Malignant tumors are a major threat to human health with the immune responses critically influenced by major histocompatibility complex(MHC)class I and Ⅱ molecules.While MHC-I has been extensively studied for its rol...Malignant tumors are a major threat to human health with the immune responses critically influenced by major histocompatibility complex(MHC)class I and Ⅱ molecules.While MHC-I has been extensively studied for its role in tumor immunity,research on MHC-Ⅱ,particularly MHC-Ⅱ function within the tumor microenvironment,has lagged behind research on MHC-Ⅰ.The expression and regulation of tumor-specific MHC-Ⅱ(tsMHC-Ⅱ)in tumor cells not only reflect the immunogenic landscape of the tumor microenvironment but also actively shape antitumor immune responses by modulating CD4^(+)T cell recognition and activation.Expression of tsMHC-Ⅱ is tightly controlled by intrinsic oncogenic signaling and extrinsic cytokine stimulation,positioning tsMHC-Ⅱ as a key determinant of response to immunotherapy,including immune checkpoint blockade.Accordingly,tsMHC-Ⅱ may serve as a predictive biomarker and a potential therapeutic target in tumor immunotherapy.This review highlights recent advances in the structure and function of MHC-Ⅱ,the MHC-Ⅱ regulatory mechanisms in tumors,and the emerging significance of MHC-Ⅱ in guiding future immunotherapeutic strategies.展开更多
Montmorillonite and clinoptilolite zeolite were used as representative materials to prepare calcined clay-cement binary cementitious materials in order to study the effect of calcination treatment on the activation of...Montmorillonite and clinoptilolite zeolite were used as representative materials to prepare calcined clay-cement binary cementitious materials in order to study the effect of calcination treatment on the activation of clay minerals and the activity difference between layered and framed clays in this research.The influence of different calcined clay content(2%,4%,6%,8%,10%)on the fluidity,compressive strength,microstructure,phase change,and hydration heat of cement-based materials were analyzed.The calcined clay improves the fluidity of cement-based materials as compared with the uncalcined group.The addition of calcined montmorillonite(CMT)improves the development of mechanical strength,and the optimal compressive strength reaches 85 MPa at 28 days with 8%CMT.However,the activity of calcined clinoptilolite zeolite(CZL)is weak with few reaction sites,which slightly reduced the mechanical strength as compared to the blank sample.The addition of CMT changes the microscopic morphology of hydration products such as C-S-H and C-A-H,leading to the formation and transformation of ettringite in the early stage.It promotes the gradual polymerization of Si-O bonds into Si-O-Si bonds simultaneously,which accelerates the early hydration process.However,CZL acts mainly as a filling function in the cementitious system.In brief,CMT as an admixture can improve the mechanical properties of cement,but CZL has little effect.This work provides a guideline for the applications of calcined clay in cement,considering the influence of clay type on workability and mechanical strength.展开更多
The apoptosis of glomerular mesangial cells(GMCs)is considered to be an important contributor to the initiation and development of rat Thy-1 nephritis(Thy-1N)and is accompanied by sublytic C5b-9 deposition.However,the...The apoptosis of glomerular mesangial cells(GMCs)is considered to be an important contributor to the initiation and development of rat Thy-1 nephritis(Thy-1N)and is accompanied by sublytic C5b-9 deposition.However,the mechanism by which sublytic C5b-9 triggers GMC apoptosis has not been elucidated.In this study,functional and histological examinations were performed on GMCs treated with sublytic C5b-9(in vitro)and renal tissues of Thy-1N rats(in vivo).The in vitro studies found that sublytic C5b-9 could trigger GMC apoptosis through upregulating Egr-1,ATF3,and Gadd45 expression.Egr-1-mediated post-transcriptional modulation of ATF3,Egr-1/ATF3-enhanced Gadd45 promoter activity,and p300-mediated ATF3 acetylation were all involved in GMC apoptosis.More importantly,the effective binding elements for Egr-1 and ATF3 to Gadd45β/γpromoters and the ATF3 acetylation site were identified.In vivo,silencing renal p300,Egr-1,ATF3,and Gadd45β/γsignificantly decreased GMC apoptosis,secondary GMC proliferation,and urinary protein secretion in Thy-1N rats.Together,these findings implicate that sublytic C5b-9-induced activation of Egr-1/p300–ATF3/Gadd45 axis plays a critical role in GMC apoptosis in Thy-1N rats.展开更多
基金supported by The National Key Research and Development Program of China(2021YFA0910100)Healthy Zhejiang One Million People Cohort(K-20230085)+4 种基金National Natural Science Foundation of China(82304946,82473489,and 82403546)Post-doctoral Innovative Talent Support Program(BX2023375)Natural Science Foundation of Zhejiang Province(LR21H280001)China Postdoctoral Science Foundation(2023M743560)The Medicine and Health Science Fund of Zhejiang Province Health Commission(2025KY047).
文摘Malignant tumors are a major threat to human health with the immune responses critically influenced by major histocompatibility complex(MHC)class I and Ⅱ molecules.While MHC-I has been extensively studied for its role in tumor immunity,research on MHC-Ⅱ,particularly MHC-Ⅱ function within the tumor microenvironment,has lagged behind research on MHC-Ⅰ.The expression and regulation of tumor-specific MHC-Ⅱ(tsMHC-Ⅱ)in tumor cells not only reflect the immunogenic landscape of the tumor microenvironment but also actively shape antitumor immune responses by modulating CD4^(+)T cell recognition and activation.Expression of tsMHC-Ⅱ is tightly controlled by intrinsic oncogenic signaling and extrinsic cytokine stimulation,positioning tsMHC-Ⅱ as a key determinant of response to immunotherapy,including immune checkpoint blockade.Accordingly,tsMHC-Ⅱ may serve as a predictive biomarker and a potential therapeutic target in tumor immunotherapy.This review highlights recent advances in the structure and function of MHC-Ⅱ,the MHC-Ⅱ regulatory mechanisms in tumors,and the emerging significance of MHC-Ⅱ in guiding future immunotherapeutic strategies.
基金The research presented in this paper was supported by National Natural Science Foundation of China(Grant No.52272031)the Fundamental Research Funds for the Central Universities,China University of Geosciences(Wuhan),and the Opening Fund of Guangxi Key Laboratory of New Energy and Building Energy Saving(Grant No.19-J-22-2)+3 种基金Key Research and Development Program of Hubei Province(Grant No.2020BAB065)Key Research and Development Program of Jiangxi Province(Grant No.20201BBG71011)Fundamental Research Funds for the Central Universities,CHD(Grant No.300102211506)Opening Fund of Key Laboratory of Advanced Building Materials of Anhui Province(Grant No.JZCL001KF).
文摘Montmorillonite and clinoptilolite zeolite were used as representative materials to prepare calcined clay-cement binary cementitious materials in order to study the effect of calcination treatment on the activation of clay minerals and the activity difference between layered and framed clays in this research.The influence of different calcined clay content(2%,4%,6%,8%,10%)on the fluidity,compressive strength,microstructure,phase change,and hydration heat of cement-based materials were analyzed.The calcined clay improves the fluidity of cement-based materials as compared with the uncalcined group.The addition of calcined montmorillonite(CMT)improves the development of mechanical strength,and the optimal compressive strength reaches 85 MPa at 28 days with 8%CMT.However,the activity of calcined clinoptilolite zeolite(CZL)is weak with few reaction sites,which slightly reduced the mechanical strength as compared to the blank sample.The addition of CMT changes the microscopic morphology of hydration products such as C-S-H and C-A-H,leading to the formation and transformation of ettringite in the early stage.It promotes the gradual polymerization of Si-O bonds into Si-O-Si bonds simultaneously,which accelerates the early hydration process.However,CZL acts mainly as a filling function in the cementitious system.In brief,CMT as an admixture can improve the mechanical properties of cement,but CZL has little effect.This work provides a guideline for the applications of calcined clay in cement,considering the influence of clay type on workability and mechanical strength.
基金supported by grants from the National Natural Science Foundations of China(81273333,81471626,and 31470853)the Natural Science Foundation of Jiangsu Higher Education Institutions of China(14KJB310006)supported by Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions.
文摘The apoptosis of glomerular mesangial cells(GMCs)is considered to be an important contributor to the initiation and development of rat Thy-1 nephritis(Thy-1N)and is accompanied by sublytic C5b-9 deposition.However,the mechanism by which sublytic C5b-9 triggers GMC apoptosis has not been elucidated.In this study,functional and histological examinations were performed on GMCs treated with sublytic C5b-9(in vitro)and renal tissues of Thy-1N rats(in vivo).The in vitro studies found that sublytic C5b-9 could trigger GMC apoptosis through upregulating Egr-1,ATF3,and Gadd45 expression.Egr-1-mediated post-transcriptional modulation of ATF3,Egr-1/ATF3-enhanced Gadd45 promoter activity,and p300-mediated ATF3 acetylation were all involved in GMC apoptosis.More importantly,the effective binding elements for Egr-1 and ATF3 to Gadd45β/γpromoters and the ATF3 acetylation site were identified.In vivo,silencing renal p300,Egr-1,ATF3,and Gadd45β/γsignificantly decreased GMC apoptosis,secondary GMC proliferation,and urinary protein secretion in Thy-1N rats.Together,these findings implicate that sublytic C5b-9-induced activation of Egr-1/p300–ATF3/Gadd45 axis plays a critical role in GMC apoptosis in Thy-1N rats.
