c-Met is a hepatocyte growth factor receptor overexpressed in many tumors such as hepatocellular carcinoma(HCC).Therefore,c-Met may serve as a promising target for HCC immunotherapy.Modifying T cells to express c-Met-...c-Met is a hepatocyte growth factor receptor overexpressed in many tumors such as hepatocellular carcinoma(HCC).Therefore,c-Met may serve as a promising target for HCC immunotherapy.Modifying T cells to express c-Met-specific chimeric antigen receptor(CAR)is an attractive strategy in treating c-Met-positive HCC.This study aimed to systematically evaluate the inhibitory effects of 2^(nd)-and 3^(rd)-generation c-Met CAR-T cells on hepatocellular carcinoma(HCC)cells.Here,2^(nd)-and 3^(rd)-generation c-Met CARs containing an anti-c-Met singlechain variable fragment(scFv)as well as the CD28 signaling domain and CD3ζ(c-Met-28-3ζ),the CD137 signaling domain and CD3ζ(c-Met-137-3ζ),or the CD28 and CD137 signaling domains and CD3ζ(c-Met-28-137-3ζ)were constructed,and their abilities to target c-Met-positive HCC cells were evaluated in vitro and in vivo.All c-Met CARs were stably expressed on T cell membrane,and c-Met CAR-T cells aggregated around c-Met-positive HCC cells and specifically killed them in vitro.c-Met-28-137-3ζCAR-T cells secreted more interferon-gamma(IFN-γ)and interleukin 2(IL-2)than c-Met-28-3ζCAR-T cells and c-Met-137-3ζCAR-T cells.Compared with c-Met low-expressed cells,c-Met CAR-T cells secreted more cytokines when co-cultured with c-Met high-expressed cells.Moreover,c-Met-28-137-3ζCAR-T cells eradicated HCC more effectively in xenograft tumor models compared with the control groups.This study suggests that 3^(rd)-generation c-Met CAR-T cells are more effective in inhibiting c-Met-positive HCC cells than 2^(nd)-generation c-Met CAR-T cells,thereby providing a promising therapeutic intervention for c-Met-positive HCC.展开更多
Electrocatalytic N2 reduction to ammonia is a fascinating alternative to Haber-Bosch process and also considered as an energy sto rage method.This work,Fe doped MoS2/carbon cloth(CC) has been studied on the electro-ca...Electrocatalytic N2 reduction to ammonia is a fascinating alternative to Haber-Bosch process and also considered as an energy sto rage method.This work,Fe doped MoS2/carbon cloth(CC) has been studied on the electro-catalysis fix nitrogen indicating the doped Fe can indeed enhance the MoS2 material ability.Compared with MoS2/CC,Fe-Mo-S-3/CC not only increases 10 times in the rate of production ammonia,but also 5 times in Faraday efficiency.展开更多
Main observation and conclusion Inspired by the nitrogen fixation process on MoFe nitrogenase,asymmetrical coordinated Fe grafted onto 1T MoS_(2) were successfully synthesized.The unique electron-rich structure with a...Main observation and conclusion Inspired by the nitrogen fixation process on MoFe nitrogenase,asymmetrical coordinated Fe grafted onto 1T MoS_(2) were successfully synthesized.The unique electron-rich structure with asymmetrical coordination made the 1T Fe_(0.1)Mo_(0.9)S_(2) layered material actively react with water and dinitrogen at room temperature and atmosphere pressure.展开更多
This paper presents an imperfect maintenance strategy for the multi-component systems.The proposed maintenance strategy takes into account two types of maintenance actions,namely preventive maintenance(PM)and correcti...This paper presents an imperfect maintenance strategy for the multi-component systems.The proposed maintenance strategy takes into account two types of maintenance actions,namely preventive maintenance(PM)and corrective maintenance(CM).The imperfect effect of PM is modeled on the basis of the hybrid hazard rate model.Meanwhile,a new structure importance measure based on the survival signature is presented.Using this new importance measure method,an adjustment function is designed to update the PM maintenance threshold.For CM actions,a decision rule relying on the criticality level of components is introduced.In order to judge the criticality level of components,a novel structure updating method based on the survival signature is proposed.Moreover,a maintenance model considering economic dependence among components is developed.A 10-component system is finally introduced to illustrate the use and advantages of the proposed maintenance strategy.展开更多
基金grants from National Natural Science Foundation of China(81773268)Collaborative Innovation Center for Cancer Personalized Medicine,China(JX21817902/005).
文摘c-Met is a hepatocyte growth factor receptor overexpressed in many tumors such as hepatocellular carcinoma(HCC).Therefore,c-Met may serve as a promising target for HCC immunotherapy.Modifying T cells to express c-Met-specific chimeric antigen receptor(CAR)is an attractive strategy in treating c-Met-positive HCC.This study aimed to systematically evaluate the inhibitory effects of 2^(nd)-and 3^(rd)-generation c-Met CAR-T cells on hepatocellular carcinoma(HCC)cells.Here,2^(nd)-and 3^(rd)-generation c-Met CARs containing an anti-c-Met singlechain variable fragment(scFv)as well as the CD28 signaling domain and CD3ζ(c-Met-28-3ζ),the CD137 signaling domain and CD3ζ(c-Met-137-3ζ),or the CD28 and CD137 signaling domains and CD3ζ(c-Met-28-137-3ζ)were constructed,and their abilities to target c-Met-positive HCC cells were evaluated in vitro and in vivo.All c-Met CARs were stably expressed on T cell membrane,and c-Met CAR-T cells aggregated around c-Met-positive HCC cells and specifically killed them in vitro.c-Met-28-137-3ζCAR-T cells secreted more interferon-gamma(IFN-γ)and interleukin 2(IL-2)than c-Met-28-3ζCAR-T cells and c-Met-137-3ζCAR-T cells.Compared with c-Met low-expressed cells,c-Met CAR-T cells secreted more cytokines when co-cultured with c-Met high-expressed cells.Moreover,c-Met-28-137-3ζCAR-T cells eradicated HCC more effectively in xenograft tumor models compared with the control groups.This study suggests that 3^(rd)-generation c-Met CAR-T cells are more effective in inhibiting c-Met-positive HCC cells than 2^(nd)-generation c-Met CAR-T cells,thereby providing a promising therapeutic intervention for c-Met-positive HCC.
基金supported by Science and Technology Commission of Shanghai Municipality(Nos.17ZR1441200,18QA1402400 and 18230743400)National Natural Science Foundation of China(Nos.21771124,21901156)。
文摘Electrocatalytic N2 reduction to ammonia is a fascinating alternative to Haber-Bosch process and also considered as an energy sto rage method.This work,Fe doped MoS2/carbon cloth(CC) has been studied on the electro-catalysis fix nitrogen indicating the doped Fe can indeed enhance the MoS2 material ability.Compared with MoS2/CC,Fe-Mo-S-3/CC not only increases 10 times in the rate of production ammonia,but also 5 times in Faraday efficiency.
基金The work was supported by the Science and Technology Commission of National Natural Science Foundation of China(Nos.21901156,21975148 and 21771124)the Shanghai Municipality(Nos.19JC1412600,18QA1402400 and 18230743400)+4 种基金Z.Feng thanks the startup funding from Oregon State University.The XAS measurements were done at 9-BM of Advanced Photon Source,which is a U.S.Department of Energy(DOE)Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No.DE-AC02-06CH11357.T.Cheng and H.Yang thanks the Natural Science Foundation of Jiangsu Province(Grant No.SBK20190810)the Jiangsu Province High-Level Talents(JNHB-106)the China Postdoctoral Science Foundation(No.2019M660128)the Collaborative Innova-tion Center of Suzhou Nano Science&Technology,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the 111 Project.
文摘Main observation and conclusion Inspired by the nitrogen fixation process on MoFe nitrogenase,asymmetrical coordinated Fe grafted onto 1T MoS_(2) were successfully synthesized.The unique electron-rich structure with asymmetrical coordination made the 1T Fe_(0.1)Mo_(0.9)S_(2) layered material actively react with water and dinitrogen at room temperature and atmosphere pressure.
基金Supported by the Research Fund of Xijing University(XJ200204)the National Natural Science Foundation of China(11726623,11726624)the Natural Science Basic Research Plan in Shaanxi Province of China(2020JM-646,2021JQ-867)。
文摘This paper presents an imperfect maintenance strategy for the multi-component systems.The proposed maintenance strategy takes into account two types of maintenance actions,namely preventive maintenance(PM)and corrective maintenance(CM).The imperfect effect of PM is modeled on the basis of the hybrid hazard rate model.Meanwhile,a new structure importance measure based on the survival signature is presented.Using this new importance measure method,an adjustment function is designed to update the PM maintenance threshold.For CM actions,a decision rule relying on the criticality level of components is introduced.In order to judge the criticality level of components,a novel structure updating method based on the survival signature is proposed.Moreover,a maintenance model considering economic dependence among components is developed.A 10-component system is finally introduced to illustrate the use and advantages of the proposed maintenance strategy.
