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HTR2A agonists play a therapeutic role by restricting ILC2 activation in papain-induced lung inflammation

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Cellular & Molecular Immunology 2023年第4期20卷 404-418页

作者： Zhishuo Wang Chenghua Yan Qizhen Du Yuying Huang Xuezhen li Dan Zeng Ruizhi Mao Rama Krishna Gurram Shipeng Cheng Wangpeng Gu lin Zhu Weiguo Fan liyan Ma Zhiyang ling Ju Qiu dangsheng li Enmei liu Yaguang Zhang Yiru Fang Jinfang Zhu Bing Sun state Key Laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of Sciences320 Yueyang RoadShanghai 200031China College of life Sciences Jiangxi University of Chinese MedicineNanchang 330004China Department of Respiratory Medicine Children's Hospital of Chongqing Medical University National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqingChina Department of Allergy Chongqing General HospitalChongqingChina Clinical Research Center and Division of Mood Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Laboratory of Immune System Biology National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMD 20892USA CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China Shanghai Key Laboratory of Psychotic Disorders Shanghai 201108China.

Group 2 innate lymphoid cells(ILC2s)are a category of heterogeneous cells that produce the cytokines IL-5 and IL-13,which mediate the type 2 immune response.However,specific drug targets on lung ILC2s have rarely been reported.Previous studies have shown that type 2 cytokines,such as IL-5 and IL-13,are related to depression.Here,we demonstrated the negative correlation between the depression-associated monoamine neurotransmitter serotonin and secretion of the cytokines IL-5 and IL-13 by ILC2s in individuals with depression.Interestingly,serotonin ameliorates papain-induced lung inflammation by suppressing ILC2 activation.Our data showed that the serotonin receptor HTR2A was highly expressed on ILC2s from mouse lungs and human PBMCs.Furthermore,an HTR2A selective agonist(DOI)impaired ILC2 activation and alleviated the type 2 immune response in vivo and in vitro.Mice with ILC2-specific depletion of HTR2A(Il5^(cre/+)·Htr2a^(flox/flox)mice)abolished the DOI-mediated inhibition of ILC2s in a papain-induced mouse model of inflammation.In conclusion,serotonin and DOI could restrict the type 2 lung immune response,indicating a potential treatment strategy for type 2 lung inflammation by targeting HTR2A on ST2+ILC2s.

关键词： Serotonin(5-HT) HTR2A DOl Group 2 innate lymphoid cell Type 2 lung inflammation

The PIWI-specific insertion module helps load longer piRNAs for translational activation essential for male fertility

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Science China(life Sciences) 2023年第7期66卷 1459-1481页

作者： Xin Wang Di-Hang lin Yue Yan An-Hui Wang Jiaoyang liao Qian Meng Wen-Qing Yang Heng Zuo Min-Min Hua Fengjuan Zhang Hongwen Zhu Hu Zhou Tian-Yu Huang Rui He Guangyong li Yue-Qiu Tan Hui-Juan Shi Lan-Tao Gou dangsheng li ligang Wu Yonggang Zheng Xiang-Dong Fu Jinsong li Rujuan liu Guo-Hui li Mo-Fang liu Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou310024China State Key Laboratory of Molecular Biology State Key Laboratory of Cell BiologyShanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai200031China Laboratory of Molecular Modeling and Design State Key Laboratory of Molecular Reaction DynamicsDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023China Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China School of life Science and Technology ShanghaiTech UniversityShanghai201210China NHC Key Lab of Reproduction Regulation(Shanghai Institute for Biomedical and Pharmaceutical Technologies) Fudan UniversityShanghai200032China Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan750004China Department of Urology General Hospital of Ningxia Medical UniversityNingxia Medical UniversityYinchuan750004China Institute of Reproductive and Stem Cell Engineering College of Basic of MedicineCentral South UniversityChangsha410000China Department of Physiology Howard Hughes Medical InstituteUniversity of Texas Southwestern Medical CenterDallasTX75390USA Westlake Laboratory of life Sciences and Biomedicine School of Life SciencesWestlake UniversityHangzhou310024China

PIWI-clade proteins harness pi RNAs of 24–33 nt in length.Of great puzzles are how PIWI-clade proteins incorporate pi RNAs of different sizes and whether the size matters to PIWI/pi RNA function.Here we report that a PIWI-Ins module unique in PIWIclade proteins helps define the length of pi RNAs.Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter pi RNAs and causes spermiogenic failure in mice,demonstrating the functional importance of this regulatory module.Mechanistically,we show that longer pi RNAs provide additional complementarity to target m RNAs,thereby enhancing the assembly of the MIWI/e IF3f/Hu R super-complex for translational activation.Importantly,we identify a c.1108C>T(p.R370W)mutation of HIWI(human PIWIL1)in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer pi RNAs.These findings reveal a critical role of PIWI-Ins-ensured longer pi RNAs in fine-tuning MIWI/pi RNA targeting capacity,proven essential for spermatid development and male fertility.

关键词： PIWI piRNAs PIWI-Ins translational activation spermatid development male fertility

JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone formation in mice

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分子细胞生物学报:英文版 2015年第1期7卷 23-34页

作者： Feng Zhang Longyong Xu Longxia Xu Qing Xu dangsheng li Yingzi Yang Gerard Karsenty Charlie Degui Chen State Key Laboratory of Molecular Biology Shanghai Key Laboratory of Molecular AndrologyInstitute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Department of Pathology State Key Laboratory of Cancer BiologyXijing HospitalFourth Military Medical UniversityShaanxi 710032China Shanghai Information Center for life Sciences Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China National Human Genome Research Institute National Institutes of HealthBethesdaMD 20892USA Department of Genetics and Development College of Physicians and SurgeonsColumbia UniversityNew YorkNY 10032USA

JMJD3(KDM6B)is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression.However,the function of JMJD3 in vivo is not well understood.Here we show that JMJD3 is highly expressed in cells of the chondrocyte lineage,especially in prehypertrophic and hypertrophic chondrocytes,during endochondral ossification.Homozygous deletion of Jmjd3 results in severely decreased proliferation and delayed hypertrophy of chondrocytes,and thereby marked retardation of endochondral ossification in mice.Genetically,JMJD3 associates with RUNX2 to promote proliferation and hypertrophy of chondrocytes.Biochemically,JMJD3 associates with and enhances RUNX2 activity by derepression of Runx2 and Ihh transcription throughits H3K27me3 demethylase activity.These results demonstrate that JMJD3 is a key epigenetic regulator in the process of cartilage maturation during endochondral bone formation.

关键词： JMJD3 RUNX2 chondrocyte endochondral bone formation

Endothelial progenitor cells in debate

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Cell Research 2006年第6期16卷 9-9页

作者： dangsheng li

Adult stem/progenitor cells play important roles in tissue homeostasis and have important implications for regenerativemedicine.It was once thought that formation of new blood vessels in adult only occurs through angiogenesis,a processwhereby new vessels are formed from existing mature endothelial cells;while vasculogenesis,where new vessels arederived from differentiation of endothelial progenitor cells(EPCs),was thought to occur exclusively in embryos.Thediscovery of adult EPCs a few years ago has changed this old paradigm;and subsequent studies showed that EPCs maybe a promising tool for the treatment of vascular disorders.However,there have been conflicting reports on subtypes,surface markers,and functions of EPCs;and thus the exact origin and identity of EPCs remain to be defined.A commonapproach to obtain EPCs is to isolate and culture mononuclear cells from peripheral blood and to select adherent cells for

关键词： EPCs Endothelial progenitor cells in debate

The 2009 pandemic A/Wenshan/01/2009 H1N1 induces apoptotic cell death in human airway epithelial cells

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分子细胞生物学报:英文版 2011年第4期3卷 221-229页

作者： Ning Yang Xiaoxu Hong Penghui Yang Xiangwu Ju Yuguo Wang Jun Tang Chenggang li Quanshui Fan Fuqiang Zhang Zhongwei Chen li Xing Zhongpeng Zhao Xiao Gao Guoyang liao Qihan li Xiliang Wang dangsheng li Chengyu Jiang State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesPeking Union Medical CollegeTsinghua UniversityChinese Academy of Medical SciencesBeijing 100005China Department of Viral Immunology Institute of Medical BiologyChinese Academy of Medicine SciencePeking Union Medical CollegeKunming 650118China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Centre for Disease Prevention and Control Cheng Du Military RegionKunming 650032China Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200031China

In 2009,a novel swine-origin H1N1 influenza virus emerged in Mexico and quickly spread to other countries,including China.This 2009 pandemic H1N1 can cause human respiratory disease,but its pathogenesis remains poorly understood.Here,we studied the infection and pathogenesis of a new 2009 pandemic strain,A/Wenshan/01/2009 H1N1,in China in human airway epithelial cell lines compared with contemporary seasonal H1N1 influenza virus.Our results showed that viral infection by the A/Wenshan H1N1 induced significant apoptotic cell death in both the human nasopharyngeal carcinoma cell line CNE-2Z and the human lung adenocarcinoma cell line A549.The A/Wenshan H1N1 virus enters both of these cell types more efficiently than the seasonal influenza virus.Viral entry in both cell lines was shown to be mediated by clathrin-and dynamin-dependent endocytosis.Therefore,we discovered that the 2009 pandemic H1N1 strain,A/Wenshan/01/2009,can induce apoptotic cell death in epithelial cells of the human respiratory tract,suggesting a molecular pathogenesis for the 2009 pandemic H1N1.

关键词： apoptosis respiratory S-OIV H1N1 influenza virus

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压裂双弯头液固两相流冲蚀影响数值分析

润滑与密封 2024年第1期49卷 9-14页

作者：代四维樊建春张党生杨思齐李杰中国石油大学(北京)安全与海洋工程学院北京102249 中国石油大学(北京)应急管理部油气生产安全与应急技术重点实验室北京102249 中国石油集团渤海钻探工程有限公司井下作业分公司河北沧州062552 中国石油集团工程材料研究院石油管材及装备材料服役行为与结构安全国家重点实验室陕西西安710077

在水力压裂过程中,地面高压管汇受管内携砂压裂液的复杂流动影响,长期承受着严峻的冲蚀破坏。在各类高压管汇构件中,弯管的冲蚀损伤最为严重。为改善压裂双弯头冲蚀磨损状况,采用DPM模型、RNG k-ε湍流模型,综合分析了斯托克斯数(St)、... 详细信息

在水力压裂过程中,地面高压管汇受管内携砂压裂液的复杂流动影响,长期承受着严峻的冲蚀破坏。在各类高压管汇构件中,弯管的冲蚀损伤最为严重。为改善压裂双弯头冲蚀磨损状况,采用DPM模型、RNG k-ε湍流模型,综合分析了斯托克斯数(St)、重力方向、粒径及流速对串联双弯头冲蚀磨损的影响。结果表明:冲蚀磨损区域主要由St和重力方向共同决定;St1时呈指数增长;St相同时,速度对冲蚀磨损程度的影响远比颗粒尺寸强烈;向下流重力方向下,损伤区域随St增加完全转移至第二弯头的临界粒径显著小于向上流临界粒径;重力方向对同向冲击颗粒的冲蚀损伤虽有增强效应,其对冲蚀磨损程度影响远不及颗粒尺寸因素作用大。

关键词：高压管汇双弯头液固两相流冲蚀磨损斯托克斯数

辅调节因子NRIF3受体特异性之机理的研究

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武汉大学学报（医学版） 2005年第2期26卷 194-198页

作者：王芳黄汉涛 dangsheng li Herbert H.Samules 武汉大学人民医院内分泌科武汉430060 湖北省宜昌市夷陵医院内一科宜昌443100 Dept.of Medicine New York Universty Medical CenterNewYorkUSA

目的:研究新发现的核激素受体辅调节因子(coregulator) NRIF3 的受体特异性的分子机理。方法:酵母双杂合体转化分析,选择典型菌株作β 半乳糖苷酶定量分析。结果:我们的结果提示一个双区结合模型,即单个NRIF3分子同时利用C端的LXXIL(受... 详细信息

目的:研究新发现的核激素受体辅调节因子(coregulator) NRIF3 的受体特异性的分子机理。方法:酵母双杂合体转化分析,选择典型菌株作β 半乳糖苷酶定量分析。结果:我们的结果提示一个双区结合模型,即单个NRIF3分子同时利用C端的LXXIL(受体结合功能区,即 RID1)和 N端的 LXXLL(RID2)与 TR或 RXR作用,RID1和RID2之间的距离对受体和NRIF3相互作用的亲和力有重要影响。结论:辅调节因子 NRIF3 受体特异性与其结构有关。

关键词：辅调节因子受体特异性分子机理

Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells

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Cell Research 2007年第7期17卷 627-637页

作者： Qi Cao1,2 li Wang1,2 Fang Du1,2 Huiming Sheng1,2 Yan Zhang1,2 Juanjuan Wu1,2 Baihua Shen1,2 Tianwei Shen1,2 Jingwu Zhang1,2 dangsheng li Ningli li1,21 Department of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China2 Shanghai Institute of Immunology, 280 South Chongqing Road, Shanghai 200025, China3 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China Department of Immunology Shanghai Jiao Tong University School of Medicine Shanghai China Shanghai Institute of Immunology Shanghai China Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumorimmunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previouslyreported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity andupregulated Th1 responses in vivo. However, the underlying molecular mechanisms are not well understood. Here weshow that Treg function was significantly downregulated in mice that received immunization of attenuated activatedautologous T cells. We found that Foxp3 expression decreased in CD4+CD25+ T cells from the immunized mice.Moreover, CD4+CD25+Foxp3+ Treg obtained from immunized mice exhibited diminished immunosuppression abilitycompared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high levelof anti-CD25 antibody (about 30ng/ml, plikely contributes to enhanced Thl response in immunized mice and is at least part of themechanism underlying the boosted anti-tumor immunity.

关键词： immunization with activated autologous T cells CD4+CD25+Foxp3+Treg anti-CD25 antibody serum adoptive transfer

Surface texturing for adaptive Ag/MoS_2 solid lubricant plating

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Rare Metals 2012年第6期31卷 560-565页

作者： Huang Zhongjia liu Minglang Xiong dangsheng li Jianliang Anhui Polytech Univ Anhui Key Lab High Performance Nonferrous Met Mat Wuhu 241000 Peoples R China Nanjing Univ Sci & Technol Dept Mat Sci & Engn Nanjing 210094 Jiangsu Peoples R China

The objective of this research is to prepare specially designed surface texture on hard steel surface by electrochemical micromachining (EM) and to incorporate electroless plated Ag/MoS2 solid lubricant coating into the dimples of EM textured steel surface to effectively reduce friction and wear of steel-steel contacts. The friction and wear behavior of the Ag/MoS2 solid lubricant coating on EM textured steel surface was evaluated in relation to the size and spacing of the dimples thereon. The microstructure of as-plated Ag/MoS2 solid lubricant coating and the morphology and elemental composition of the worn coating surface and counterface steel surface were analyzed by means of optical microscopy, scanning electron microscopy, and energy dispersive spectrometry. It is found that electroless plated Ag/MoS2 coating is able to greatly reduce the friction and wear of the EM textured steel disc coupled with GCr15 steel ring, mainly because of the formation of solid self-lubricating layer on the EM textured steel surface and of transferred lubricating film on counterface steel surface. The diameter and spacing of the dimples are suggested as 500 μm for acquiring the best wear resistance of the hard steel discs after electrochemical micromachining treatment and electroless plating of Ag/MoS2 solid lubricating coating.

关键词： hard steel electrochemical micromachining surface texturing electroless plating Ag/MoS2 lubricating coating behavior friction and wear