Epstein-Barr virus(EBV),a human gammaherpesvirus carried by more than 90% of the world's population,is associated with malignant tumors such as Burkitt's lymphoma(BL),Hodgkin lymphoma,post-transplant lymphoma,...Epstein-Barr virus(EBV),a human gammaherpesvirus carried by more than 90% of the world's population,is associated with malignant tumors such as Burkitt's lymphoma(BL),Hodgkin lymphoma,post-transplant lymphoma,extra-nodal natural killer/T cell lymphoma,and nasopharyngeal and gastric carcinomas in immune-compromised patients.In the process of infection,EBV faces challenges:the host cell environment is harsh,and the survival and apoptosis of host cells are precisely regulated.Only when host cells receive sufficient survival signals may they immortalize.To establish efficiently a lytic or long-term latent infection,EBV must escape the host cell immunologic mechanism and resist host cell apoptosis by interfering with multiple signaling pathways.This review details the apoptotic pathway disrupted by EBV in EBV-infected cells and describes the interactions of EBV gene products with host cellular factors as well as the function of these factors,which decide the fate of the host cell.The relationships between other EBV-encoded genes and proteins of the B-cell leukemia/lymphoma(Bcl) family are unknown.Still,EBV seems to contribute to establishing its own latency and the formation of tumors by modifying events that impact cell survival and proliferation as well as the immune response of the infected host.We discuss potential therapeutic drugs to provide a foundation for further studies of tumor pathogenesis aimed at exploiting novel therapeutic strategies for EBV-associated diseases.展开更多
Bamboo is a green construction material in line with sustainable development strategies.The use of raw bamboo in architecture has existed since ancient times.In the long development years of original bamboo buildings,...Bamboo is a green construction material in line with sustainable development strategies.The use of raw bamboo in architecture has existed since ancient times.In the long development years of original bamboo buildings,many areas in the world gradually formed unique bamboo buildings,which have become an important local cultural feature.For building structures,joints are the key to ensure structural load transfer.Because of hollow and thin-walled material property of bamboo,the connection in raw bamboo buildings has always been a major difficulty and problem in the application of bamboo,which seriously hinders the development of original bamboo structures.In order to promote the use of raw bamboo,two traditional connection methods in raw bamboo structures are described in this paper firstly,with the advantages and disadvantages of the two methods pointed out.Also,research progress on four categories of raw bamboo building joints is described namely,bolt joints,steel member joints,filler reinforced joints and other types of joints.This work can provide a reference for future research and engineering applications.展开更多
Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,...Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.展开更多
Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated tha...Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal（BMS） cells derived from Chip^-/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^-/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.展开更多
Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body.Dissecting the regulatory mechanism of carotenoid metabolism in plants repre...Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body.Dissecting the regulatory mechanism of carotenoid metabolism in plants represents the first step toward manipulating carotenoid contents in plants by molecular design breeding.In this study,we determined that SlAP2c,an APETALA2(AP2)family member,acts as a transcriptional repressor to regulate carotenoid biosynthesis in tomato(Solanum lycopersicum).Knockout of SlAP2c in both the“Micro Tom”and“Ailsa Craig”backgrounds resulted in greater lycopene accumulation,whereas overexpression of this gene led to orange-ripe fruit with significantly lower lycopene contents than the wild type.We established that SlAP2c represses the expression of genes involved in lycopene biosynthesis by directly binding to the cis-elements in their promoters.Moreover,SlAP2c relies on its EAR motif to recruit the co-repressors TOPLESS(TPL)2/4 and forms a complex with histone deacetylase(had)1/3,thereby reducing the histone acetylation levels of lycopene biosynthesis genes.Furthermore,SlAP2a,a homolog of SlAP2c,acts upstream of SlAP2c and alleviates the SlAP2c-induced repression of lycopene biosynthesis genes by inhibiting SlAP2c transcription during fruit ripening.Therefore,we identified a transcriptional cascade mediated by AP2 family members that regulates lycopene biosynthesis during fruit ripening in tomato,laying the foundation for the manipulation of carotenoid metabolism in plants.展开更多
基金Project supported by the National Natural Science Foundation of China (No.81071937)the Qianjiang Talents Project of Technology Office in Zhejiang Province,China (No.2010R10064)
文摘Epstein-Barr virus(EBV),a human gammaherpesvirus carried by more than 90% of the world's population,is associated with malignant tumors such as Burkitt's lymphoma(BL),Hodgkin lymphoma,post-transplant lymphoma,extra-nodal natural killer/T cell lymphoma,and nasopharyngeal and gastric carcinomas in immune-compromised patients.In the process of infection,EBV faces challenges:the host cell environment is harsh,and the survival and apoptosis of host cells are precisely regulated.Only when host cells receive sufficient survival signals may they immortalize.To establish efficiently a lytic or long-term latent infection,EBV must escape the host cell immunologic mechanism and resist host cell apoptosis by interfering with multiple signaling pathways.This review details the apoptotic pathway disrupted by EBV in EBV-infected cells and describes the interactions of EBV gene products with host cellular factors as well as the function of these factors,which decide the fate of the host cell.The relationships between other EBV-encoded genes and proteins of the B-cell leukemia/lymphoma(Bcl) family are unknown.Still,EBV seems to contribute to establishing its own latency and the formation of tumors by modifying events that impact cell survival and proliferation as well as the immune response of the infected host.We discuss potential therapeutic drugs to provide a foundation for further studies of tumor pathogenesis aimed at exploiting novel therapeutic strategies for EBV-associated diseases.
基金supported by the Natural Science Foundation of Jiang-su Province(No.BK20181402)the National Natural Science Foundation of China(51878354)+2 种基金National Key R&D Program of China,the Open Fund Project from Key Laboratory of Concrete and Pre-stressed Concrete Structure of Ministry of Education(Southeast university)the China Postdoctoral Science Foundation(2015M580382)Jiangsu Postdoctoral Science Foundation Project(1501037A),Qing Lan Project,and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Bamboo is a green construction material in line with sustainable development strategies.The use of raw bamboo in architecture has existed since ancient times.In the long development years of original bamboo buildings,many areas in the world gradually formed unique bamboo buildings,which have become an important local cultural feature.For building structures,joints are the key to ensure structural load transfer.Because of hollow and thin-walled material property of bamboo,the connection in raw bamboo buildings has always been a major difficulty and problem in the application of bamboo,which seriously hinders the development of original bamboo structures.In order to promote the use of raw bamboo,two traditional connection methods in raw bamboo structures are described in this paper firstly,with the advantages and disadvantages of the two methods pointed out.Also,research progress on four categories of raw bamboo building joints is described namely,bolt joints,steel member joints,filler reinforced joints and other types of joints.This work can provide a reference for future research and engineering applications.
文摘Cytokines play pleiotropic roles in human health and disease by regulating both innate and adaptive immune responses.Interleukins(ILs),a large group of cytokines,can be divided into seven families,including IL-1,IL-2,IL-6,IL-8,IL-10,IL-12,and IL-17 families.Here,we review the functions of ILs in the pathogenesis and resolution of liver diseases,such as liver inflammation(e.g.,IL-35),alcoholrelated liver disease(e.g.,IL-11),non-alcoholic steatohepatitis(e.g.,IL-22),liver fibrosis(e.g.,Il-17a),and liver cancer(e.g.,IL-8).Overall,IL-1 family members are implicated in liver inflammation induced by different etiologies,such as alcohol consumption,high-fat diet,and hepatitis viruses.IL-2 family members mainly regulate T lymphocyte and NK cell proliferation and activation,and the differentiation of T cells.IL-6 family cytokines play important roles in acute phase response in liver infection,liver regeneration,and metabolic regulation,as well as lymphocyte activation.IL-8,also known as CXCL8,is activated in chronic liver diseases,which is associated with the accumulation of neutrophils and macrophages.IL-10 family members contribute key roles to liver immune tolerance and immunosuppression in liver disease.IL-12 family cytokines influence T-cell differentiation and play an essential role in autoimmune liver disease.IL-17 subfamilies contribute to infection defense,liver inflammation,and Th17 cell differentiation.ILs interact with different type I and type II cytokine receptors to regulate intracellular signaling pathways that mediate their functions.However,most clinical studies are only performed to evaluate IL-mediated therapies on alcohol and hepatitis virus infection-induced hepatitis.More pre-clinical and clinical studies are required to evaluate IL-mediated monotherapy and synergistic therapies.
基金supported by National Institutes of Health Grants, R01 AR054465, R01 AR070222, and R01 AR070222supported by the grants of Natural Science Foundation of China (NSFC) to TW (grants No. 81301531 and 81572104)+1 种基金supported by the grant from Shenzhen Science and Technology Innovation Committee, China (grant No. JCYJ20160331114205502)the grant from Shenzhen Development and Reform Committee, China for Shenzhen Engineering Laboratory of Orthopedic Regenerative Technologies
文摘Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal（BMS） cells derived from Chip^-/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^-/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.
基金supported in part by the National Natural Science Foundation of China(no.32372780,no.32172643)the Applied Basic Research Category of Science and Technology Program of Sichuan Province(2021YFQ0071,2022YFSY0059-1,2021YFYZ00105-LH)+2 种基金the Technology Innovation and Application Development Program of Chongqing(cstc2021jscx-cylh X0001)the Natural Science Foundation of Sichuan Province,China(2023NSFSC1991)the Institutional Research Funding of Sichuan University(2022SCUNL105)。
文摘Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body.Dissecting the regulatory mechanism of carotenoid metabolism in plants represents the first step toward manipulating carotenoid contents in plants by molecular design breeding.In this study,we determined that SlAP2c,an APETALA2(AP2)family member,acts as a transcriptional repressor to regulate carotenoid biosynthesis in tomato(Solanum lycopersicum).Knockout of SlAP2c in both the“Micro Tom”and“Ailsa Craig”backgrounds resulted in greater lycopene accumulation,whereas overexpression of this gene led to orange-ripe fruit with significantly lower lycopene contents than the wild type.We established that SlAP2c represses the expression of genes involved in lycopene biosynthesis by directly binding to the cis-elements in their promoters.Moreover,SlAP2c relies on its EAR motif to recruit the co-repressors TOPLESS(TPL)2/4 and forms a complex with histone deacetylase(had)1/3,thereby reducing the histone acetylation levels of lycopene biosynthesis genes.Furthermore,SlAP2a,a homolog of SlAP2c,acts upstream of SlAP2c and alleviates the SlAP2c-induced repression of lycopene biosynthesis genes by inhibiting SlAP2c transcription during fruit ripening.Therefore,we identified a transcriptional cascade mediated by AP2 family members that regulates lycopene biosynthesis during fruit ripening in tomato,laying the foundation for the manipulation of carotenoid metabolism in plants.
