究中常用的慢性社交挫败应激模型(chronic social defeat stress,CSDS),其次重点对压力应激韧性相关的大脑区域在分子、细胞和神经环路水平上的研究进展进行总结,接下来介绍压力应激韧性的临床前机制研究所带来的临床转化,最后讨论和展望压力应激韧性在未来的研究方向.展开更多
Pore size and distribution in carbon-based materials are regarded to be a key factor to affect the electrochemical capacitive performances of the resultant electrodes.In this study,nitrogen and oxygen codoped porous c...Pore size and distribution in carbon-based materials are regarded to be a key factor to affect the electrochemical capacitive performances of the resultant electrodes.In this study,nitrogen and oxygen codoped porous carbons(NOPCs) are fabricated based on a simple Schiff-base reaction between m-phenylenediamine and terephthalaldehyde.The NOPCs have tunable morphologies,high surface areas,abundant heteroatom doping.More importantly,the carbons show a dominant micropores of 0.5-0.8 nm,comparable to the ionic sizes of LiTFSI(Li^+0.069 nm;TFSI-0.79 nm) water-in-salt electrolyte with a high potential window of 2.2 V.Consequently,the fabricated symmetric supercapacitor gives a high energy output of 30.5 Wh/kg at 1 kW/kg,and high stability after successive 10,000 cycles with ^96.8% retention.This study provides promising potential to develop high-energy supercapacitors.展开更多
During the 20th century the global climate has been shifted towards warmer and drier regimes, mainly due to anthropogenic warming [1,2]. Climate changes can notably disrupt the environment and ecosystems. To evaluate ...During the 20th century the global climate has been shifted towards warmer and drier regimes, mainly due to anthropogenic warming [1,2]. Climate changes can notably disrupt the environment and ecosystems. To evaluate the impacts of climate change on ecoregions, the Kdppen-Trewartha (K-T) climate classification [3] is widely used because it was constructed on the basis of surface vegetation. The K-T classification system combines temperature, precipitation, and their seasonality into a single metric. Six major climate types and several sub-climate types are defined (A: tropical, B: dry, C: subtropical, D: temperate, E: subpolar, F: polar). Each K-T climate type is consistent with certain prevalent plant species. Definitions and criteria of K-T climate types were outlined by Feng et al.[4].展开更多
Coxsackievirus A10(CVA10)is one of the major etiological agents of hand,foot,and mouth disease.There are no vaccine and antiviral drugs for controlling CVA10 infection.Reverse genetic tools for CVA10 will benefit its ...Coxsackievirus A10(CVA10)is one of the major etiological agents of hand,foot,and mouth disease.There are no vaccine and antiviral drugs for controlling CVA10 infection.Reverse genetic tools for CVA10 will benefit its mechanistic study and development of vaccines and antivirals.Here,two infectious clones for the prototype and a Myc-tagged CVA10 were constructed.Viable CVA10 viruses were harvested by transfecting the viral m RNA into human rhabdomyosarcoma(RD)cells.Rescued CVA10 was further confirmed by next generation sequencing and characterized experimentally.We also constructed the vectors for CVA10 subgenomic replicon with luciferase reporter and viral capsid with EGFP reporter,respectively.Co-transfection of the viral replicon RNA and capsid expresser in human embryonic kidney 293 T(HEK293 T)cells led to the production of single round infectious particles(SRIPs).Based on CVA10 replicon RNA,SRIPs with either the enterovirus A71(EVA71)capsid or the CVA10 capsid were generated.Infection by EVA71 SRIPs required SCARB2,while CVA10 SRIPs did not.Finally,we showed great improvement of the replicon activity and SRIPs production by insertion of a cis-active hammerhead ribozyme(HHRib)before the 50-untranslated region(UTR).In summary,reverse genetic tools for prototype strain of CVA10,including both the infectious clone and the SRIPs system,were successfully established.These tools will facilitate the basic and translational study of CVA10.展开更多
Background and Aims:Hepatic sinusoidal obstruction syndrome(HSOS)is a life-threatening syndrome,and a cause is exposure to pyrrolizidine alkaloid(PA)-containing products.It is well-established that retrorsine(RTS),a r...Background and Aims:Hepatic sinusoidal obstruction syndrome(HSOS)is a life-threatening syndrome,and a cause is exposure to pyrrolizidine alkaloid(PA)-containing products.It is well-established that retrorsine(RTS),a rep-resentative Pas,insults hepatic sinusoidal endothelial cells and ensues congestion of hepatic sinusoids.However,little known about the impact of Pas on gut microbiota and intesti-nal barrier and inflammation in HSOS.Methods:Mice were gavaged with or without nonabsorbable antibiotics(ABX),followed by a single dose of RTS.The gut microbiota was examined by 16S rDNA sequencing.Results:ABX pretreat-ment significantly reversed RTS-induced liver damage.RTS altered gut microbiota composition,increasing Gram-nega-tive bacteria and resulting in a sharp elevation of circulating lipopolysaccharides(LPS)in HSOS mice.Gut decontamina-tion with ABX alleviated RTS-induced intestine inflamma-tion,protected against disruption of the intestinal epithelial barrier and gut vascular barrier(GVB),and suppressed he-patic LPS-NF-κB pathway activation in RTS-induced HSOS.Importantly,the LPS level was positively correlated with MELD score in patients with HSOS.Elevated LPS in patients with HSOS confirmed that Gram-negative bacteria were in-volved in the pathogenesis of HSOS.Conclusions:RTS,a PA,cooperated with gut dysbiosis to cause intestinal inflam-mation and gut barrier compromise that increased transport of gut-derived LPS into the liver through the portal vein,which contributed to the pathology of HSOS.Modulating the gut microbiota,protecting the intestinal barrier,and sup-pressing intestinal inflammation with prebiotics or antibiot-ics might be a useful pharmacologic intervention in HSOS.展开更多
Multi-photon-pumped lasing based on metal-halide perovskites is promising for nonlinear optics and practical frequency-upconversion devices in integrated photonic systems.However,at present almost all the multi-photon...Multi-photon-pumped lasing based on metal-halide perovskites is promising for nonlinear optics and practical frequency-upconversion devices in integrated photonic systems.However,at present almost all the multi-photon-pumped lasing emissions from perovskite microcavities were limited for two-photon excitation,and also suffered from a compromise in room temperature or low temperature operation conditions.In this study,based on the vapor-phase epitaxial CsPbBr3 microplatelets with high crystallinity,self-formed high-quality microcavities,and great thermal stability,low-threshold and high-quality factor whispering gallery mode lasing was realized under single-,two-,and three-photon excitation,and the lasing action is very stable under continuous pulsed laser irradiation(~3.6×10^(7) laser shots).More importantly,the three-photon-pumped lasing can be efficiently sustained at a high temperature of~400 K,and the characteristic temperature was determined to be as high as~152.6 K,indicating the highly temperature-insensitive gain threshold.Note that this is the first report on high-temperature three-photon-pumped lasing on perovskite microcavities.Moreover,an aggressive thermal cycling test(two cycles,290-400-290 K)was further performed to indicate the stability and repeatability of the multi-photon-pumped lasing characteristics.It can be anticipated that the results obtained represent a significant step toward the temperature-insensitive frequency-upconversion lasing,inspiring the exploitation of advantageous perovskites for novel applications.展开更多
Interleukin-37(IL-37)is an inhibitory member of the IL-1 family of cytokines.We previously found that balanced selection maintains common variations of the human IL37 gene.However,the functional consequences of this s...Interleukin-37(IL-37)is an inhibitory member of the IL-1 family of cytokines.We previously found that balanced selection maintains common variations of the human IL37 gene.However,the functional consequences of this selection have yet to be validated.Here,using cells expressing exogenous IL-37 variants,including IL-37 Ref and IL-37 Var1 and Var2,we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune stimulation.The protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1,despite the comparable mRNA levels of all three variants.Further study showed that IL-37 Var2 was rapidly degraded by a proteasome-dependent mechanism mediated by enhanced polyubiquitination,leading to a transient upregulation of IL-37 Var2 after immune stimulation.Finally,when ectopically expressed in cells,human IL-37 Var2 exerted less inhibition on proinflammatory cytokine production than did other IL-37 variants.Conversely,purified extracellular IL-37 variant proteins demonstrated comparable inhibitory abilities in vitro.In conclusion,our study reveals that common genetic variants of IL37 lead to different immune-inhibitory potencies,primarily as a result of differences in IL-37 protein stability,suggesting the possible involvement of these variants in various human diseases.展开更多
Human immunodeficiency virus type 1 (HIV-1) infection can damage humoral immunity. The knowledge of B cell perturbations during chronic HIV-1 infection and their recovery after combined antiretroviral therapy (cART...Human immunodeficiency virus type 1 (HIV-1) infection can damage humoral immunity. The knowledge of B cell perturbations during chronic HIV-1 infection and their recovery after combined antiretroviral therapy (cART) is not complete yet, and thus attempts to further improve humoral immunity are impeded. In this study, an HIV-1 chronically infected cohort with similar demographics, infection history, genetic background, and HIV-1 genotype was established to probe B cell perturbations. Results showed that the B cells from this cohort were highly activated and prone to cell death, and B cell compartments were altered significantly. Notably, although cART partially reversed the hyperactivation and reduced tissue-like memory B cells, other B cell perturbations, including impaired expression of survival factor Bcl-2, costimulatory molecules, and shrunken resting memory B cells, were irreversible. Further functional characterization revealed that the influenza HA- specific antibody-secreting cells were significantly lower during HIV-1 infection, whereas the recalled antibody response to HIV-l-specific antigens was decreased after cART. Finally, CpG plus R848 treatment increased the survival of B cells and memory B cells in vitro from HIV-l-infected patients. In conclusion, this study identified irreversible B cell immune perturbations in chronic HIV-1 infections regardless of cART and proposed the potential strategy to enhance B cell functions through the improvement of cell survival.展开更多
A facile fabrication strategy is reported to obtain N/O codoped porous carbon nanosheets for pur-pose of ameliorating the charge transfer and accumulation in the concentrated LiTFSI(lithium bis(trifluoromethane sulfon...A facile fabrication strategy is reported to obtain N/O codoped porous carbon nanosheets for pur-pose of ameliorating the charge transfer and accumulation in the concentrated LiTFSI(lithium bis(trifluoromethane sulfonyl)imide)electrolyte.By tunning the feed ratio of comonomers,the porous nanosheet structure is endowed with a significant ion-adsorption surface area(1630 m^(2)/g)and intercon-nected hierarchical porosity;meanwhile,high-level N/O dopants(N:3.58 at%,O:12.91 at%)increase the effective contact area for electrolyte ions,and further facilitate rapid ion/electron transfer.Benefiting from the advantageous features,carbon nanosheets electrode reveal an enhanced specific capacitance(375 F/g)in three-electrode configuration and the H_(2)SO_(4)-based device yields a high gravimetric energy density of 11.4 Wh/kg.Particularly,the ion-diffusion highways in porous carbon nanosheets contribute to the 2.25 V LiTFSI-based symmetric device with a high energy delivery up to 33.1 Wh/kg.This work offers an in-spiring strategy for facile fabrication of carbon nanosheets,and demonstrates their promising application in“water-in-salt”electrolyte-based supercapacitor systems.展开更多
The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications,enabling the development of effective therapeutic a...The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications,enabling the development of effective therapeutic and preventive strategies.In this study,our initial attempts to introduce a NanoLuc luciferase(NLuc)reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies.We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus.Therefore,we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71(EV-A71),coxsackievirus A10(CVA10),coxsackievirus A7(CVA7),coxsackievirus A16(CVA16),namely EV-A71-HiBiT,CVA16-HiBiT,CVA10-HiBiT,CVA7-HiBiT,and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency.Notably,the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses.A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics.Moreover,these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages.In addition,the HiBiT-tagged viruses were successfully tested in antiviral drug assays,and the sensitivity of the viruses to drugs was not affected by the HiBiT tag.Ultimately,our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal,convenient,and invaluable method for advancing research in the realm of enterovirus virology.Furthermore,HiBiT-tagged enteroviruses exhibit great potential for diverse applications,including the development of antivirals and the elucidation of viral infection mechanisms.展开更多
基金co-supported by the Guangdong Major Project of Basic and Applied Basic Research [grant number 2021B0301030007]the National Key Research and Development Program of China [grant number 2017YFA0604302]+1 种基金the National Natural Science Foundation of China [grant number 41875137]the National Key Scientific and Technological Infrastructure project"Earth System Science Numerical Simulator Facility"(EarthLab)
基金Research on Teaching Reform and Practice of Architectural CAD Course in Higher Vocational Colleges under the Mode of Integration of Competition and Teaching(Project number:GZ223279)。
文摘Architectural Computer-Aided Design(CAD)is a highly technical and practical course and is also a course where its knowledge can be directly applied in the working field,which is especially important for higher vocational students majoring in architecture.In order to improve the teaching quality of this course,this paper proposes the integration of competition content into teaching under the based on the original syllabus.Therefore,the content of the“Reading and Drafting of Construction Drawings”competition is integrated into the teaching of this course,so as to realize the balanced development of teaching and competition,enhance students’professional skills and practical ability,and help students adapt to the development of the industry.With that,the goal of personnel training in higher vocational colleges can be achieved.
基金Project Name:Research on Teaching Reform and Practice of Architectural CAD Course in Higher Vocational Colleges Under the Mode of“Integration of Competition and Teaching”(Project No.:GZ223279)。
文摘Architectural Computer-Aided Design(CAD)is a basic course for architectural engineering majors in vocational colleges.The integration of competition into teaching will not only help stimulate the students’enthusiasm,but also help them improve their professional skills.However,there are still some problems in the teaching of Architectural CAD.Therefore,teachers must continuously optimize the integration of competition content into Architectural CAD classes through various strategies,so as to give full play to the value of competition content in classes.We explored and analyzed the problems in the integration of competition content into Architectural CAD classes,and proposed specific strategies,in hopes of improving the quality of Architectural CAD teaching.
文摘抑郁症是最常见的精神疾病之一,其患病人群在不断增长.并且,抑郁症的终生患病率为15%~18%,即大约每5人中就有一个人在其一生中经历过抑郁发作.压力应激作为一种环境因素是抑郁症的主要成因之一.经历了压力应激却没有发展至抑郁症的人群具有压力应激韧性(resilience).探索压力应激韧性的神经机制,对抑郁症在临床上预防和治疗将发挥至关重要的作用.本文主要关注压力应激韧性的神经机制的研究进展,首先简要介绍了压力应激韧性研究中常用的慢性社交挫败应激模型(chronic social defeat stress,CSDS),其次重点对压力应激韧性相关的大脑区域在分子、细胞和神经环路水平上的研究进展进行总结,接下来介绍压力应激韧性的临床前机制研究所带来的临床转化,最后讨论和展望压力应激韧性在未来的研究方向.
基金financially supported by the National Natural Science Foundation of China(Nos.21875165,51772216 and 21703161)the Science and Technology Commission of Shanghai Municipality,China(No.14DZ2261100)the Fundamental Research Funds for the Central Universities。
文摘Pore size and distribution in carbon-based materials are regarded to be a key factor to affect the electrochemical capacitive performances of the resultant electrodes.In this study,nitrogen and oxygen codoped porous carbons(NOPCs) are fabricated based on a simple Schiff-base reaction between m-phenylenediamine and terephthalaldehyde.The NOPCs have tunable morphologies,high surface areas,abundant heteroatom doping.More importantly,the carbons show a dominant micropores of 0.5-0.8 nm,comparable to the ionic sizes of LiTFSI(Li^+0.069 nm;TFSI-0.79 nm) water-in-salt electrolyte with a high potential window of 2.2 V.Consequently,the fabricated symmetric supercapacitor gives a high energy output of 30.5 Wh/kg at 1 kW/kg,and high stability after successive 10,000 cycles with ^96.8% retention.This study provides promising potential to develop high-energy supercapacitors.
基金supported by the Central Asia Atmospheric Science Foundation(CAAS201701)the National Natural Science Foundation of China(41877446)the Fundamental Research Funds for the Central Universities(lzujbky-2018-140)
文摘During the 20th century the global climate has been shifted towards warmer and drier regimes, mainly due to anthropogenic warming [1,2]. Climate changes can notably disrupt the environment and ecosystems. To evaluate the impacts of climate change on ecoregions, the Kdppen-Trewartha (K-T) climate classification [3] is widely used because it was constructed on the basis of surface vegetation. The K-T classification system combines temperature, precipitation, and their seasonality into a single metric. Six major climate types and several sub-climate types are defined (A: tropical, B: dry, C: subtropical, D: temperate, E: subpolar, F: polar). Each K-T climate type is consistent with certain prevalent plant species. Definitions and criteria of K-T climate types were outlined by Feng et al.[4].
基金supported by the Shanghai Public Health Clinical Center(KY-GW2018-17)Shanghai Municipal Commission of Health and Family Planning(20174Y0099)。
文摘Coxsackievirus A10(CVA10)is one of the major etiological agents of hand,foot,and mouth disease.There are no vaccine and antiviral drugs for controlling CVA10 infection.Reverse genetic tools for CVA10 will benefit its mechanistic study and development of vaccines and antivirals.Here,two infectious clones for the prototype and a Myc-tagged CVA10 were constructed.Viable CVA10 viruses were harvested by transfecting the viral m RNA into human rhabdomyosarcoma(RD)cells.Rescued CVA10 was further confirmed by next generation sequencing and characterized experimentally.We also constructed the vectors for CVA10 subgenomic replicon with luciferase reporter and viral capsid with EGFP reporter,respectively.Co-transfection of the viral replicon RNA and capsid expresser in human embryonic kidney 293 T(HEK293 T)cells led to the production of single round infectious particles(SRIPs).Based on CVA10 replicon RNA,SRIPs with either the enterovirus A71(EVA71)capsid or the CVA10 capsid were generated.Infection by EVA71 SRIPs required SCARB2,while CVA10 SRIPs did not.Finally,we showed great improvement of the replicon activity and SRIPs production by insertion of a cis-active hammerhead ribozyme(HHRib)before the 50-untranslated region(UTR).In summary,reverse genetic tools for prototype strain of CVA10,including both the infectious clone and the SRIPs system,were successfully established.These tools will facilitate the basic and translational study of CVA10.
基金the National Natural Science Foundation of China(No.81974078,81570530,81370550 to LY,No.8190034336 to WW)Natural Science Founda-tion of Hubei Province(No.2019ACA133 to LY)。
文摘Background and Aims:Hepatic sinusoidal obstruction syndrome(HSOS)is a life-threatening syndrome,and a cause is exposure to pyrrolizidine alkaloid(PA)-containing products.It is well-established that retrorsine(RTS),a rep-resentative Pas,insults hepatic sinusoidal endothelial cells and ensues congestion of hepatic sinusoids.However,little known about the impact of Pas on gut microbiota and intesti-nal barrier and inflammation in HSOS.Methods:Mice were gavaged with or without nonabsorbable antibiotics(ABX),followed by a single dose of RTS.The gut microbiota was examined by 16S rDNA sequencing.Results:ABX pretreat-ment significantly reversed RTS-induced liver damage.RTS altered gut microbiota composition,increasing Gram-nega-tive bacteria and resulting in a sharp elevation of circulating lipopolysaccharides(LPS)in HSOS mice.Gut decontamina-tion with ABX alleviated RTS-induced intestine inflamma-tion,protected against disruption of the intestinal epithelial barrier and gut vascular barrier(GVB),and suppressed he-patic LPS-NF-κB pathway activation in RTS-induced HSOS.Importantly,the LPS level was positively correlated with MELD score in patients with HSOS.Elevated LPS in patients with HSOS confirmed that Gram-negative bacteria were in-volved in the pathogenesis of HSOS.Conclusions:RTS,a PA,cooperated with gut dysbiosis to cause intestinal inflam-mation and gut barrier compromise that increased transport of gut-derived LPS into the liver through the portal vein,which contributed to the pathology of HSOS.Modulating the gut microbiota,protecting the intestinal barrier,and sup-pressing intestinal inflammation with prebiotics or antibiot-ics might be a useful pharmacologic intervention in HSOS.
基金supported by the National Natural Science Foundation of China(Nos.11774318,12074347,61935009,and 12004346)the Open Fund of the State Key Laboratory of Integrated Optoelectronics(Nos.1OSKL2020KF04).
文摘Multi-photon-pumped lasing based on metal-halide perovskites is promising for nonlinear optics and practical frequency-upconversion devices in integrated photonic systems.However,at present almost all the multi-photon-pumped lasing emissions from perovskite microcavities were limited for two-photon excitation,and also suffered from a compromise in room temperature or low temperature operation conditions.In this study,based on the vapor-phase epitaxial CsPbBr3 microplatelets with high crystallinity,self-formed high-quality microcavities,and great thermal stability,low-threshold and high-quality factor whispering gallery mode lasing was realized under single-,two-,and three-photon excitation,and the lasing action is very stable under continuous pulsed laser irradiation(~3.6×10^(7) laser shots).More importantly,the three-photon-pumped lasing can be efficiently sustained at a high temperature of~400 K,and the characteristic temperature was determined to be as high as~152.6 K,indicating the highly temperature-insensitive gain threshold.Note that this is the first report on high-temperature three-photon-pumped lasing on perovskite microcavities.Moreover,an aggressive thermal cycling test(two cycles,290-400-290 K)was further performed to indicate the stability and repeatability of the multi-photon-pumped lasing characteristics.It can be anticipated that the results obtained represent a significant step toward the temperature-insensitive frequency-upconversion lasing,inspiring the exploitation of advantageous perovskites for novel applications.
基金supported by grants from the National Natural Science Foundation of China(No.81371823 to SZ and No.31500697 to JS)the 973 Project(No.2015CB554300 to SZ)the Shanghai Pujiang Program(No.15PJ1407300 to JS).
文摘Interleukin-37(IL-37)is an inhibitory member of the IL-1 family of cytokines.We previously found that balanced selection maintains common variations of the human IL37 gene.However,the functional consequences of this selection have yet to be validated.Here,using cells expressing exogenous IL-37 variants,including IL-37 Ref and IL-37 Var1 and Var2,we found that the three variants of IL-37 exhibited different immunoregulatory potencies in response to immune stimulation.The protein level of IL-37 Var2 was found to be significantly less than that of IL-37 Ref or Var1,despite the comparable mRNA levels of all three variants.Further study showed that IL-37 Var2 was rapidly degraded by a proteasome-dependent mechanism mediated by enhanced polyubiquitination,leading to a transient upregulation of IL-37 Var2 after immune stimulation.Finally,when ectopically expressed in cells,human IL-37 Var2 exerted less inhibition on proinflammatory cytokine production than did other IL-37 variants.Conversely,purified extracellular IL-37 variant proteins demonstrated comparable inhibitory abilities in vitro.In conclusion,our study reveals that common genetic variants of IL37 lead to different immune-inhibitory potencies,primarily as a result of differences in IL-37 protein stability,suggesting the possible involvement of these variants in various human diseases.
文摘Human immunodeficiency virus type 1 (HIV-1) infection can damage humoral immunity. The knowledge of B cell perturbations during chronic HIV-1 infection and their recovery after combined antiretroviral therapy (cART) is not complete yet, and thus attempts to further improve humoral immunity are impeded. In this study, an HIV-1 chronically infected cohort with similar demographics, infection history, genetic background, and HIV-1 genotype was established to probe B cell perturbations. Results showed that the B cells from this cohort were highly activated and prone to cell death, and B cell compartments were altered significantly. Notably, although cART partially reversed the hyperactivation and reduced tissue-like memory B cells, other B cell perturbations, including impaired expression of survival factor Bcl-2, costimulatory molecules, and shrunken resting memory B cells, were irreversible. Further functional characterization revealed that the influenza HA- specific antibody-secreting cells were significantly lower during HIV-1 infection, whereas the recalled antibody response to HIV-l-specific antigens was decreased after cART. Finally, CpG plus R848 treatment increased the survival of B cells and memory B cells in vitro from HIV-l-infected patients. In conclusion, this study identified irreversible B cell immune perturbations in chronic HIV-1 infections regardless of cART and proposed the potential strategy to enhance B cell functions through the improvement of cell survival.
基金financially supported by the National Natural Science Foundation of China (Nos. 21875165, 51772216, 22172111 and 21905207)the Science and Technology Commission of Shanghai Municipality, China (Nos. 20ZR1460300, 14DZ2261100)+2 种基金Anhui University of Science and Technology Introduced Talent Research Startup Fund (No. 13210572)Zhejiang Provincial Natural Science Foundation of China (No. LY19B010003)the Fundamental Research Funds for the Central Universities and the Large Equipment Test Foundation of Tongji University
文摘A facile fabrication strategy is reported to obtain N/O codoped porous carbon nanosheets for pur-pose of ameliorating the charge transfer and accumulation in the concentrated LiTFSI(lithium bis(trifluoromethane sulfonyl)imide)electrolyte.By tunning the feed ratio of comonomers,the porous nanosheet structure is endowed with a significant ion-adsorption surface area(1630 m^(2)/g)and intercon-nected hierarchical porosity;meanwhile,high-level N/O dopants(N:3.58 at%,O:12.91 at%)increase the effective contact area for electrolyte ions,and further facilitate rapid ion/electron transfer.Benefiting from the advantageous features,carbon nanosheets electrode reveal an enhanced specific capacitance(375 F/g)in three-electrode configuration and the H_(2)SO_(4)-based device yields a high gravimetric energy density of 11.4 Wh/kg.Particularly,the ion-diffusion highways in porous carbon nanosheets contribute to the 2.25 V LiTFSI-based symmetric device with a high energy delivery up to 33.1 Wh/kg.This work offers an in-spiring strategy for facile fabrication of carbon nanosheets,and demonstrates their promising application in“water-in-salt”electrolyte-based supercapacitor systems.
基金supported by the National Natural Science Foundation of China(grant nos.82002135 and 82172250).
文摘The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications,enabling the development of effective therapeutic and preventive strategies.In this study,our initial attempts to introduce a NanoLuc luciferase(NLuc)reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies.We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus.Therefore,we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71(EV-A71),coxsackievirus A10(CVA10),coxsackievirus A7(CVA7),coxsackievirus A16(CVA16),namely EV-A71-HiBiT,CVA16-HiBiT,CVA10-HiBiT,CVA7-HiBiT,and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency.Notably,the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses.A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics.Moreover,these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages.In addition,the HiBiT-tagged viruses were successfully tested in antiviral drug assays,and the sensitivity of the viruses to drugs was not affected by the HiBiT tag.Ultimately,our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal,convenient,and invaluable method for advancing research in the realm of enterovirus virology.Furthermore,HiBiT-tagged enteroviruses exhibit great potential for diverse applications,including the development of antivirals and the elucidation of viral infection mechanisms.