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Id2 epigenetically controls CD8^(+)T-cell exhaustion by disrupting the assembly of the Tcf3-LSD1 complex

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Cellular & Molecular Immunology 2024年第3期21卷 292-308页

作者： Yiming Li Mingwei Han haolin Wei Wan Huang Zhinan Chen Tianjiao Zhang Meirui Qian Lin Jing Gang Nan Xiuxuan Sun Shuhui Dai Kun Wang Jianli jiang Ping Zhu Liang Chen Department of Cell Biology of National Translational Science Center for Molecular Medicine and Department of Clinical Immunology of Xijing Hospital Fourth Military Medical UniversityXi’anShaanxi 710032China State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases GanzhouJiangxi341000Xi’anShaanxi 710032China School of Medicine Shanghai UniversityShanghai 200444China

CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))subpopulations.Inhibitor of DNA binding protein 2(Id2)has been shown to play important roles in T-cell development and CD8^(+)T-cell immunity.However,the role of Id2 in CD8^(+)T-cell exhaustion is unclear.Here,we found that Id2 transcriptionally and epigenetically regulates the generation of Texprog cells and their conversion to Texterm cells.Genetic deletion of Id2 dampens CD8^(+)T-cell-mediated immune responses and the maintenance of stem-like CD8^(+)T-cell subpopulations,suppresses PD-1 blockade and increases tumor susceptibility.Mechanistically,through its HLH domain,Id2 binds and disrupts the assembly of the Tcf3-Tal1 transcriptional regulatory complex,and thus modulates chromatin accessibility at the Slamf6 promoter by preventing the interaction of Tcf3 with the histone lysine demethylase LSD1.Therefore,Id2 increases the abundance of the permissive H3K4me2 mark on the Tcf3-occupied E-boxes in the Slamf6 promoter,modulates chromatin accessibility at the Slamf6 promoter and epigenetically regulates the generation of Slamf6+Texprog cells.An LSD1 inhibitor GSK2879552 can rescue the Id2 knockout phenotype in tumor-bearing mice.Inhibition of LSD1 increases the abundance of Slamf6^(+)Tim-3^(−)Tex^(prog) cells in tumors and the expression level of Tcf1 in Id2-deleted CD8+T cells.This study demonstrates that Id2-mediated transcriptional and epigenetic modification drives hierarchical CD8^(+)T-cell exhaustion,and the mechanistic insights gained may have implications for therapeutic intervention with tumor immune evasion.

关键词： Id2 T-cell exhaustion Epigenetic modification Immune evasion

国家地震烈度速报江苏子系统震源机制解产出分析

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防灾减灾工程学报 2024年第3期44卷 730-734页

作者：杜航郑江蓉江昊琳王俊倪昊琦李子烨江苏省地震局江苏南京210014

国家地震烈度速报与预警系统江苏子系统震源机制解参数速报集成了TDMT_INV方法,可直接读取震相进行震源机制解反演计算并产出。为验证该方法获得震源机制解的准确性,选取2024年1月17日江苏东台3.0级地震和2023年12月7日江苏赣榆海域3.8... 详细信息

国家地震烈度速报与预警系统江苏子系统震源机制解参数速报集成了TDMT_INV方法,可直接读取震相进行震源机制解反演计算并产出。为验证该方法获得震源机制解的准确性,选取2024年1月17日江苏东台3.0级地震和2023年12月7日江苏赣榆海域3.8级地震这2次3级以上地震,采用TDMT_INV、CAP和FOCMEC方法计算其震源机制解,分析三种方法所得结果差异。东台3.0级地震位于江苏预警站网网内,三种方法都可获得较为稳定的震源机制解结果;赣榆海域3.8级地震位于江苏预警站网网外,TDMT_INV方法仍可获得较为稳定的震源机制解结果。

关键词：震源机制解 DMT_INV方法 CAP方法 FOCMEC方法

Metal-Free Synthesis of Benzo[a]phenanthridines from Aromatic Aldehydes,Cyclohexanones,and Aromatic Amines

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Chinese Journal of Chemistry 2022年第3期40卷 365-370页

作者： Pingyu jiang Zhifei Shan Shanping Chen Quanyuan Wang Shuxin jiang haolin zheng Guo-Jun Deng Key Laboratory for Green Organic Synthesis and Application of Hunan Province Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of EducationCollege of ChemistryXiongtan UniversityXiangtanHunon 411105China Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates(South China University of Technology) GuangzhouGuangdong 510640China

A three-component synthesis of benzo[a]phenanthridines from aromatic aldehydes,cyclohexanones,and aromatic amines has been developed,which is mediated by KI/DMSO/camphorsulfonic acid to afford a variety of functionalized benzo[a]phenanthridines in satisfactory yields.The present strategy provides a biaryl motif ortho to the nitrogen atom which has the potential to be used as ligand by further modification.With the advantages of readily available starting materials,transition-metal-free conditions,gram-scale synthesis,and broad substrate scope,this three-component protocol provides an efficient approach for the preparation of diverse benzo[a]phenanthridines.

关键词： Nitrogen heterocycles Multicomponent reactions Dehydroaromatization Cyclization Metal-free

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紧急救助制度的司法适用与理论反思

华北水利水电大学学报（社会科学版） 2024年第5期40卷 83-89页

作者：蒋永传陈浩林上海师范大学哲学与法政学院上海200234 北京航空航天大学法学院北京100191

《中华人民共和国民法典》第184条规定“紧急救助人不承担民事责任”制度,旨在鼓励见义勇为,遏制道德滑坡现象。然而,在司法实践中,该条款的适用出现了对“自愿”的识别标准不清晰、“紧急”的判断条件不明确、重大过失是否免责的认定... 详细信息

《中华人民共和国民法典》第184条规定“紧急救助人不承担民事责任”制度,旨在鼓励见义勇为,遏制道德滑坡现象。然而,在司法实践中,该条款的适用出现了对“自愿”的识别标准不清晰、“紧急”的判断条件不明确、重大过失是否免责的认定不一致等问题。从民法解释学的视角,该条款在司法适用中应当遵循以下规则:“自愿”无须与法定或约定义务相联系,直接根据文义进行认定,存在非因先行行为引起的法定义务或无偿约定义务时,也可适用该条款;“紧急”情形应当采用理性人标准判断且限于人身安全;救助人存在重大过失时应当减轻责任,而非完全豁免赔偿责任。

关键词：紧急救助不承担民事责任司法适用

Approximate CN scheme and its open region problems for metamaterial rotational symmetric simulation

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Journal of Systems Engineering and Electronics 2022年第6期33卷 1081-1087页

作者： WU Peiyu YU Han HU Yenan XIE Yongjun jiang haolin School of Electronic and Information Engineering Beihang UniversityBeijing 100191China Beijing Institute of Aerospace Systems Engineering Beijing 100076China School of Electronic&Information Engineering Nanjing University of Information Science and TechnologyNanjing 210096China

In order to simulate metamaterial rotational symmetric open region problems,unconditionally stable perfectly match layer(PML)implementation is proposed in the body of revolution(BOR)finite-difference time-domain(FDTD)lattice.More precisely,the proposed algorithm is implemented by the Crank-Nicolson(CN)Douglas-Gunn(DG)procedure for BOR metamaterial simulation.The constitutive relationship of metamaterial can be expressed by the Drude model and calculated by the piecewise linear recursive convolution(PLRC)approach.The effectiveness including absorption,efficiency,and accuracy is demonstrated through the numerical example.It can be concluded that the proposed implementation is to take the advantages of the CNDG-PML procedure,PLRC approach,and BORFDTD algorithm in terms of considerable accuracy,enhanced absorption and remarkable efficiency.Meanwhile,it can be demonstrated that the proposed scheme can maintain its unconditional stability when the time step exceeds the CourantFriedrichs-Levy(CFL)condition.

关键词： body of revolution(BOR) Crank-Nicolson(CN) finite-difference time-domain(FDTD) perfectly match layer(PML) metamaterial

In situ revealing the reconstruction behavior of monolayer rocksalt CoO nanosheet as water oxidation catalyst

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Journal of Energy Chemistry 2022年第7期31卷 373-381,I0010页

作者： Weiqi Guo haolin Luo Dongxu Fang Zhi jiang Jiasheng Chi Wenfeng Shangguan Research Center for Combustion and Environment Technology Shanghai Jiao Tong UniversityShanghai 200240China Center of Hydrogen Science Shanghai Jiao Tong UniversityShanghai 200240China

The reconstruction during oxygen evolution reaction (OER) significantly affects the electronic and local geometry structure of metal sites in electrocatalyst.Compared with well-investigated cobalt-based materials,the reconstruction of rocksalt CoO with purely Co^(2+) in octahedral (Oh) coordination has not been revealed in detail.Herein,monolayer Co O supported on reduced graphene oxide (r GO) was synthesized via a one-pot hydrothermal strategy with calcinating in Ar atmosphere.The structure evolution of twodimension (2D) Co O/r GO during OER was revealed by in situ X-ray absorption spectroscopy (XAS).The transition from Co O toward Co3O_(4) already occurred at open circuit potential,further enhanced at 1.23 V (vs.RHE).The Co Ox(OH)ywas determined as the active phase at 1.53 V,displaying a tetrahedral Co coordination defective spinel Co_(3)O_(4) with the Co-O shell that featured the (oxy)hydroxide,not the standard Co OOH.After OER,the irreversible transition from CoO to Co_(3)O_(4) was observed.In contrast,in situ Raman spectra revealed a reversible amorphization process on Co_(3)O_(4)/r GO under operation conditions.Furthermore,this study indicated that the reconstruction behavior could be more effectively revealed by XAS using 2D materials.

关键词： Oxygen evolution reaction Two-dimension materials Rocksalt CoO X-ray absorption spectroscopy In situ experiments

Iron-catalyzed indolo[2,3-c]quinoline synthesis from nitroarenes and benzylic alcohols/aldehydes promoted by elemental sulfur

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Green Synthesis and Catalysis

Green Synthesis and Catalysis 2022年第1期3卷 95-101页

作者： Rong Li Shuxin jiang haolin zheng Hanwen Lei Zhi Huang Shanping Chen Guo-Jun Deng Key Laboratory for Green Organic Synthesis and Application of Hunan Province Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of EducationCollege of ChemistryXiangtan UniversityXiangtan 411105China Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates(South China University of Technology) Guangzhou 510640China

An iron-catalyzed strategy for the rapid synthesis of indolo[2,3-c]quinolines has been developed.This cascade reaction involving alcohol oxidation,nitro reduction,and oxidative annulation was achieved in a one-pot.The present protocol was started from mono-functionalized indoles and readily available benzylic alcohols/aldehydes,affording a variety of functionalized indolo[2,3-c]quinolines in satisfactory yields.

关键词： Iron-catalyzed Nitro reduction Alcohol oxidation Oxidative annulation Indolo[2,3-c]quinolines

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猪圆环病毒2型相关疾病常见问题解析与对策

广东畜牧兽医科技 2024年第3期49卷 77-82页

作者：李彦超降浩琳白挨泉法国诗华动物保健公司北京100102 汝州市中等专业学校河南汝州467599 佛山科学技术学院广东佛山528051

PCV2是猪圆环病毒相关疾病的首要致病因子,会引起断奶仔猪多系统性衰竭综合征(PMWS)、繁殖障碍(PCV2-RD)以及猪皮炎肾病综合征(PDNS)等疾病,给养猪生产造成巨大的经济损失。该文从PCV2的流行特点、免疫存在问题以及对策等进行分析和讨论... 详细信息

PCV2是猪圆环病毒相关疾病的首要致病因子,会引起断奶仔猪多系统性衰竭综合征(PMWS)、繁殖障碍(PCV2-RD)以及猪皮炎肾病综合征(PDNS)等疾病,给养猪生产造成巨大的经济损失。该文从PCV2的流行特点、免疫存在问题以及对策等进行分析和讨论,旨在为养猪生产人员提供PCVD的防控思路。PCV2主要存在猪场流行率高、种猪群亚临床感染普遍、保育及育肥前期感染压力大、精液和初乳垂直传播等流行特点。种猪场的亚临床感染会引起仔猪PCV2的早期感染;保育及育肥前期感染压力大的主要原因是仔猪出现早期感染、母源抗体干扰、初乳摄入量不足、免疫抑制等;后备母猪的引种混乱和免疫驯化不到位,会导致后备母猪繁殖障碍及后代的早期感染;公猪精液受到PCV2的污染,会引起母猪的繁殖障碍,同时助推了PCV2在猪群中的流行。因此,对于PCVD的综合防控,需要从后备母猪、基础母猪、仔猪以及公猪出发,制订出适合猪场的免疫程序;配合减少交叉寄养、减低保育舍群体规模和密度、减少使用带毒精液、以及选择合适的消毒剂和消毒程序等管理措施,尽量减低PCV2带来的危害。

关键词： PCV2 流行特点免疫问题解析对策

A Frost Heaving Prediction Approach for Ground Uplift Simulation Due to Freeze-Sealing Pipe Roof Method

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Computer Modeling in Engineering & Sciences 2022年第7期131卷 251-266页

作者： Shengjun Deng haolin Chen Xiaonan Gong Jiajin Zhou Xiangdong Hu Gang jiang Institute of Geotechnical Engineering Nanjing Tech UniversityNanjing210009China Research Center of Coastal and Urban Geotechnical Engineering Zhejiang UniversityHangzhou310058China Department of Civil and Environmental Engineering Princeton UniversityPrincetonNJ08544USA Key Laboratory of Geotechnical and Engineering of Ministry of Education Department of Geotechnical EngineeringTongji UniversityShanghai200092China

Freeze-sealing pipe roof method is applied in the Gongbei tunnel,which causes the ground surface uplift induced by frost heave.A frost heaving prediction approach based on the coefficient of cold expansion is proposed to simulate the ground deformation of the Gongbei tunnel.The coefficient of cold expansion in the model and the frost heaving rate from the frost heave test under the hydration condition can achieve a good correspondence making the calculation result closer to the actual engineering.The ground surface uplift along the lateral and longitudinal direction are respectively analyzed and compared with the field measured data to validate the model.The results show that a good agreement between the frost heaving prediction model and the field measured data verifies the rationality and applicability of the proposed model.The maximum uplift of the Gongbei tunnel appears at the center of the model,gradually decreasing along with the lateral and longitudinal directions.The curve in the lateral direction presents a normal distribution due to the influence of the constraint of two sides,while the one along the lateral direction shapes like a parabola with the opening downward due to the temperature field distribution.The model provides a reference for frost heaving engineering calculation.

关键词： Freeze-sealing pipe roof method artificial ground freezing method tunnel construction frost heave temperature field