Immune thrombocytopenia(ITP)is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury.ITP has complicated immunopathological mechanisms that need further elucidation.It is well known that ...Immune thrombocytopenia(ITP)is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury.ITP has complicated immunopathological mechanisms that need further elucidation.It is well known that the costimulatory molecules OX40 ligand(OX40L)and OX40 play essential roles in the immunological mechanisms of autoimmune diseases.Previously,we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells(PBMCs)of ITP patients.In our present study,OX40L-induced follicular helper T(Tfh)cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator(ICOS),programmed cell death protein-1(PD-1),and cluster of differentiation 40 ligand(CD40L)in vitro.Moreover,aberrant OX40L-OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo,inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model,which might accelerate the progression of ITP.Additionally,signal transduction through the OX40L-OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor(TRAF)-nuclear factor-κB(NF-κB)and Janus kinase(JAK)-signal transducer and activator of transcription(STAT)signaling pathways.Overall,OX40L-OX40 signaling is proposed as a potential novel therapeutic target for ITP.展开更多
Owing to the rapid development of microgrids(MGs)and growing applications of renewable energy resources,multiobjective optimal dispatch of MGs need to be studied in detail.In this study,a multiobjective optimal dispat...Owing to the rapid development of microgrids(MGs)and growing applications of renewable energy resources,multiobjective optimal dispatch of MGs need to be studied in detail.In this study,a multiobjective optimal dispatch model is developed for a standalone MG composed of wind turbines,photovoltaics,diesel engine unit,load,and battery energy storage system.The economic cost,environmental concerns,and power supply consistency are expressed via subobjectives with varying priorities.Then,the analytic hierarchy process algorithm is employed to reasonably specify the weight coefficients of the subobjectives.The quantum particle swarm optimization algorithm is thereafter employed as a solution to achieve optimal dispatch of the MG.Finally,the validity of the proposed model and solution methodology are con firmed by case studies.This study provides refere nee for mathematical model of multiojective optimizati on of MG and can be widely used in current research field.展开更多
High nitrogen and nickel-free austenitic stainless steel has received much recognition worldwide because it can solve the problem of ＂nickel-allergy＂ and has outstanding mechanical and physical properties. In this a...High nitrogen and nickel-free austenitic stainless steel has received much recognition worldwide because it can solve the problem of ＂nickel-allergy＂ and has outstanding mechanical and physical properties. In this article, 0Cr17Mn11Mo3N was prepared by powder injection molding （PIM） technique accompanied with solid-nitriding. The results show that the critical solid loading can achieve up to 64vol% by use of gas-atomized powders with the average size of 17.4 μm. The optimized sintefing conditions are determined to be 1300℃,2 h in flowing nitrogen atmosphere, at which the relative density reaches to 99% and the N content is as high as 0.78wt%. After solution annealing at 1150℃for 90 rain and water quench, the 0.2% yield strength, ultimate tensile strength （UTS）, elongation, reduction in area, and hardness can reach as high as 580 MPa, 885 MPa, 26.0%, 29.1%, and Hv 222, respectively.展开更多
Red blood cell(RBC)transfusion is a clinically effective therapy in anemia,for example in patients with malignancies(Shander et al.,2020),bleeding(Odutayo et al.,2017),and preoperative anemia(Pad-manabhan et al.,2019)...Red blood cell(RBC)transfusion is a clinically effective therapy in anemia,for example in patients with malignancies(Shander et al.,2020),bleeding(Odutayo et al.,2017),and preoperative anemia(Pad-manabhan et al.,2019).The past few decades have witnessed a shortage of blood for transfusion due to limited health insurance coverage for blood use and the rapid expansion of hospitals(Chen et al.,2011;Shi et al.,2014).Blood donation levels may easily be affected by general changes in the environment,policy,major events such as disasters,and public sentiment(Hu et al.,2019).展开更多
Glucocorticoid-induced tumor-necrosis factor receptor(GITR)and its ligand,GITRL,play significant roles in regulating immune responses.It is clear that human soluble GITRL(hsGITRL)transduces signal activity through mul...Glucocorticoid-induced tumor-necrosis factor receptor(GITR)and its ligand,GITRL,play significant roles in regulating immune responses.It is clear that human soluble GITRL(hsGITRL)transduces signal activity through multiple oligomerization states.To develop human soluble trimeric GITRL protein as a potential therapeutic target,we explored the link of the isoleucine-zipper(ILZ)motif to the N-terminus of the human soluble GITRL with two leucine sequences.hsGITRL,with the ILZ motif(ILZ-hsGITRL),was firstly expressed in Escherichia coli,which exhibited a predominant trimer when identified by Sephadex G-100 filtration and non-reducing SDS–polyacrylamide gel electrophoresis(SDS-PAGE).The significantly higher biological activity of the ILZ-hsGITRL compared with hsGITRL was confirmed by CD41 T proliferation,interferon-c(IFN-c)secretion and binding activity assay.To reveal and compare the underlying mechanisms,the level of extracellular signal-regulated kinase-1/2(ERK1/2)phosphorylation was examined,indicating that ILZ-hsGITRL induced more persistent and stronger ERK1/2 activation than hsGITRL.In conclusion,the incorporation of an ILZ motif could markedly improve the costimulation of hsGITRL.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82172335,81971994,91846103,and 81871709)the Zhejiang Provincial Key Research and Development Program(No.2020C03032),China.
文摘Immune thrombocytopenia(ITP)is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury.ITP has complicated immunopathological mechanisms that need further elucidation.It is well known that the costimulatory molecules OX40 ligand(OX40L)and OX40 play essential roles in the immunological mechanisms of autoimmune diseases.Previously,we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells(PBMCs)of ITP patients.In our present study,OX40L-induced follicular helper T(Tfh)cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator(ICOS),programmed cell death protein-1(PD-1),and cluster of differentiation 40 ligand(CD40L)in vitro.Moreover,aberrant OX40L-OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo,inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model,which might accelerate the progression of ITP.Additionally,signal transduction through the OX40L-OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor(TRAF)-nuclear factor-κB(NF-κB)and Janus kinase(JAK)-signal transducer and activator of transcription(STAT)signaling pathways.Overall,OX40L-OX40 signaling is proposed as a potential novel therapeutic target for ITP.
基金State Grid Corporation Science and Technology Project(520605190010).
文摘Owing to the rapid development of microgrids(MGs)and growing applications of renewable energy resources,multiobjective optimal dispatch of MGs need to be studied in detail.In this study,a multiobjective optimal dispatch model is developed for a standalone MG composed of wind turbines,photovoltaics,diesel engine unit,load,and battery energy storage system.The economic cost,environmental concerns,and power supply consistency are expressed via subobjectives with varying priorities.Then,the analytic hierarchy process algorithm is employed to reasonably specify the weight coefficients of the subobjectives.The quantum particle swarm optimization algorithm is thereafter employed as a solution to achieve optimal dispatch of the MG.Finally,the validity of the proposed model and solution methodology are con firmed by case studies.This study provides refere nee for mathematical model of multiojective optimizati on of MG and can be widely used in current research field.
文摘High nitrogen and nickel-free austenitic stainless steel has received much recognition worldwide because it can solve the problem of ＂nickel-allergy＂ and has outstanding mechanical and physical properties. In this article, 0Cr17Mn11Mo3N was prepared by powder injection molding （PIM） technique accompanied with solid-nitriding. The results show that the critical solid loading can achieve up to 64vol% by use of gas-atomized powders with the average size of 17.4 μm. The optimized sintefing conditions are determined to be 1300℃,2 h in flowing nitrogen atmosphere, at which the relative density reaches to 99% and the N content is as high as 0.78wt%. After solution annealing at 1150℃for 90 rain and water quench, the 0.2% yield strength, ultimate tensile strength （UTS）, elongation, reduction in area, and hardness can reach as high as 580 MPa, 885 MPa, 26.0%, 29.1%, and Hv 222, respectively.
基金supported by the National Natural Science Foundation of China(Nos.91846103 and 81971994)the Zhejiang Provincial Key Research and Development Program(No.2020C03032),China。
文摘Red blood cell(RBC)transfusion is a clinically effective therapy in anemia,for example in patients with malignancies(Shander et al.,2020),bleeding(Odutayo et al.,2017),and preoperative anemia(Pad-manabhan et al.,2019).The past few decades have witnessed a shortage of blood for transfusion due to limited health insurance coverage for blood use and the rapid expansion of hospitals(Chen et al.,2011;Shi et al.,2014).Blood donation levels may easily be affected by general changes in the environment,policy,major events such as disasters,and public sentiment(Hu et al.,2019).
基金supported by the National Natural Science Foundation of China(Grant No.30871193 and No.30972748)Natural Science Foundation of Jiangsu Province(Grant No.BK2004405)+2 种基金Natural Science Foundation of Jiangsu Province Educational Commission(Grant No.08KJB320002)Research Foundation of Jiangsu Province Health Department(Grant No.H200952)Top Talent Program of Jiangsu University and SCI-Tech Innovation Team of Jiangsu University。
文摘Glucocorticoid-induced tumor-necrosis factor receptor(GITR)and its ligand,GITRL,play significant roles in regulating immune responses.It is clear that human soluble GITRL(hsGITRL)transduces signal activity through multiple oligomerization states.To develop human soluble trimeric GITRL protein as a potential therapeutic target,we explored the link of the isoleucine-zipper(ILZ)motif to the N-terminus of the human soluble GITRL with two leucine sequences.hsGITRL,with the ILZ motif(ILZ-hsGITRL),was firstly expressed in Escherichia coli,which exhibited a predominant trimer when identified by Sephadex G-100 filtration and non-reducing SDS–polyacrylamide gel electrophoresis(SDS-PAGE).The significantly higher biological activity of the ILZ-hsGITRL compared with hsGITRL was confirmed by CD41 T proliferation,interferon-c(IFN-c)secretion and binding activity assay.To reveal and compare the underlying mechanisms,the level of extracellular signal-regulated kinase-1/2(ERK1/2)phosphorylation was examined,indicating that ILZ-hsGITRL induced more persistent and stronger ERK1/2 activation than hsGITRL.In conclusion,the incorporation of an ILZ motif could markedly improve the costimulation of hsGITRL.
