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scRNA-seq profiling of neonatal and adult thymus-derived CD4+ T cells by a T cell origin-time tracing model

Journal of Molecular Cell Biology 2022年第12期14卷 1-16页

作者： yuheng han Xinxing Ouyang Yao Chen Shujing Lai Hongxiang Sun Ningbo Wu Chun Ruan Limin Lu Bing Su Shanghai Institute of Immunology Department of Immunology and Microbiologyand the Ministry of Education Key Laboratory of Cell Death and DifferentiationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Tumor Biology Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Center for Human Translational Immunology at Shanghai Institute of Immunology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Jiao Tong University School of Medicine–Yale Institute for Immune Metabolism Shanghai Jiao Tong University School of MedicineShanghai 200025China Key Laboratory of Molecular Radiation Oncology of Hunan Province Xiangya HospitalCentral South UniversityChangsha 410008China

It is well documented that the neonatal thymus-derived (neonatal-TD) regulatory T cells (Treg) are essential to prevent lethal autoimmune diseases and allergies, and neonatal and adult thymus possesses distinct output potentials for naïve T cells, including Treg. However, the molecular features and detailed functional differences between neonatal-TD and adult thymus-derived (adult-TD) T cells in terms of their ability to maintain immune homeostasis during long-term environmental influences are still largely unknown, partially due to the lack of appropriate animal models to precisely trace these cells at specific time points. In this study, neonatal-TD and adult-TD CD4+ T cells from the spleen and Peyer's patches were traced for 9 weeks by a T cell origin-time tracing mouse model and analysed by single-cell RNA sequencing. More Treg but fewer naïve T cells were found in neonatal-TD CD4+ T cells from both tissues than those from adult-TD counterparts. Interestingly, the neonatal-TD Treg in both the spleen and Peyer's patches exhibited augmented expression of Foxp3, Gata3, Ctla4, Icos, Il2ra, Tgfb1, and Nrp1, as well as enriched Gene Ontology terms like T cell activation and tolerance induction, indicating an enhanced immunosuppressive function. These results were further confirmed by flow cytometry analysis and in vitro immune suppression assays. Flow cytometry also revealed a significantly higher proportion of neonatal-TD Treg in total Treg than that of adult-TD counterparts, suggesting the longer lifespan of neonatal-TD Treg. To investigate the intrinsic features of neonatal-TD and adult-TD CD4+ T cells, a shortened tracing time was performed. Surprisingly, the neonatal-TD and adult-TD CD4+ T cells had similar proportions of Treg and did not exhibit significant differences in Foxp3, Gata3, Ctla4, Icos, Il2ra, and Tgfb1 expression levels after tracing for 12 days. On the other hand, neonatal-TD Treg present an increased Nrp1 expression level compared with adult-TD co

关键词： T lineage tracing Treg neonatal thymus-derived T cells neonatal thymus-derived Treg single-cell RNA sequencing

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Electron-electron interactions in monolayer graphene quantum capacitors

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Nano Research 2013年第8期6卷 619-626页

作者： Xiaolong Chen Lin Wang Wei Li Yang Wang Zefei Wu Mingwei Zhang Yu han yuheng He Ning Wang Department of Physics and the William Mong Institute of Nano Science and Technology Hong Kong University of Science andTechnology Hong Kong S.A.R. China

We demonstrate the effects of electron-electron （e-e） interactions in monolayer graphene quantum capacitors. Ultrathin yttrium oxide showed excellent per-formance as the dielectric layer in top-gate device geometry. The structure and dielectric constant of the yttrium oxide layers have been carefully studied. The inverse compressibility retrieved from the quantum capacitance agreed fairly well with the theoretical predictions for the e--e interactions in monolayer graphene at different temperatures. We found that electron-hole puddles played a significant role in the low-density carrier region in graphene. By considering the temperature-dependent charge fluctuation, we established a model to explain the round-off effect originating from the e-e interactions in monolayer graphene near the Dirac point.

关键词： graphene e-e interaction inverse compressibility quantum capacitance charge fluctuation electron-hole puddles

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Regulation of CD8^(+)T memory and exhaustion by the mTOR signals

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Cellular & Molecular Immunology 2023年第9期20卷 1023-1039页

作者： Yao Chen Ziyang Xu Hongxiang Sun Xinxing Ouyang yuheng han Haihui Yu Ningbo Wu Yiting Xie Bing Su Shanghai Institute of Immunology Department of Immunology and Microbiologyand The Ministry of Education Key Laboratory of Cell Death and DifferentiationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Tumor Biology Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Center for Immune-Related Diseases at Shanghai Institute of Immunology Department of GastroenterologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Jiao Tong University School of Medicine–Yale Institute for Immune Metabolism Shanghai Jiao Tong University School of MedicineShanghaiChina Key Laboratory of Molecular Radiation Oncology of Hunan Province Xiangya HospitalCentral South UniversityChangshaChina

CD8^(+)T cells are the key executioners of the adaptive immune arm,which mediates antitumor and antiviral ***ïve CD8^(+)T cells develop in the thymus and are quickly activated in the periphery after encountering a cognate antigen,which induces these cells to proliferate and differentiate into effector cells that fight the initial ***,a fraction of these cells become long-lived memory CD8^(+)T cells that combat future ***,the generation and maintenance of memory cells is profoundly affected by various in vivo conditions,such as the mode of primary activation(e.g.,acute *** immunization)or fluctuations in host metabolic,inflammatory,or aging ***,many T cells may be lost or become exhausted and no longer *** intracellular signaling pathways,transcription factors,epigenetic modifications,and metabolic processes are involved in this ***,understanding the cellular and molecular basis for the generation and fate of memory and exhausted CD8^(+)cells is central for harnessing cellular *** this review,we focus on mammalian target of rapamycin(mTOR),particularly signaling mediated by mTOR complex(mTORC)2 in memory and exhausted CD8^(+)T cells at the molecular level.

关键词： mTOR Sin1 CD8^(+)T cell T-cell memory T-cell exhaustion

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Metabolic regulation of T cell development by Sinl-mTORC2 is mediated by pyruvate kinase M2

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Journal of Molecular Cell Biology 2019年第2期11卷 93-106页

作者： Xinxing Ouyang yuheng han Guojun Qu Man Li Ningbo Wu Hongzhi Liu Omotooke Arojo Hongxiang Sun Xiaobo Liu Dou Liu Lei Chen Qiang Zou Bing Su Shanghai Institute of Immunology Department of Immunology and Microbiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Immunobiology and the Vascular Biology and Therapeutics Program Yale University School of Medicine 333 Cedar Street New Haven CT 06520 USA

Glucose metabolism plays a key role in thymocyte development. The mammalian target of rapamycin complex 2 (mT0RC2) is a critical regulator of cell growth and metabolism, but its role in early thymocyte development and metabolism has not been fully studied. We show here that genetic ablation of Sinl, an essential component of mTORC2, in T lineage cells results in severely impaired thymocyte development at the CD4^- CD8^- double negative (DN) stages but not at the CD4^+ CD8^+ double positive (DP) or later stages. Notably, Sinl-deficient DN thymocytes show markedly reduced proliferation and ***, we discover that the M2 isoform of pyruvate kinase (PKM2) is a novel and crucial Sinl effector in promoting DN thymocyte development and metabolism. At the molecular level, we show that Sinl-mTORC2 controls PKM2 expression through an AKT-dependent PPAR-y nuclear translocation. Together, our study unravels a novel mTORC2-PPAR-γ-PKM2 pathway in immune-metabolic regulation of early thymocyte development.

关键词： mT0RC2 Sinl thymocyte development PPAR-γ PKM2 metabolism

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MAP3K2 augments Th1 cell differentiation via IL-18 to promote T cell-mediated colitis

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Science China(Life Sciences) 2021年第3期64卷 389-403页

作者： Ningbo Wu Dongping Chen Hongxiang Sun Jianmei Tan Yao Zhang Tianyu Zhang yuheng han Hongzhi Liu Xinxing Ouyang Xiao-Dong Yang Xiaoyin Niu Jie Zhong Zhengting Wang Bing Su Shanghai Institute of Immunology Department of Immunology and Microbiologyand Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai JiaoTong University School of MedicineShanghai 200025China Shanghai JiaoTong University School of Medicine-Yale Institute for Immune Metabolism Shanghai JiaoTong University School of MedicineShanghai 200025China Department of Gastroenterology Ruijin HospitalShanghai JiaoTong University School of MedicineShanghai 200025China

T cell-mediated immunity in the intestine is stringently controlled to ensure proper immunity against pathogenic microbes and to prevent autoimmunity,a known cause of inflammatory bowel ***,precisely how T cells regulate intestine immunity remains to be fully *** this study,we found that mitogen-activated protein kinase kinase kinase 2(MAP3K2)is required for the CD4^(+)T cell-mediated inflammation in the *** a T cell transfer colitis model,we found that MAP3K2-deficient naïve CD4^(+)T cells had a dramatically reduced ability to induce colitis compared to wild type T *** addition,significantly fewer IFN-γ-but more IL-17A-producing CD4^(+)T cells in the intestines of mice receiving MAP3K2-deficient T cells than in those from mice receiving wild type T cells was ***,under well-defined in vitro differentiation conditions,MAP3K2-deficient naïve T cells were not impaired in their ability to differentiate into Th1,Th17 and ***,the MAP3K2-regulated colitis severity was mediated by Th1 but not Th17 cells in the *** the molecular level,we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK ***,our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.

关键词： MAP3K2 IL-18 Th1 T cell immunity colitis

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Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc

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Cellular & Molecular Immunology 2019年第9期16卷 757-769页

作者： Man Li Adam S.Lazorchak Xinxing Ouyang Huihui Zhang Hongzhi Liu Omotooke A.Arojo Lichong Yan Jingsi Jin yuheng han Guojun Qu Yuhong Fu Xiaocao Xu Xiaobo Liu Wenqian Zhang Zhengfeng Yang Chuan Ruan Qijun Wang Dou Liu Chuanxin Huang Lu Lu Shibo Jiang Fubin Li Bing Su Shanghai Institute of Immunology Department of Immunology and MicrobiologyKey Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Immunobiology and the Vascular Biology and Therapeutics Program Yale University School of Medicine333 Cedar StreetNew HavenConnecticut 06520USA Present address:EMD Serono Research&Development Institute Inc.45 Middlesex TpkeBillericaMA 01821–3936USA Hongqiao International Institute of Medicine Shanghai Tongren Hospital and Faculty of Basic MedicineShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Public Health Clinical Center and School of Basic Medical Sciences Key Laboratory of Medical Molecular Virology of MOE/MOHFudan UniversityShanghaiChina

Proper control of B cell growth and metabolism is crucial for B-cell-mediated immunity,but the underlying molecular mechanisms remain incompletely *** this study,Sin1,a key component of mTOR complex 2(mTORC2),specifically regulates B cell growth and *** ablation of Sin1 in B cells reduces the cell size at either the transitional stage or upon antigen stimulation and severely impairs ***1 deficiency also severely impairs B-cell proliferation,antibody responses,and anti-viral *** the molecular level,Sin1 controls the expression and stability of the c-Myc protein and maintains the activity of mTORC1 through the Akt-dependent inactivation of GSK3 and TSC1/2,***,our study reveals a novel and specific role for Sin1 in coordinating the activation of mTORC2 and mTORC1 to control B cell growth and metabolism.

关键词： metabolism immunity stimulation

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基于LSTM神经网络的轨道预报算法研究

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科学技术创新 2022年第21期 88-91页

作者：韩雨恒中南大学航空航天学院湖南长沙410083

传统的轨道预报方法,主要分为数值法和解析法,数值法计算精度高但计算速度慢,星载计算机的算力要求很高;解析法计算精度低但计算速度快,对星载计算机的算力要求较低。随着卫星技术的发展,卫星的自主定轨和智能化变得越来越重要,而传统... 详细信息

传统的轨道预报方法,主要分为数值法和解析法,数值法计算精度高但计算速度慢,星载计算机的算力要求很高;解析法计算精度低但计算速度快,对星载计算机的算力要求较低。随着卫星技术的发展,卫星的自主定轨和智能化变得越来越重要,而传统的轨道预报方法不能很好的满足这一要求,即兼顾计算精度和计算速度。针对这一问题,提出一种基于LSTM神经网络的轨道预报算法,该方法通过使用LSTM神经网络对解析法的预测值与卫星的真实位置的误差进行训练,从而来预测解析法在未来时刻的预报误差,通过对误差的修正来提高预测的准确性,且具有较快的计算速度。

关键词：轨道预报神经网络 LSTM神经网络

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基于碳排放系数法对不同装配率的装配式建筑碳排放测算与分析

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建筑结构 2023年第S1期53卷 1337-1342页

作者：韩宇恒于哲陈滕中国建筑设计研究院有限公司北京100044

自2020年9月22日习近平总书记在75届联合国气候大会上承诺:中国二氧化碳排放力争于2030年达到峰值,努力争取2060年前实现碳中和。随后各省相继启动编制对应的“碳达峰”和“碳中和”计划并如火如荼的开展。资料显示,碳排放量与经济增长... 详细信息

自2020年9月22日习近平总书记在75届联合国气候大会上承诺:中国二氧化碳排放力争于2030年达到峰值,努力争取2060年前实现碳中和。随后各省相继启动编制对应的“碳达峰”和“碳中和”计划并如火如荼的开展。资料显示,碳排放量与经济增长呈现出同步变化趋势。随着我国经济的告诉发展,碳排放量也逐渐增大至世界首位。政府主导的减排政策的出台与实施,在减碳方面取得了显著的成效。目前还未碳达峰,但增速放缓。建筑行业作为排碳龙头,大力开展绿色环保的装配式技术是一条可行之路。为了研究装配式建筑排碳特点和痛点,通过碳排放系数法对不同装配率的装配式建筑碳排放量进行模拟测算。不仅得到了物化阶段建筑碳排放量,也总结出碳排放量随装配率的升高而降低的客观规律,为促进装配式建筑的推广发展提供了理论依据。

关键词：装配式建筑装配率碳排放碳排放系数法碳因子

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苯抽提装置火炬管线冻堵原因分析及处理措施

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安全、健康和环境 2009年第10期9卷 5-6页

作者：翟鹏韩玉恒中国石化中原石油化工有限责任公司河南濮阳457000

中国石化中原石油化工有限责任公司（以下简称中原乙烯）为拉长产业链，2004年7月建成苯抽提装置，采用石油化工科学研究院开发的环丁砜抽提蒸馏分离苯专利技术，设计处理裂解加氢汽油10×10^4t／a，生产纯苯5．1×10^4t／a。自投产以... 详细信息

中国石化中原石油化工有限责任公司（以下简称中原乙烯）为拉长产业链，2004年7月建成苯抽提装置，采用石油化工科学研究院开发的环丁砜抽提蒸馏分离苯专利技术，设计处理裂解加氢汽油10×10^4t／a，生产纯苯5．1×10^4t／a。自投产以来，因苯检验罐、抽提蒸馏塔、密闭式取样器等主要设备排放火炬管线设计不合理，火炬管网不断出现波动，严重影响了苯抽提装置的平稳操作，经过对产生火炬管网波动原因的分析，并采取相应技术改造措施，恢复了苯抽提装置平稳操作。

关键词：苯抽提装置火炬管线冻堵原因分析处理措施

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苯抽提装置火炬管线冻堵的原因及解决措施

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石油化工安全环保技术 2009年第1期25卷 35-36,46页

作者：翟鹏韩玉恒中原石油化工有限责任公司河南濮阳457000

介绍苯抽提装置火炬管线的设计思路,列出生产中存在的问题,对问题进行了原因分析,通过采取措施,解决了火炬管线冻堵的问题。

关键词：苯火炬管线冻堵原因解决措施

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