Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how ...Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.展开更多
Developing stable but high active metal-nitrogen-carbon(M-N-C)-based hard carbon anode is a promising way to be the alternatives to graphene and blank hard carbon for sodium-ion batteries(SIBs),requiring the precise t...Developing stable but high active metal-nitrogen-carbon(M-N-C)-based hard carbon anode is a promising way to be the alternatives to graphene and blank hard carbon for sodium-ion batteries(SIBs),requiring the precise tailoring of the electronic structure for optimizing the Na+intercalation behavior,yet is greatly challenging.Herein,Fe-N-C graphitic layer-encapsulating Fe3C species within hard carbon nanosheets(Fe-N-C/Fe3C@HCNs)are rationally engineered by pyrolysis of self-assembled polymer.Impressively,the Fe-N-C/Fe3C@HCNs exhibit outstanding rate capacity(242 mAh·g^(−1)at 2,000 mA·g^(−1)),which is 2.1 and 4.2 times higher than that of Fe-N-C and N-doped carbon(N-C),respectively,and prolonged cycling stability(176 mAh·g^(−1)at 2,000 mA·g^(−1)after 2,000 cycles).Theoretical calculations unveil that the Fe3C species enhance the electronic transfer from Na to Fe-N-C,resulting in the charge redistribution between the interfaces of Fe3C and Fe-N-C.Thus,the optimized adsorption behavior towards Na+reduces the thermodynamic energy barriers.The synergistic effect of Fe3C and Fe-N-C species maintains the structural integrity of electrode materials during the sodiation/desodiation process.The in-depth insight into the advanced Na+storage mechanisms of Fe3C@Fe-N-C offers precise guidance for the rational establishment of confinement heterostructures in SIBs.展开更多
Dear Editor,X-linked sideroblastic anemia(XLSA),which is the most common genetic form of congenital sideroblastic anemia,is typically characterized by reduced heme synthesis and the presence of bone marrow(BM)ring sid...Dear Editor,X-linked sideroblastic anemia(XLSA),which is the most common genetic form of congenital sideroblastic anemia,is typically characterized by reduced heme synthesis and the presence of bone marrow(BM)ring sideroblasts containing pathologic iron deposits in the mitochondria.展开更多
基金funding from the National Science Foundation of China(31930016)the Peking-Tsinghua Center for Life Sciences+4 种基金ZW received funding from the State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases(2024KF00001)the National Science Foundation of China(82350119)CCW received funding from the Talent Introduction Funds from the Chinese Academy of Medical Science(2022-RC310-10)the National Science Foundation of China(32150005)the Research Funds from Health@InnoHK Program,launched by the Innovation Technology Commission of the Hong Kong Special Administrative Region.
文摘Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.
基金the National Key R&D Program of China(Nos.2016YFA0204100 and 2016YFA0200200)the National Natural Science Foundation of China(Nos.21890753,21988101,22162026,and 21875221)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB36030200)the Danish company Haldor Topsøe A/S,the Youth Talent Support Program of High-Level Talents Special Support Plan in Henan Province(No.ZYQR201810148)Creative talents in the Education Department of Henan Province(No.19HASTIT039).
文摘Developing stable but high active metal-nitrogen-carbon(M-N-C)-based hard carbon anode is a promising way to be the alternatives to graphene and blank hard carbon for sodium-ion batteries(SIBs),requiring the precise tailoring of the electronic structure for optimizing the Na+intercalation behavior,yet is greatly challenging.Herein,Fe-N-C graphitic layer-encapsulating Fe3C species within hard carbon nanosheets(Fe-N-C/Fe3C@HCNs)are rationally engineered by pyrolysis of self-assembled polymer.Impressively,the Fe-N-C/Fe3C@HCNs exhibit outstanding rate capacity(242 mAh·g^(−1)at 2,000 mA·g^(−1)),which is 2.1 and 4.2 times higher than that of Fe-N-C and N-doped carbon(N-C),respectively,and prolonged cycling stability(176 mAh·g^(−1)at 2,000 mA·g^(−1)after 2,000 cycles).Theoretical calculations unveil that the Fe3C species enhance the electronic transfer from Na to Fe-N-C,resulting in the charge redistribution between the interfaces of Fe3C and Fe-N-C.Thus,the optimized adsorption behavior towards Na+reduces the thermodynamic energy barriers.The synergistic effect of Fe3C and Fe-N-C species maintains the structural integrity of electrode materials during the sodiation/desodiation process.The in-depth insight into the advanced Na+storage mechanisms of Fe3C@Fe-N-C offers precise guidance for the rational establishment of confinement heterostructures in SIBs.
基金This work was supported by grants from the Ministry of Science and Technology of China(2019YFA0110803)the CAMS Innovation Fund for Medical Sciences(2016-I2M-1-002 and 2019-12M-1-006)the National Nature Science Foundation of China(81890992,81670112 and 81770175,82070201).
文摘Dear Editor,X-linked sideroblastic anemia(XLSA),which is the most common genetic form of congenital sideroblastic anemia,is typically characterized by reduced heme synthesis and the presence of bone marrow(BM)ring sideroblasts containing pathologic iron deposits in the mitochondria.
