A novel structure of Ag gridlSiN_(x)/n+-c-Si/n-c-Si/i-a-Si:H/p^(+)-a-Si:HlTCO/Ag grid was designed to increase the ef-ficiency of bifacial amorphous/crystalline silicon-based solar cells and reduce the rear material c...A novel structure of Ag gridlSiN_(x)/n+-c-Si/n-c-Si/i-a-Si:H/p^(+)-a-Si:HlTCO/Ag grid was designed to increase the ef-ficiency of bifacial amorphous/crystalline silicon-based solar cells and reduce the rear material consumption and production cost.The simulation results show that the new structure obtains higher efficiency compared with the typical bifa-cial amorphous/crystalline silicon-based solar cell because of an increase in the short-circuit current(J_(sc)),while retaining the advantages of a high open-circuit voltage,low temperature coefficient,and good weak-light performance.Moreover,real cells composed of the novel structure with dimensions of 75 mm×75 mm were fabricated by a special fabrication recipe based on industrial processes.Without parameter optimization,the cell efficiency reached 21.1%with the J_(sc)of 41.7 mA/cm^(2).In addition,the novel structure attained 28.55%potential conversion efficiency under an illumination of AM 1.5 G,100 mW/cm^(2).We conclude that the configuration of the Ag grid/SiN_(x)/n^(+)-c-Si/n-c-Si/i-a-Si:H/p^(+)-a-Si:H/TCO/Ag grid is a promising structure for high efficiency and low cost.展开更多
This study demonstrates the yield asymmetry in Mg-3Al-1Zn alloy containing both ND-texture(c-axis//ND(Normal direction))and TD-texture(c-axis//TD(Transverse direction))in a quantitative view.The results showed that th...This study demonstrates the yield asymmetry in Mg-3Al-1Zn alloy containing both ND-texture(c-axis//ND(Normal direction))and TD-texture(c-axis//TD(Transverse direction))in a quantitative view.The results showed that the yield asymmetry is strongly dependent on the distribution of bimodal texture components,on the basis of the successful establishment of the quantified relationship between pre-deformation parameters and texture components distribution.It’s meaningful for providing key reference to texture design.Mechanical behavior of bimodal textured Mg alloy under tension and compression was tested.CYS/TYS(compressive yield stress/tensile yield stress)equal to 1 is obtained,implying that the yield asymmetry is eliminated when two textures distribute at specific fractions.The corresponding mechanism for the texture-dependence of tension-compression yield asymmetry is revealed by the analysis of slip/twinning activities and a compound use of the activation stress difference of slip/twinning(ΔStress)and geometrical compatibility factor(m′)between neighboring grains.Balanced activity of{10■2}twinning and a quite similar boundary obstacle effect against slip/twinning transfer under tension and compression accounts for such good symmetry performance.展开更多
In the face of multiple challenges brought by the changes of global climate and environment,developing clean energy and updating green energy storage equipment are important ways to achieve carbon peak and carbon neut...In the face of multiple challenges brought by the changes of global climate and environment,developing clean energy and updating green energy storage equipment are important ways to achieve carbon peak and carbon neutrality.Aqueous batteries have become a research hotspot due to their advantages of using the multivalent charge carrier,high ionic conductivity,environmental friendliness and cost effectiveness.In this work,the Cu_(2)Se@C(Cu_(2)Se coated on carbon clothes)thin film with a three-dimensional braided structure is fabricated by a simple electrochemical deposition method for Cu^(2+)storage for the first time.Compared with the commercial Cu_(2)Se powder,the well-designed Cu_(2)Se@C film shows enhanced specific capacity(640 mAh/g at 0.5 A/g)and rate performance(542 mAh/g at 5 A/g)as well as superior cycling stability(82.7%capacity retention after 1000 cycles at 1 A/g).The Cu^(2+)storage mechanism of the Cu_(2)Se@C electrode is based on a reversible phase transition process of Cu_(2)Se←→Cu_(2-x)Se←→CuSe←→CuSe_(2).In kinetic characteristic analysis,the Cu_(2)Se@C electrode demonstrates faster Cu^(2+)diffusion in discharge process than charge process resulting from the phase transition and the variation of interplanar spacing.This work highlights a facile one-piece design strategy and opens a new gateway for the exploration of advanced aqueous energy storage systems.展开更多
High-efficiency hydrogen production through photoelectrochemical(PEC)water splitting has emerged as a promising solution to address current global energy challenges.Ⅲ-nitride semiconductor photoelectrodes with nanost...High-efficiency hydrogen production through photoelectrochemical(PEC)water splitting has emerged as a promising solution to address current global energy challenges.Ⅲ-nitride semiconductor photoelectrodes with nanostructures have demonstrated great potential in the near future due to their high light absorption,tunable direct band gap,and strong physicochemical stability.However,several issues,including surface trapping centers,surface Fermi level pinning,and surface band bending,need to be addressed.In this work,enhanced photovoltaic properties have been achieved using gallium nitride(GaN)nanowires(NWs)photoelectrodes by adopting an alkaline solution surface treatment method to reduce the surface states.It was found that surface oxides on NWs can be removed by an alkaline solution treatment without changing the surface morphology through X-ray photoelectron spectroscopy(XPS),scanning electron microscopy(SEM)and other characterization methods.These findings provide new insights to the development of high-efficiency photoelectrodes for new energy source applications.展开更多
The investigation concentrates on friction stir welded(FSW)Al-Cu-Li alloy concerning its local microstructural evolution and mechanical properties.The grain features were characterized by electron back scattered diffr...The investigation concentrates on friction stir welded(FSW)Al-Cu-Li alloy concerning its local microstructural evolution and mechanical properties.The grain features were characterized by electron back scattered diffraction(EBSD)technology,while precipitate characterization was conducted by using transmission electron microscopy(TEM)aligned along[011]Al and[001]Al zone axes.The mechanical properties are evaluated through micro-hardness and tensile testing.It can be found that nugget zones exhibit finely equiaxed grains evolved through complete dynamic recrystallization(DRX),primarily occurring in continuous dynamic recrystallization(CDRX)and discontinuous dynamic recrystallization(DDRX).In the thermal-mechanically affected zone(TMAZ),numerous sub-structured grains,exhibiting an elongated morphology,were created due to partial DRX,signifying the dominance of CDRX,DDRX,and geometric dynamic recrystallization(GDRX)in this region.T_(1)completely dissolves in the nugget zone(NZ)leading to the formation of Guinier-Preston zones and increase ofδ′,β′and S′.Conversely,T_(1)partially solubilizes in TMAZ,the lowest hardness zone(LHZ)and heat affected zone(HAZ),and the residual T_(1)undergoes marked coarsening,revealing various T_(1)variants.The solubilization and coarsening of T_(1)are primary contributors to the degradation of hardness and strength.θ′primarily dissolves and coarsens in NZ and TMAZ,whilst this precipitate largely coarsens in HAZ and LHZ.σ,TB,grain boundary phases(GBPs)and precipitate-free zone(PFZ)are newly generated during FSW.σexists in the TMAZ,LHZ and HAZ,whereas TB nucleates in NZ.GBPs and PFZ mostly develop in LHZ and HAZ,which can cause strain localization during tensile deformation,potentially leading to LHZ joint fracture.展开更多
In 1957,Macfarlane Burnet proposed the theory that harnessing the body’s immune system could be an effective method for cancer treatment[1].Today,T-cell-based immunotherapies have indeed become a vital part of cancer...In 1957,Macfarlane Burnet proposed the theory that harnessing the body’s immune system could be an effective method for cancer treatment[1].Today,T-cell-based immunotherapies have indeed become a vital part of cancer treatment[2].However,a deeper understanding of antitumor immunity is still necessary to further support these treatments.Notably,CD4^(+)T cells are central to mediating antitumor immune responses[3,4,5,6],yet the cellular and molecular programs governing CD4^(+)T-cell antitumor immunity remain unclear.Our recent research revealed that CD4^(+)T-cell immunity is critically dependent on an intrinsic stem-like program[7].展开更多
T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains constrained.The objective of this study was to...T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains constrained.The objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor CD8^(+)T cells using the TRAMP-C1 prostate cancer and B16F10 melanoma model.To achieve this,we generated an Irf4^(GFP-DTR) mouse strain and discovered that CD8^(+)tumor-infiltrating lymphocytes(TILs)expressing high levels of IRF4.GFP exhibited a more differentiated PD-1high cell phenotype.By administering diphtheria toxin to tumor-bearing Irf4^(GFP-DTR) mice,we partially depleted IRF4.GFP^(+)TILs and observed an accelerated tumor growth.To specifically explore the function of IRF4 in antitumor CD8^(+)T cells,we conducted 3 adoptive cell therapy(ACT)models.Firstly,depleting IRF4.GFP^(+)CD8^(+)TILs derived from ACT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor progression.Secondly,deleting the Irf4 gene in antitumor CD8^(+)T cells used for ACT led to a reduction in the frequency and effector differentiation of CD8^(+)TILs,completely abolishing the antitumor effects of ACT.Lastly,we performed a temporal deletion of the Irf4 gene in antitumor CD8^(+)T cells during ACT,starting from 20 days after tumor implantation,which significantly compromised tumor control.Therefore,sustained expression of IRF4 is essential for maintaining CD8^(+)T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.展开更多
Sulfate radicals have been increasingly used for the pathogen inactivation due to their strong redox ability and high selectivity for electron-rich species in the last decade.The application of sulfate radicals in wat...Sulfate radicals have been increasingly used for the pathogen inactivation due to their strong redox ability and high selectivity for electron-rich species in the last decade.The application of sulfate radicals in water disinfection has become a very promising technology.However,there is currently a lack of reviews of sulfate radicals inactivated pathogenic microorganisms.At the same time,less attention has been paid to disinfection by-products produced by the use of sulfate radicals to inactivate microorganisms.This paper begins with a brief overview of sulfate radicals’properties.Then,the progress in water disinfection by sulfate radicals is summarized.The mechanism and inactivation kinetics of inactivating microorganisms are briefly described.After that,the disinfection by-products produced by reactions of sulfate radicals with chlorine,bromine,iodide ions and organic halogens in water are also discussed.In response to these possible challenges,this article concludes with some specific solutions and future research directions.展开更多
Congenital proximal radioulnar synostosis(CPRUS)is a rare anomaly which is caused by abnormal fusion of the proximal radius and ulna during development.This is due to the failure of embryological separation,resulting ...Congenital proximal radioulnar synostosis(CPRUS)is a rare anomaly which is caused by abnormal fusion of the proximal radius and ulna during development.This is due to the failure of embryological separation,resulting in the fixed position of the forearm,from mild to severe pronation.1Mild deformity leads to slight disability because the shoulder and wrist can effectively compensate.2 Patients with bilateral cases and/or pronation defor-mity of>60°may be severely limited in daily activities.34 Most surgeons recommend surgical intervention when the loss of forearm rotation exceeds 60°,particularly when the forearm is fixed in pronation.展开更多
Early-onset epilepsy is a neurological abnormality in childhood, and it is especially common in the first2 years after birth. Seizures in early life mostly result from structural or metabolic disorders in the brain, a...Early-onset epilepsy is a neurological abnormality in childhood, and it is especially common in the first2 years after birth. Seizures in early life mostly result from structural or metabolic disorders in the brain, and the genetic causes of idiopathic seizures have been extensively investigated. In this study, we identified four missense mutations in the SETD1 A gene(SET domain-containing 1 A, histone lysine methyltransferase): three de novo mutations in three individuals and one inherited mutation in a four-generation family. Whole-exome sequencing indicated that all four of these mutations were responsible for the seizures. Mutations of SETD1 A have been implicated in schizophrenia and developmental disorders, so we examined the role of the four mutations(R913 C, Q269 R, G1369 R, and R1392 H) in neural development. We found that their expression in mouse primary cortical neurons affected excitatory synapse development. Moreover, expression of the R913 C mutation also affected the migration of cortical neurons in the mouse brain.We further identified two common genes(Neurl4 and Usp39) affected by mutations of SETD1 A. These results suggested that the mutations of SETD1 A play a fundamental role in abnormal synaptic function and the development of neurons, so they may be pathogenic factors for neurodevelopmental disorders.展开更多
The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens.This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine...The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens.This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function.Herein,we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance.We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune tolerance,followed by discussing other cytokines that maintain immune tolerance through inducing CD_(4)^(+) Foxp_(3)^(+) regulatory T cells(Tregs),which negatively control immune cells.Interleukin(IL)-2 is the most potent cytokine in promoting the development and survival of Tregs,thereby mediating immune tolerance.IL-35 is mainly produced by Tregs,but its biology function remains to be defi ned.Finally,we discuss the actions of proinflammatory cytokines that breach immune tolerance and induce autoimmunity,which include IL-7,IL-12,IL-21,and IL-23.Recent genetic studies have revealed the role of these cytokines(or their cognate receptors)in susceptibility to autoimmune diseases.Taken together,we highlight in this review the cytokine regulation of immune tolerance,which will help in further understanding of human diseases that are caused by dysregulated immune system.展开更多
Embryo implantation and decidualization are crucial for successful pregnancy,which include multiple genes and signaling pathways,while the precise mechanism regarding embryo implantation and decidualization has yet to...Embryo implantation and decidualization are crucial for successful pregnancy,which include multiple genes and signaling pathways,while the precise mechanism regarding embryo implantation and decidualization has yet to be explored.The GABA which activates GABA_(A)or GABA_(B)receptors has been found playing an important role in early pregnancy.Here we seek to investigate whether GABA_(B)receptors participate in embryo implantation in mice.This study first characterized the spatiotemporal expression pattern of GABA_(B)receptors in the uterus during the peri-implantation period and found that GABA_(B1)expression was drastically upregulated in stromal cells on days 4e6,a period of embryo implantation and early stages of decidualization.Embryo delayed implantation and oil-induced decidualization models were further used to confirm that the GABA_(B1)was associated with embryo implantation and decidualization.We also found estrogen or progesterone had no directly effect on expression of GABA_(B1)in ovariectomized model.Because we were unable to detect significant GABA_(B2)which couples with GABA_(B1)to form whole GABA_(B)receptors,and the agonist and antagonist of whole GABA_(B)receptors had weak effect on the proliferation and differentiation of stromal cells as well,we excluded the possibility whole GABA_(B)receptors function,and concluded it should be non-classical signals of GABA_(B1)involving in embryo implantation and decidualization.Future studies should focus on investigating the roles and mechanisms of GABA_(B1)during embryo implantation and decidualization.展开更多
Understanding the molecular mechanisms of coronavirus disease 2019(COVID-19)pathogenesis and immune response is vital for developing therapies.Single-cell RNA sequencing has been applied to delineate the cellular hete...Understanding the molecular mechanisms of coronavirus disease 2019(COVID-19)pathogenesis and immune response is vital for developing therapies.Single-cell RNA sequencing has been applied to delineate the cellular heterogeneity of the host response toward COVID-19 in multiple tissues and organs.Here,we review the applications and findings from over 80 original COVID-19 single-cell RNA sequencing studies as well as many secondary analysis studies.We describe that single-cell RNA sequencing reveals multiple features of COVID-19 patients with different severity,including cell populations with proportional alteration,COVID-19-induced genes and pathways,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in single cells,and adaptation of immune repertoire.We also collect published single-cell RNA sequencing datasets from original studies.Finally,we discuss the limitations in current studies and perspectives for future advance.展开更多
基金Project supported by the Jiangxi Provincial Key Research and Development Foundation,China(Grant No.2016BBH80043)the Open Fund of Jiangsu Key Laboratory of Materials and Technology for Energy Conversion,China(Grant No.NJ20160032)the National Natural Science Foundation of China(Grant Nos.61741404,61464007,and 51561022)
文摘A novel structure of Ag gridlSiN_(x)/n+-c-Si/n-c-Si/i-a-Si:H/p^(+)-a-Si:HlTCO/Ag grid was designed to increase the ef-ficiency of bifacial amorphous/crystalline silicon-based solar cells and reduce the rear material consumption and production cost.The simulation results show that the new structure obtains higher efficiency compared with the typical bifa-cial amorphous/crystalline silicon-based solar cell because of an increase in the short-circuit current(J_(sc)),while retaining the advantages of a high open-circuit voltage,low temperature coefficient,and good weak-light performance.Moreover,real cells composed of the novel structure with dimensions of 75 mm×75 mm were fabricated by a special fabrication recipe based on industrial processes.Without parameter optimization,the cell efficiency reached 21.1%with the J_(sc)of 41.7 mA/cm^(2).In addition,the novel structure attained 28.55%potential conversion efficiency under an illumination of AM 1.5 G,100 mW/cm^(2).We conclude that the configuration of the Ag grid/SiN_(x)/n^(+)-c-Si/n-c-Si/i-a-Si:H/p^(+)-a-Si:H/TCO/Ag grid is a promising structure for high efficiency and low cost.
基金co-supported by National Natural Science Foundation of China(51901202,52101132)Natural Science Foundation of Jiangsu Province(No.BK 20191442)。
文摘This study demonstrates the yield asymmetry in Mg-3Al-1Zn alloy containing both ND-texture(c-axis//ND(Normal direction))and TD-texture(c-axis//TD(Transverse direction))in a quantitative view.The results showed that the yield asymmetry is strongly dependent on the distribution of bimodal texture components,on the basis of the successful establishment of the quantified relationship between pre-deformation parameters and texture components distribution.It’s meaningful for providing key reference to texture design.Mechanical behavior of bimodal textured Mg alloy under tension and compression was tested.CYS/TYS(compressive yield stress/tensile yield stress)equal to 1 is obtained,implying that the yield asymmetry is eliminated when two textures distribute at specific fractions.The corresponding mechanism for the texture-dependence of tension-compression yield asymmetry is revealed by the analysis of slip/twinning activities and a compound use of the activation stress difference of slip/twinning(ΔStress)and geometrical compatibility factor(m′)between neighboring grains.Balanced activity of{10■2}twinning and a quite similar boundary obstacle effect against slip/twinning transfer under tension and compression accounts for such good symmetry performance.
基金partly supported by the National Natural Science Foundation of China(No.51972108)Distinguished Young Scientists of Hunan Province(No.2022JJ10024)+1 种基金Natural Science Foundation of Hunan Province(No.2021JJ30216)Key Projects of Hunan Provincial Education Department(No.22A0412)。
文摘In the face of multiple challenges brought by the changes of global climate and environment,developing clean energy and updating green energy storage equipment are important ways to achieve carbon peak and carbon neutrality.Aqueous batteries have become a research hotspot due to their advantages of using the multivalent charge carrier,high ionic conductivity,environmental friendliness and cost effectiveness.In this work,the Cu_(2)Se@C(Cu_(2)Se coated on carbon clothes)thin film with a three-dimensional braided structure is fabricated by a simple electrochemical deposition method for Cu^(2+)storage for the first time.Compared with the commercial Cu_(2)Se powder,the well-designed Cu_(2)Se@C film shows enhanced specific capacity(640 mAh/g at 0.5 A/g)and rate performance(542 mAh/g at 5 A/g)as well as superior cycling stability(82.7%capacity retention after 1000 cycles at 1 A/g).The Cu^(2+)storage mechanism of the Cu_(2)Se@C electrode is based on a reversible phase transition process of Cu_(2)Se←→Cu_(2-x)Se←→CuSe←→CuSe_(2).In kinetic characteristic analysis,the Cu_(2)Se@C electrode demonstrates faster Cu^(2+)diffusion in discharge process than charge process resulting from the phase transition and the variation of interplanar spacing.This work highlights a facile one-piece design strategy and opens a new gateway for the exploration of advanced aqueous energy storage systems.
基金funded by the National Key R&D Program of China(No.2021YFB3601600)Innovation Support Programme(Soft Science Research)Project Achievements of Jiangsu Province(No.BK20231514)+3 种基金the National Nature Science Foundation of China(Nos.61974062,62004104)the Leading-edge Technology Program of Jiangsu Natural Science Foundation(No.BE2021008–2)The Fundamental Research Foundation for the Central UniversitiesCollaborative Innovation Center of Solid-State Lighting and Energy-Saving Electronics。
文摘High-efficiency hydrogen production through photoelectrochemical(PEC)water splitting has emerged as a promising solution to address current global energy challenges.Ⅲ-nitride semiconductor photoelectrodes with nanostructures have demonstrated great potential in the near future due to their high light absorption,tunable direct band gap,and strong physicochemical stability.However,several issues,including surface trapping centers,surface Fermi level pinning,and surface band bending,need to be addressed.In this work,enhanced photovoltaic properties have been achieved using gallium nitride(GaN)nanowires(NWs)photoelectrodes by adopting an alkaline solution surface treatment method to reduce the surface states.It was found that surface oxides on NWs can be removed by an alkaline solution treatment without changing the surface morphology through X-ray photoelectron spectroscopy(XPS),scanning electron microscopy(SEM)and other characterization methods.These findings provide new insights to the development of high-efficiency photoelectrodes for new energy source applications.
基金financially supported by the Natural Science Foundation of Sichuan Province(2023NSFSC0915)the Postdoctoral Research Project Special Fund of Sichuan Province and Natural Science Starting Project of SWPU(2023QHZ017).
文摘The investigation concentrates on friction stir welded(FSW)Al-Cu-Li alloy concerning its local microstructural evolution and mechanical properties.The grain features were characterized by electron back scattered diffraction(EBSD)technology,while precipitate characterization was conducted by using transmission electron microscopy(TEM)aligned along[011]Al and[001]Al zone axes.The mechanical properties are evaluated through micro-hardness and tensile testing.It can be found that nugget zones exhibit finely equiaxed grains evolved through complete dynamic recrystallization(DRX),primarily occurring in continuous dynamic recrystallization(CDRX)and discontinuous dynamic recrystallization(DDRX).In the thermal-mechanically affected zone(TMAZ),numerous sub-structured grains,exhibiting an elongated morphology,were created due to partial DRX,signifying the dominance of CDRX,DDRX,and geometric dynamic recrystallization(GDRX)in this region.T_(1)completely dissolves in the nugget zone(NZ)leading to the formation of Guinier-Preston zones and increase ofδ′,β′and S′.Conversely,T_(1)partially solubilizes in TMAZ,the lowest hardness zone(LHZ)and heat affected zone(HAZ),and the residual T_(1)undergoes marked coarsening,revealing various T_(1)variants.The solubilization and coarsening of T_(1)are primary contributors to the degradation of hardness and strength.θ′primarily dissolves and coarsens in NZ and TMAZ,whilst this precipitate largely coarsens in HAZ and LHZ.σ,TB,grain boundary phases(GBPs)and precipitate-free zone(PFZ)are newly generated during FSW.σexists in the TMAZ,LHZ and HAZ,whereas TB nucleates in NZ.GBPs and PFZ mostly develop in LHZ and HAZ,which can cause strain localization during tensile deformation,potentially leading to LHZ joint fracture.
文摘In 1957,Macfarlane Burnet proposed the theory that harnessing the body’s immune system could be an effective method for cancer treatment[1].Today,T-cell-based immunotherapies have indeed become a vital part of cancer treatment[2].However,a deeper understanding of antitumor immunity is still necessary to further support these treatments.Notably,CD4^(+)T cells are central to mediating antitumor immune responses[3,4,5,6],yet the cellular and molecular programs governing CD4^(+)T-cell antitumor immunity remain unclear.Our recent research revealed that CD4^(+)T-cell immunity is critically dependent on an intrinsic stem-like program[7].
基金The research received support from internal fund provided by the Houston Methodist Research Institute to W.C.
文摘T-cell-based immunotherapy is gaining momentum in cancer treatment;however,our comprehension of the transcriptional regulation governing T cell antitumor activity remains constrained.The objective of this study was to explore the function of interferon regulatory factor 4(IRF4)in antitumor CD8^(+)T cells using the TRAMP-C1 prostate cancer and B16F10 melanoma model.To achieve this,we generated an Irf4^(GFP-DTR) mouse strain and discovered that CD8^(+)tumor-infiltrating lymphocytes(TILs)expressing high levels of IRF4.GFP exhibited a more differentiated PD-1high cell phenotype.By administering diphtheria toxin to tumor-bearing Irf4^(GFP-DTR) mice,we partially depleted IRF4.GFP^(+)TILs and observed an accelerated tumor growth.To specifically explore the function of IRF4 in antitumor CD8^(+)T cells,we conducted 3 adoptive cell therapy(ACT)models.Firstly,depleting IRF4.GFP^(+)CD8^(+)TILs derived from ACT significantly accelerated tumor growth,emphasizing their crucial role in controlling tumor progression.Secondly,deleting the Irf4 gene in antitumor CD8^(+)T cells used for ACT led to a reduction in the frequency and effector differentiation of CD8^(+)TILs,completely abolishing the antitumor effects of ACT.Lastly,we performed a temporal deletion of the Irf4 gene in antitumor CD8^(+)T cells during ACT,starting from 20 days after tumor implantation,which significantly compromised tumor control.Therefore,sustained expression of IRF4 is essential for maintaining CD8^(+)T cell immunity in the melanoma model,and these findings carry noteworthy implications for the advancement of more potent immunotherapies for solid tumors.
基金the Project of the National Key Research and Development Program of China(No.2021YFC1910404)the National Natural Science Foundation of China(Nos.52100008,52100184,and 52100142)+4 种基金the Funds of Hunan Science and Technology Innovation Project(China)(Nos.2021GK4055 and 2022SK2119)Natural Science Foundation of Hunan ProvinceChina(No.2021JJ40091)the Science and Technology Innovation Program of Hunan Province(China)(No.2021RC2056)the Project funded by China Postdoctoral Science Foundation(No.2021M701149).
文摘Sulfate radicals have been increasingly used for the pathogen inactivation due to their strong redox ability and high selectivity for electron-rich species in the last decade.The application of sulfate radicals in water disinfection has become a very promising technology.However,there is currently a lack of reviews of sulfate radicals inactivated pathogenic microorganisms.At the same time,less attention has been paid to disinfection by-products produced by the use of sulfate radicals to inactivate microorganisms.This paper begins with a brief overview of sulfate radicals’properties.Then,the progress in water disinfection by sulfate radicals is summarized.The mechanism and inactivation kinetics of inactivating microorganisms are briefly described.After that,the disinfection by-products produced by reactions of sulfate radicals with chlorine,bromine,iodide ions and organic halogens in water are also discussed.In response to these possible challenges,this article concludes with some specific solutions and future research directions.
文摘Congenital proximal radioulnar synostosis(CPRUS)is a rare anomaly which is caused by abnormal fusion of the proximal radius and ulna during development.This is due to the failure of embryological separation,resulting in the fixed position of the forearm,from mild to severe pronation.1Mild deformity leads to slight disability because the shoulder and wrist can effectively compensate.2 Patients with bilateral cases and/or pronation defor-mity of>60°may be severely limited in daily activities.34 Most surgeons recommend surgical intervention when the loss of forearm rotation exceeds 60°,particularly when the forearm is fixed in pronation.
基金supported by the National Natural Science Foundation of China (81741087, 91432111, 31625013, and 81471484)the Science and Technology Commission of Shanghai Municipality, China (14411950402)+1 种基金a Shanghai Municipal Science and Technology Major Project (#018SHZDZX05)the Postdoctoral Science Foundation of China (2017M621361)
文摘Early-onset epilepsy is a neurological abnormality in childhood, and it is especially common in the first2 years after birth. Seizures in early life mostly result from structural or metabolic disorders in the brain, and the genetic causes of idiopathic seizures have been extensively investigated. In this study, we identified four missense mutations in the SETD1 A gene(SET domain-containing 1 A, histone lysine methyltransferase): three de novo mutations in three individuals and one inherited mutation in a four-generation family. Whole-exome sequencing indicated that all four of these mutations were responsible for the seizures. Mutations of SETD1 A have been implicated in schizophrenia and developmental disorders, so we examined the role of the four mutations(R913 C, Q269 R, G1369 R, and R1392 H) in neural development. We found that their expression in mouse primary cortical neurons affected excitatory synapse development. Moreover, expression of the R913 C mutation also affected the migration of cortical neurons in the mouse brain.We further identified two common genes(Neurl4 and Usp39) affected by mutations of SETD1 A. These results suggested that the mutations of SETD1 A play a fundamental role in abnormal synaptic function and the development of neurons, so they may be pathogenic factors for neurodevelopmental disorders.
基金supported by American Heart Association Grant 11SDG7690000National Institutes of Health Grant P30 DK079638+1 种基金Fondation de la Recherche en Transplantation Grant IIG201101Jie Wu received financial support from the China Scholarship Council(201306160044).
文摘The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens.This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function.Herein,we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance.We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune tolerance,followed by discussing other cytokines that maintain immune tolerance through inducing CD_(4)^(+) Foxp_(3)^(+) regulatory T cells(Tregs),which negatively control immune cells.Interleukin(IL)-2 is the most potent cytokine in promoting the development and survival of Tregs,thereby mediating immune tolerance.IL-35 is mainly produced by Tregs,but its biology function remains to be defi ned.Finally,we discuss the actions of proinflammatory cytokines that breach immune tolerance and induce autoimmunity,which include IL-7,IL-12,IL-21,and IL-23.Recent genetic studies have revealed the role of these cytokines(or their cognate receptors)in susceptibility to autoimmune diseases.Taken together,we highlight in this review the cytokine regulation of immune tolerance,which will help in further understanding of human diseases that are caused by dysregulated immune system.
基金the Natural Science Foundation of China(#31601206,31171436).
文摘Embryo implantation and decidualization are crucial for successful pregnancy,which include multiple genes and signaling pathways,while the precise mechanism regarding embryo implantation and decidualization has yet to be explored.The GABA which activates GABA_(A)or GABA_(B)receptors has been found playing an important role in early pregnancy.Here we seek to investigate whether GABA_(B)receptors participate in embryo implantation in mice.This study first characterized the spatiotemporal expression pattern of GABA_(B)receptors in the uterus during the peri-implantation period and found that GABA_(B1)expression was drastically upregulated in stromal cells on days 4e6,a period of embryo implantation and early stages of decidualization.Embryo delayed implantation and oil-induced decidualization models were further used to confirm that the GABA_(B1)was associated with embryo implantation and decidualization.We also found estrogen or progesterone had no directly effect on expression of GABA_(B1)in ovariectomized model.Because we were unable to detect significant GABA_(B2)which couples with GABA_(B1)to form whole GABA_(B)receptors,and the agonist and antagonist of whole GABA_(B)receptors had weak effect on the proliferation and differentiation of stromal cells as well,we excluded the possibility whole GABA_(B)receptors function,and concluded it should be non-classical signals of GABA_(B1)involving in embryo implantation and decidualization.Future studies should focus on investigating the roles and mechanisms of GABA_(B1)during embryo implantation and decidualization.
基金supported by National Institutes of Health grants(R01LM012806,R01DE030122,and R01DE029818)Cancer Prevention and Research Institute of Texas(CPRIT RP180734 and RP210045)The funders had no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript.Funding for open access charge:CPRIT(RP180734)。
文摘Understanding the molecular mechanisms of coronavirus disease 2019(COVID-19)pathogenesis and immune response is vital for developing therapies.Single-cell RNA sequencing has been applied to delineate the cellular heterogeneity of the host response toward COVID-19 in multiple tissues and organs.Here,we review the applications and findings from over 80 original COVID-19 single-cell RNA sequencing studies as well as many secondary analysis studies.We describe that single-cell RNA sequencing reveals multiple features of COVID-19 patients with different severity,including cell populations with proportional alteration,COVID-19-induced genes and pathways,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in single cells,and adaptation of immune repertoire.We also collect published single-cell RNA sequencing datasets from original studies.Finally,we discuss the limitations in current studies and perspectives for future advance.