In the past decade,chimeric antigen receptor(CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers,demonstrating remarkable efficacy in relapsed/refractory hematological malig...In the past decade,chimeric antigen receptor(CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers,demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients.CAR-natural killer(CAR-NK)cell complements CAR-T cell therapy by offering several distinct advantages.CAR-NK cells do not require HLA compatibility and exhibit low safety concerns.Moreover,CAR-NK cells are conducive to“off-the-shelf”therapeutics,providing significant logistic advantages over CAR-T cells.Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies.However,their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration,as well as an immuno-suppressive tumor microenvironment.In this review,we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies,with a specific focus on the obstacles to their application in solid tumors.We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization.Finally,we explore future perspectives of these adoptive immunotherapies,highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.展开更多
Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, hea...Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 （HSP47） is closely related with the development of fbrosis. To explore the potential func- tion of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed. In clinical, the increased mRNA level of HSP47 was observed in the skin fibroblasts and PBMC from scle- roderma patients, and the enhanced protein level of HSP47 was also detected in the skin biopsy and plasma of the above patients. Unexpectedly, the enhanced levels of HSP47 were positively correlated with the presence of anti-centromere antibody in scleroderma patients. Moreover, a high expression of HSP47 was found in the skin lesion of BLM-induced scleroderma mouse model. Further in vitro studies demonstrated that HSP47 knockdown could block the intracellular and extracellular collagen over-productions induced by exogenous TGF-13. Therefore, the results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma. The high expression of HSP47 can be detected in the circulatory system of scleroderma patients, indicating that HSP47 maybecome a pathological marker to assess the progres- sion of scleroderma, and also explain the systemic fibrosis of scleroderma. Meanwhile, collagen over-ex- pression is blocked by HSP47 knockdown, suggesting the possibility that HSP47 can be a potential therapeutic target for scleroderma.展开更多
Summary What is already known about this topic?In recent years,there has been a significant increase in the proportion of women of advanced maternal age(AMA),accompanied by a rise in adverse pregnancy outcomes in cert...Summary What is already known about this topic?In recent years,there has been a significant increase in the proportion of women of advanced maternal age(AMA),accompanied by a rise in adverse pregnancy outcomes in certain regions of China.What is added by this report?From 2016 to 2022,there was an observed increase in the proportion of AMA,educational levels,and incidences of preterm birth and low birth weight(LBW)in both primiparous and multiparous women.Concurrently,there was a declining trend in the rate of cesarean deliveries and the incidence of macrosomia among multiparous women.What are the implications for public health practice?In addition to focusing on health management for AMA individuals,proactive steps should be undertaken to enhance the quality of medical services and promote childbirth at optimal ages,thereby reducing the incidence of adverse pregnancy outcomes.展开更多
Summary What is already known about this topic?Low fertility rates have become the most important risk affecting the balanced development of the population in China.What is added by this report?About 80.0%of childless...Summary What is already known about this topic?Low fertility rates have become the most important risk affecting the balanced development of the population in China.What is added by this report?About 80.0%of childless women had fertility intentions,31.9%of women with one child and 11.3%of women with two children intended to have a second and third child,respectively.Women with one child who had an agricultural Hukou*,were younger than 30 years old,were remarried,and had received a deduction or reimbursement for childbirth expenses during their first delivery were more willing to have a second child.Women with two children who had an agricultural Hukou and a upper-middle personal income,were selfemployed,and had two daughters were more willing to have a third child.What are the implications for public health practice?In China,women’s willingness to have more children is not optimistic.To increase their desire for more children,creating a more favorable fertility environment for reproductive-age women and providing more preferential fertility policies for pregnant women will be necessary.展开更多
Dear Editor,SARS-CoV-2 rapidly evolves during the pandemic1 with many variants of concern(VoCs)lineages(Supplementary Fig.S1a).Omicron(B.1.1.529)and its sub-lineages led to multiple infection waves globally.2 Omicron ...Dear Editor,SARS-CoV-2 rapidly evolves during the pandemic1 with many variants of concern(VoCs)lineages(Supplementary Fig.S1a).Omicron(B.1.1.529)and its sub-lineages led to multiple infection waves globally.2 Omicron subvariants harbored a high number of mutations,especially in the spike(S)glycoprotein,and clustered in the receptor-binding domain(RBD)(Supplementary Fig.S1b,c;Supplemental Discussion).These subvariants drastically decrease the efficacy of current vaccinations and monoclonal antibody therapies.展开更多
基金SC is supported by the Cancer Research Institute Lloyd J.Old STAR Award(CRI4964),NIH(R33CA281702)DoD(W81XWH-21-1-0514,HT94252310472)Pershing Square Sohn Cancer Research Alliance.
文摘In the past decade,chimeric antigen receptor(CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers,demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients.CAR-natural killer(CAR-NK)cell complements CAR-T cell therapy by offering several distinct advantages.CAR-NK cells do not require HLA compatibility and exhibit low safety concerns.Moreover,CAR-NK cells are conducive to“off-the-shelf”therapeutics,providing significant logistic advantages over CAR-T cells.Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies.However,their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration,as well as an immuno-suppressive tumor microenvironment.In this review,we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies,with a specific focus on the obstacles to their application in solid tumors.We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization.Finally,we explore future perspectives of these adoptive immunotherapies,highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.
基金This study was partially supported by the grants from the National Science Foundation of China （81270120, 81470254）, International S ＆ T Cooperation Program of China （2013DFA30870）, the 111 Project （B13016）, the Science and Technology Committee of Shanghai Municipality （10JC1402100）, and US NIH NIAID U01 （1U01AI090909）. The computations involved in this study were supported by Fudan University High-End Computing Center.
文摘Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 （HSP47） is closely related with the development of fbrosis. To explore the potential func- tion of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed. In clinical, the increased mRNA level of HSP47 was observed in the skin fibroblasts and PBMC from scle- roderma patients, and the enhanced protein level of HSP47 was also detected in the skin biopsy and plasma of the above patients. Unexpectedly, the enhanced levels of HSP47 were positively correlated with the presence of anti-centromere antibody in scleroderma patients. Moreover, a high expression of HSP47 was found in the skin lesion of BLM-induced scleroderma mouse model. Further in vitro studies demonstrated that HSP47 knockdown could block the intracellular and extracellular collagen over-productions induced by exogenous TGF-13. Therefore, the results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma. The high expression of HSP47 can be detected in the circulatory system of scleroderma patients, indicating that HSP47 maybecome a pathological marker to assess the progres- sion of scleroderma, and also explain the systemic fibrosis of scleroderma. Meanwhile, collagen over-ex- pression is blocked by HSP47 knockdown, suggesting the possibility that HSP47 can be a potential therapeutic target for scleroderma.
文摘Summary What is already known about this topic?In recent years,there has been a significant increase in the proportion of women of advanced maternal age(AMA),accompanied by a rise in adverse pregnancy outcomes in certain regions of China.What is added by this report?From 2016 to 2022,there was an observed increase in the proportion of AMA,educational levels,and incidences of preterm birth and low birth weight(LBW)in both primiparous and multiparous women.Concurrently,there was a declining trend in the rate of cesarean deliveries and the incidence of macrosomia among multiparous women.What are the implications for public health practice?In addition to focusing on health management for AMA individuals,proactive steps should be undertaken to enhance the quality of medical services and promote childbirth at optimal ages,thereby reducing the incidence of adverse pregnancy outcomes.
文摘Summary What is already known about this topic?Low fertility rates have become the most important risk affecting the balanced development of the population in China.What is added by this report?About 80.0%of childless women had fertility intentions,31.9%of women with one child and 11.3%of women with two children intended to have a second and third child,respectively.Women with one child who had an agricultural Hukou*,were younger than 30 years old,were remarried,and had received a deduction or reimbursement for childbirth expenses during their first delivery were more willing to have a second child.Women with two children who had an agricultural Hukou and a upper-middle personal income,were selfemployed,and had two daughters were more willing to have a third child.What are the implications for public health practice?In China,women’s willingness to have more children is not optimistic.To increase their desire for more children,creating a more favorable fertility environment for reproductive-age women and providing more preferential fertility policies for pregnant women will be necessary.
基金LBMS is supported by the DOE Office of Biological and Environmental Research(KP1607011)We thank Drs.Lucas,Klein,L Chen,Müschen,Mr.Monteiro,and others for support+1 种基金This work is supported by DoD PRMRP IIAR(W81XWH-21-1-0019)discretionary funds to SC and NIH R01 AI163395 to Y.X.
文摘Dear Editor,SARS-CoV-2 rapidly evolves during the pandemic1 with many variants of concern(VoCs)lineages(Supplementary Fig.S1a).Omicron(B.1.1.529)and its sub-lineages led to multiple infection waves globally.2 Omicron subvariants harbored a high number of mutations,especially in the spike(S)glycoprotein,and clustered in the receptor-binding domain(RBD)(Supplementary Fig.S1b,c;Supplemental Discussion).These subvariants drastically decrease the efficacy of current vaccinations and monoclonal antibody therapies.
