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Structural understanding of T cell receptor triggering

Cellular & Molecular Immunology 2020年第3期17卷 193-202页

作者： Xinyi Xu Hua Li Chenqi Xu State Key Laboratory of Molecular Biology Shanghai Science Research CenterCAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of Sciences320 Yueyang Road200031 ShanghaiChina School of Life Science and Technology ShanghaiTech University100 Haike Road201210 ShanghaiChina

The T cell receptor(TCR)is one of the most complicated receptors in mammalian cells,and its triggering mechanism remains *** an octamer complex,TCR comprises an antigen-binding subunit(TCRαβ)and three CD3 signaling subunits(CD3ζζ,CD3δε,and CD3γε).Engagement of TCRαβwith an antigen peptide presented on the MHC leads to tyrosine phosphorylation of the immunoreceptor tyrosine-based activation motif(ITAM)in CD3 cytoplasmic domains(CDs),thus translating extracellular binding kinetics to intracellular signaling *** conformational change plays an important role in the transmembrane signal transduction of TCR is under *** by the complexity and functional importance of TCR,many groups have been studying TCR structure and triggering for decades using diverse biochemical and biophysical ***,we synthesize these structural studies and discuss the relevance of the conformational change model in TCR triggering.

关键词： T Cell Receptor Structure Conformational change Triggering

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Two-dimensional Health State Map to define metabolic health using separated static and dynamic homeostasis features: a proof-of-concept study

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National science Review 2025年第1期 54-68页

作者： Yanpu Wu Xinyan Zhang Liang Sun Qingqing Wu Xiaoping Liu Yueyi Deng Zhenzhen Lu Zhongxia Li Chaoming Deng Ruikun He Luyun Zhang Rong Zeng Xuguang Zhang Luonan Chen Xu Lin Shanghai Institute of Nutrition and Health Chinese Academy of Sciences BYHEALTH Institute of Nutrition & Health Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Key Laboratory of Systems Biology Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences Department of Nutrition and Food Hygiene School of Public Health Institute of Nutrition Fudan University Department of Nephrology Longhua Hospital Shanghai University of Traditional Chinese Medicine School of Life Science and Technology Shanghai Tech University

Defining metabolic health is critical for the earlier reversing of metabolic dysfunction and disease, and fasting-based diagnosis may not adequately assess an individual's metabolic adaptivity under stress. We constructed a novel Health State Map(HSM) comprising a Health Phenotype Score(HPS) with fasting features alone and a Homeostatic Resilience Score(HRS) with five time-point features only(t = 30, 60, 90,180, 240 min) following a standardized mixed macronutrient tolerance test(MMTT). Among 111 Chinese adults, when the same set of fasting and post-MMTT data as for the HSM was used, the mixed-score was highly correlated with the HPS. The HRS was significantly associated with metabolic syndrome prevalence,independently of the HPS(OR [95% CI]: 0.41 [0.18, 0.92]) and the mixed-score(0.34 [0.15, 0.69]).Moreover, the HRS could discriminate metabolic characteristics unseparated by the HPS and the mixed-score. Participants with higher HRSs had better metabolic traits than those with lower HRSs. Large interpersonal variations were also evidenced by evaluating postprandial homeostatic resiliencies for glucose,lipids and amino acids when participants had similar overall HRSs. Additionally, the HRS was positively associated with physical activity level and specific gut microbiome structure. Collectively, our HSM model might offer a novel approach to precisely define an individual's metabolic health and nutritional capacity.

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Epigenetic regulation of cardiac tissue development by lysine lactylation

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hlife 2025年第2期3卷 82-97页

作者： Xiaodong Luan Runhua Du Gengchen Su Cong Yan Xuelian Ren Kaide Ju Ye Jin Yang An Dan Guo Zhuang Tian He Huang Shuyang Zhang Center for Drug Research and Evaluation Institute of Clinical MedicinePeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijingChina Department of Rare Diseases Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical ScienceBeijingChina State Key Laboratory of Chemical Biology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesZhejiangChina School of Medicine Tsinghua UniversityBeijingChina Tsinghua-Peking Center for Life Sciences Tsinghua UniversityBeijingChina Department of Cardiology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijingChina GemPharmatech Co. Ltd.JiangsuChina

Heart disease stands as the foremost global cause of *** rodents,the heart possesses the remarkable ability for cardiac regeneration within the first 7 days ***,the transition to an oxygen-rich environment and altered nutrient availability trigger a profound shift in cardiac energy metabolism immediately after ***,which translates metabolic adjustments into enduring gene expression patterns,has been recognized for its role in this ***,its role in heart development has remained *** this study,we conduct an integrated study combining global proteomics,lactylome,and genome-wide RNA sequencing to elucidate the role of lactylation throughout postnatal heart *** findings demonstrate a remarkable increase in non-histone lactylation levels as early as 1 week(1 w)to 6 weeks(6 w)postpartum and remained elevated from 6 months(6 m)***,the histone lactylation showed the opposite ***,we propose that histone 4 lysine 12 lactylation(H4K12la)acts as a pivotal upstream regulatory element in the early postnatal mouse heart,from 1 w to 6 w *** findings strongly suggest a significant connection between lactylation and postnatal cardiac development and highlight its involvement in gene expression regulation,thus offering potential mechanisms for targeting heart diseases.

关键词： cardiac tissue development multi-omics analysis H4K12la gene expression regulation

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Characterization of tree shrew telomeres and telomerase

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Journal of Genetics and Genomics 2021年第7期48卷 631-639页

作者： Jian Sun Wenjing Liu Yongbo Guo Hailin Zhang Dewei Jiang Ying Luo Rong Liu Ceshi Chen Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences&Yunnan Province National Resource Center for Non-Human PrimatesKunming Primate Research CenterNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyKunmingYunnan 650201China Kunming College of Life Sciences University of Chinese Academy SciencesKunmingYunnan 650204China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Laboratory of Molecular Genetics of Aging&Tumor Medical FacultyKunming University of Science and TechnologyKunmingYunnan 650500China

The use of tree shrews as experimental animals for biomedical research is a new *** recent studies suggest that tree shrews are suitable for studying cancers,including breast cancer,glioblastoma,lung cancer,and hepatocellular ***,the telomeres and the telomerase of tree shrews have not been studied to ***,we characterize telomeres and telomerase in tree *** telomere length of tree shrews is approximately 23 kb,which is longer than that of primates and shorter than that of mice,and it is extended in breast tumor tissues according to Southern blot and flow-fluorescence in situ hybridization(FISH)*** shrew spleen,bone marrow,testis,ovary,and uterus show high telomerase activities,which are increased in breast tumor tissues by telomeric repeat amplification protocol *** telomere length becomes shorter,and telomerase activity decreases with *** tree shrew TERT and TERC are more highly similar to primates than to *** findings lay a solid foundation for using tree shrews to study aging and cancers.

关键词： Tree shrews Telomere TERT TERC Breast cancer

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Toxoplasma TgCtwh3 Δ rop16 Ⅰ/Ⅲ accelerates neuronal apoptosis and APP production in mouse with acute infection

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IBRO Neuroscience Reports 2025年 18卷 830-843页

作者： Di Yang Cong Wang Qing Tao Lei Liu Mengmeng Jin Haiping Cai Meijuan Zheng Mengtao Gong Li Yu Jian Du Qingli Luo Jilong Shen Kunpeng Qin Deyong Chu Department of Pathogen Biology Anhui Province Key Laboratory of Microbiology & Parasitology Anhui Provincial Laboratory of Zoonoses of High Institutions School of Basic Medicine Anhui Medical University Hefei China Department of Orthopaedics The First Affiliated Hospital of Anhui Medical University. Anhui Public Health Clinical Center Hefei China Department of Laboratory Medicine Affiliated Drum Tower Hospital Nanjing University School of Medicine Nanjing China Department of Blood Transfusion the First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei China Maternity and Child Health Hospital of Anhui Province the Affiliated Maternity and Child Health Hospital of Anhui Medical University Hefei China Spine center Department of Orthopaedics The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei China Department of Laboratory Medicine the First Affiliated Hospital of Anhui Medical University Hefei China Department of Microbiology and Parasitology Anhui Provincial Laboratory of Microbiology and Parasitology Anhui Provincial Laboratory of Zoonoses of High Institutions School of Basic Medical Sciences Anhui Medical University Hefei China Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Anhui Medical University Hefei China

Objective To explore the mechanism by which rop16 Ⅰ/Ⅲ -deficient/ gra15 Ⅱ -dominant toxoplasma gondii Chinese 1 genotype Wh3 (TgCtwh3 Δ rop16 Ⅰ/Ⅲ ) strain induced neuron apoptosis, APP and BACE1 production in vivo and vitro . Method BALB/c mice were infected by intraperitoneal injection with TgCtwh3 wild type (TgCtwh3 WT) and TgCtwh3 Δ rop16 Ⅰ/Ⅲ tachyzoites, respectively. One week after infection, the morphology and number of hippocampal neurons were examined by hematoxylin-eosin (H&E) and Nissl staining. Expression levels of apoptosis-related proteins, APP, BACE1 as well as inflammatory factors proteins and genes in the hippocampus were evaluated using western blotting and qRT-PCR. The hippocampal neuron cell line HT22 was infected with TgCtwh3 WT and TgCtwh3 Δ rop16 Ⅰ/Ⅲ tachyzoite, respectively, and the expression of target proteins was analyzed through immunofluorescence staining and western blotting. Furthermore, HT22 apoptosis was assessed using flow cytometry. Result BALB/c mice injected with TgCtwh3 Δ rop16 Ⅰ/Ⅲ tachyzoites presented abnormal appearance and posture changes as well as declined vitality. The hippocampus assay demonstrated that TgCtwh3 Δ rop16 Ⅰ/Ⅲ toxoplasma caused neuron loss, neuron alignment disorder, neuronal nucleus abnormal deep-stained and neuron apoptosis. Furthermore, TgCtwh3 Δ rop16 Ⅰ/Ⅲ tachyzoites caused obvious production of APP, BACE1and expression increase of pro-inflammatory factors in hippocampal tissue compared to these in mice infected with TgCtwh3 WT tachyzoites. Contrarily, the expression of transforming growth factor beta 1 (TGF-β1), a pivotal anti-inflammatory cytokine was significantly decreased in TgCtwh3 Δ rop16 Ⅰ/Ⅲ infected mice. Further study showed that TgCtwh3 Δ rop16 Ⅰ/Ⅲ tachyzoites induced HT22 apoptosis through triggering ERS, meanwhile promoted HT22 to produce APP, BACE1 by activating NF-κB signaling pathway. Conclusion Our results indicated that the GRA15 Ⅱ effector may play a crucial part in neuron apoptosis, pr

关键词： T.gondii Chinese 1 genotype Wh3 strain ROP16 Ⅰ/Ⅲ Hippocampal neuron Apoptosis APP

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Spatiotemporal Distribution of Microplastics in the Ganjiang River (Ganzhou Section): Insight into the Source Area Impact

SSRN

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SSRN 2022年

作者： Qin, Xinxin Sun, Nan Teng, Wenxi Zhu, Yichun Liu, Zuwen Li, Wentao Dong, Huiyu Qiang, Zhimin Zeng, Jinfeng Lian, Junfeng Jiangxi Provincial Key Laboratory of Environmental Geotechnology and Engineering Disaster Control Jiangxi University of Science and Technology 1958 Ke-jia Road Ganzhou341000 China Ganzhou Key Laboratory of Basin Pollution Simulation and Control Jiangxi University of Science and Technology 1958 Ke-jia Road Ganzhou341000 China School of Life Sciences Jinggangshan University Ji’an343009 China Key Laboratory of Drinking Water Science and Technology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences 18 Shuang-qing Road Beijing100085 China Hydrology and Water Resources Monitoring Center for Ganjiang Upstream Watershed 8 Zhang-jia-wei Road Ganzhou341000 China

The accumulation of microplastic (MP) pollution in rivers has become a global concern;however, the underlying mechanism for spatiotemporal effects on MPs remains unclear. This study investigated the Ganjiang River source area with a field survey and found relatively low MP abundances in the target rivers (3.47 ± 0.95 items/L) owing to the small background in the riverine source area. The average MP abundance in the dry season (10.9 ± 2.33 items/L) was higher than that in the middle wet season (3.47 ± 0.95 items/L), and small MPs were prone to scouring from land. Within the predominant MP shape (fiber and fragment), size (0.125–0.5 mm), and colour (polychrome and white) distribution, the contribution of functional areas was as follows: industrial > scenic > residential > natural area. MP abundances fluctuated with different rainfall levels in the wet season, while during the period when the river flow was manually regulated, a good linear relationship was observed between river flow and MP abundance, suggesting that land scouring and transportation may play a more important role than other factors. The upper river regions predominated in the group in which the average MP abundance in the dry season was higher than that in the wet season. The small watershed area in the upstream region would lead to a low terrestrial MP number, making it easy for MP content in rivers to reach a platform. This work contributes to the understanding of MP distribution in freshwater and provides a potential guideline for MP control. © 2022, The Authors. All rights reserved.

关键词： Microplastic

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Solvent-Free Conjugated Polymer Fluids with Optical Functions

Organic Materials

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Organic Materials 2021年第2期3卷 309-320页

作者： Shinohara, Akira Guo, Zhenfeng Pan, Chengjun Nakanishi, Takashi Shenzhen Key Laboratory of Polymer Science and Technology College of Materials Science and Engineering Shenzhen University 1066 Xueyuan Boulevard Nanshan Shenzhen 518055 China Division of Soft Matter Graduate School of Life Science Hokkaido University Kita 10 Nishi 8 Kita-ku Sapporo 060-0810 Japan International Center for Materials Nanoarchitectonics (WPI-MANA) National Institute for Materials Science (NIMS) 1-1 Namiki Tsukuba 305-0044 Japan

Solvent-free fluidic materials possessing optoelectronic functions are expected to be major components in soft electronics applications. Conjugated polymers are promising targets for this purpose and their design approaches are classified into three types with respect to their structure: conjugation breaking (Type I), copolymerization with flexible polymers (Type II), and side chain engineering (Type III). In this short review, we highlight several early attempts to produce Type III conjugated *** also present fully characterized Type III fluids recently developed by our group, with a brief summary of the structure property relationship and fluidity-oriented functions. © 2021. The Author(s).

关键词： conjugated polymers rheology solvent-free fluids viscoelasticity

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Activation of AMPKα1 is essential for regulatory T cell function and autoimmune liver disease prevention

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Cellular & Molecular Immunology 2021年第12期18卷 2609-2617页

作者： Huaiping Zhu Zhaoyu Li Junqing An Miao Zhang Yu Qiu Ming-Hui Zou The First Affiliated Hospital of USTC Anhui Provincial Key Laboratory of Blood Research and ApplicationsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui230001P.R.China Center for Molecular and Translational Medicine Georgia State UniversityAtlantaGA30303USA Medical Research Center Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong510120P.R.China Department of Medicine University of Oklahoma Health Sciences CenterOklahoma CityOK73117USA

Regulatory T cells(Treg cells)are crucial for maintaining immune *** the regulatory function of Treg cells can lead to autoimmune liver ***,how Treg cell function is regulated has not been fully ***,we report that mice with AMP-activated protein kinase alpha 1(AMPKα1)globally knocked out spontaneously develop immune-mediated liver injury,with massive lymphocyte infiltration in the liver,elevated serum alanine aminotransferase levels,and greater production of *** transplantation of wild-type bone marrow and adoptive transfer of wild-type Treg cells can prevent liver injury in AMPKα1-KO *** addition,Treg cell-specific AMPKα1-KO mice display histological features similar to those associated with autoimmune liver disease,greater production of autoantibodies,and hyperactivation of CD4^(+)T ***α1 deficiency significantly impairs Treg cell suppressive function but does not affect Treg cell differentiation or ***,AMPK is activated upon T cell receptor(TCR)stimulation,which triggers Foxp3 phosphorylation,suppressing Foxp3 ubiquitination and proteasomal ***,the frequency of Treg cells and the phosphorylation levels of AMPK at T172 in circulating blood are significantly lower in patients with autoimmune liver ***:Our data suggest that AMPK maintains the immunosuppressive function of Treg cells and confers protection against autoimmune liver disease.

关键词： AMPK Treg cells autoimmune liver diseases Foxp3

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A Dual-Responsive Electrochemical Biosensor Based on Artificial Protein Imprinted Polymers and Natural Hyaluronic Acid for Sensitive Recognition Towards Biomarker Cd44

SSRN

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SSRN 2022年

作者： Cui, Min Sun, Xiaofeng Liu, Rui Du, Meigui Song, Xiaoming Wang, Shuai Hu, Wei Luo, Xiliang Shandong Provincial Key Laboratory of Molecular Engineering School of Chemistry and Chemical Engineering Qilu University of Technology Shandong Academy of Sciences Jinan250353 China The Affiliated Qingdao Central Hospital of Qingdao University The Second Affiliated Hospital of Medical College of Qingdao University Qingdao266042 China Medical Products Co. Ltd. Weihai264200 China Jinan250353 China Qingdao University of Science and Technology Qingdao266042 China Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science MOE Shandong Key Laboratory of Biochemical Analysis College of Chemistry and Molecular Engineering Qingdao University of Science and Technology Qingdao266042 China

Two main challenges for biosensors are analytical sensitivity and selectivity. Ultra-highly specific protein molecularly imprinted polymers (MIPs) with characteristics of easy preparation, chemical stability, convenient assembly with transducer, offer unprecedented opportunities for high-performance recognition towards targets. A dual-responsive electrochemical biosensor was demonstrated, where integrated both artificial protein MIPs and natural hyaluronic acid (HA) into one flexible electrode to detect biomarker CD44. Their efficacy towards target of two types of probes were contrasted. Dual-channel screen-printed electrodes (SPEs) were designed innovatively. As one responsive channel, protein MIPs were synthesized through a polymerization procedure between functional monomer of alginate gel, a biocompatible antifouling chemical, and template protein CD44. Natural HA probes were immobilized to produce the other responsive channel. Such binary channels realized highly sensitive and selective target quantifying with lower limit of detections (LODs) of 1.41 × 10 -5 ng/mL for MIPs-based and 1.51 × 10 -5 ng/mL for HA-based channels, attributing to superior specificity, antifouling property and biocompatibility of MIPs and HA, satisfying stability of SPEs, high sensitivity of electrochemical techniques. The dual-responsive strategy can be extended to other batched integration of functionalized materials and active biomolecules into electrochemical and electro-catalytic biosensors towards multiple components to monitor physical signs and diagnose human diseases. © 2022, The Authors. All rights reserved.

关键词： Hyaluronic acid

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Isolation, identification, and pathogenicity of γ-hemolytic Streptococcus iniae in Selenotoca multifasciata

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Journal of the World Aquaculture Society 2025年第3期56卷

作者： Zhao, Zi-Chen Xiang, Ming-Li Zhu, Jia-Chang Wang, Yan Li, Gui-Hua Zhong, Zhi-Hong Sun, Yun Deng, Heng-Wei Guo, Wei-Liang Zhou, Yong-Can State Key Laboratory of Marine Resource Utilization in South China Sea School of Marine Biology and Fisheries Collaborative Innovation Center of Marine Science and Technology Hainan University Haikou China School of Breeding and Multiplication (Sanya Institute of Breeding and Multiplication) Hainan University Sanya China School of Life and Health Sciences Hainan University Haikou China

Streptococcus iniae is a fish pathogenic bacterium distributed worldwide. It has a wide range of hosts, strong infectivity, causes high mortality, and severely hinders the healthy development of the aquaculture industry. A fish epidemic broke out in a Selenotoca multifasciata aquaculture farm, Hainan Province, China, and resulted in numerous deaths. Sick fish showed symptoms including erratic swimming, skin darkening with generalized hemorrhages, and internal organ and brain hemorrhages. A dominant strain, SI03, isolated from the brain of a dying S. multifasciata, exhibited high virulence, and was identified as serotype I γ-hemolytic S. iniae. Subsequently, virulence gene mRNA expression, infection kinetics, as well as the histopathology in S. multifasciata infected with SI03 were analyzed. Results showed that the mRNA expression levels of scpI, simA, pdi, pgmA, and cfi genes in γ-hemolytic S. iniae SI03 were significantly higher than those in β-hemolytic S. iniae ATCC 29178. These genes are associated with adhesion, invasion, and immune evasion. While the mRNA expressions of sagA-sagI genes, which are associated with the streptolysin S, were significantly lower than those of β-hemolytic S. iniae ATCC 29178. After being challenged with SI03, the number of bacteria in all the tested fish tissues increased significantly in 24 h. The challenged fish showed symptoms similar to those of the fish from which SI03 was originally isolated. It appears that S. iniae SI03 may have developed a compensatory pathogenic mechanism for hemolysis deficiency. This mechanism enhances its adhesion, invasion, proliferation, and immune evasion abilities. The results of this research provide a reference basis for the prevention and control of S. iniae. © 2025 The Author(s). Journal of the World Aquaculture Society published by Wiley Periodicals LLC on behalf of World Aquaculture Society.

关键词： histopathology S. iniae Selenotoca multifasciata virulence genes γ-Hemolytic

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