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An octopamine-specific GRAB sensor reveals a monoamine relay circuitry that boosts aversive learning

National Science Review 2024年第05期 186-201页

作者： Mingyue Lv Ruyi Cai Renzimo Zhang Xiju Xia Xuelin Li Yipan Wang Huan Wang Jianzhi Zeng Yifei Xue Lanqun Mao Yulong Li State Key Laboratory of Membrane Biology School of Life SciencesPeking University State Key Laboratory of Brain and Cognitive Science Institute of Biophysics Chinese Academy of Sciences PKu-IDG/Mc Govern Institute for Brain Research Yuanpei College Peking University peking-tsinghua center for life sciences Academy for Advanced Interdisciplinary Studies Peking University peking university–tsinghua university–National Institute of Biological sciences joint Graduate Program Academy for Advanced Interdisciplinary Studies Peking University Institute of Molecular Physiology Shenzhen Bay Laboratory College of Chemistry Beijing Normal University Chinese Institute for Brain Research

Octopamine（OA）,analogous to norepinephrine in vertebrates,is an essential monoamine neurotransmitter in invertebrates that plays a significant role in various biological functions,including olfactory associative ***,the spatial and temporal dynamics of OA in vivo remain poorly understood due to limitations associated with the currently available methods used to detect *** overcome these limitations,we developed a genetically encoded GPCR activation-based（GRAB） OA sensor called *** sensor is highly selective for OA and exhibits a robust and rapid increase in fluorescence in response to extracellular *** GRABOA1.0,we monitored OA release in the Drosophila mushroom body（MB）,the fly's learning center,and found that OA is released in response to both odor and shock stimuli in an aversive learning *** OA release requires acetylcholine（ACh） released from Kenyon cells,signaling via nicotinic ACh ***,we discovered that OA amplifies aversive learning behavior by augmenting dopamine-mediated punishment signals via Octβ1R in dopaminergic neurons,leading to alterations in synaptic plasticity within the ***,our new GRABOA1.0sensor can be used to monitor OA release in real time under physiological conditions,providing valuable insights into the cellular and circuit mechanisms that underlie OA signaling.

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To be or not to be direct:The role of neuromedin u in neuro-eosinophil crosstalk

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Science Bulletin 2024年第2期69卷 148-150页

作者： Ruichao Liu Wenhao Shao Jun Xu Coco Chu SXMu-tsinghua Collaborative Innovation center for Frontier Medicine Taiyuan 030001China Insttute for Immunogy Department of Basic Medical SciencesSchool of Medicinesinghua UnierstyBejing 100084China tsinghua-peking center for life sciences Tsinghua UniversityBeijing 100084China Shanxi Medical university Taiyuan 030012China Department of Surgery First Hospital of Shanxi Medical UniversityShanxi Provincial Key Laboratory for Digestive Diseases and Organ TransplantationTaiyuan 030001China Beijing Key Laboratory for Immunological Research on Chronic Diseases Tsinghua UniversityBejing 100084China

With the development of new experimental techniques(e.g.,single-cell RNA sequencing(scRNA-seq),light sheet microscopy,and clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9),emerging studies have begun to uncover the interactions between the nervous system and the immune system,both in health and *** example,in mucosal tissues such as the lung and the intestine,neurotransmitters including acetylcholine[1]and adrenaline[2]can directly regulate the immune cell functions thus affect the results of allergy,asthma,and anti-pathogen host defense[3].

关键词： intestine lung asthma

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DEAD-box helicase 17(DDX17)protects cardiac function by promoting mitochondrial homeostasis in heart failure

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2774-2790页

作者： Mingjing Yan Junpeng Gao Ming Lan Que Wang Yuan Cao Yuxuan Zheng Yao Yang Wenlin Li Xiaoxue Yu Xiuqing Huang Lin Dou Bing Liu Junmeng Liu Hongqiang Cheng Kunfu Ouyang Kun Xu Shenghui Sun Jin Liu Weiqing Tang Xiyue Zhang Yong Man Liang Sun Jianping Cai Qing He Fuchou Tang Jian Li Tao Shen The Key Laboratory of Geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China peking university Fifth School of Clinical Medicine Beijing 100730China Department of Laboratory Medicine Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Biomedical Pioneering Innovation center School of Life SciencesPeking UniversityBeijing 100871China Emergency center Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Cardiology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Graduate School of peking union Medical College Beijing 100730China Department of Health Care Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China peking-tsinghua center for life sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China Department of Pathology and Pathophysiology and Department of Cardiology at Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310058China Department of Cardiovascular Surgery Peking University Shenzhen HospitalShenzhen 518036China Experimental Technology center for life sciences at Beijing Normal university Beijing 100875China

DEAD-box helicase 17(DDX17)is a typical member of the DEAD-box family with transcriptional cofactor *** DDX17 is abundantly expressed in the myocardium,its role in heart is not fully *** generated cardiomyocyte-specific Ddx17-knockout mice(Ddx17-cKO),cardiomyocyte-specific Ddx17 transgenic mice(Ddx17-Tg),and various models of cardiomyocyte injury and heart failure(HF).DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte ***-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis,leading to progressive cardiac dysfunction,maladaptive remodeling and progression to heart *** of DDX17 expression in cardiomyocytes protects cardiac function under pathological *** studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6(BCL6)and inhibit the expression of dynamin-related protein 1(DRP1).When DDX17 expression is reduced,transcriptional repression of BCL6 is attenuated,leading to increased DRP1 expression and mitochondrial fission,which in turn leads to impaired mitochondrial homeostasis and heart *** also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart *** findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

关键词： DDX17 homeostasis cardiac

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A Cullin 5-based complex serves as an essential modulator of ORF9b stability in SARS-CoV-2 replication

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3112-3129页

作者： Yuzheng Zhou Zongpeng Chen Sijie Liu Sixu Liu Yujie Liao Ashuai Du Zijun Dong Yongxing Zhang Xuan Chen Siyi Tao Xin Wu Aroona Razzaq Gang Xu De-an Tan Shanni Li Youwen Deng Jian Peng Shuyan Dai Xu Deng Xianwen Zhang Taijiao Jiang Zheng Zhang Gong Cheng Jincun Zhao Zanxian Xia Department of Cell Biology School of Life SciencesCentral South University410013 ChangshaChina Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s HospitalThe Second Affiliated HospitalSchool of MedicineSouthern University of Science and Technology518112 ShenzhenChina Department of Basic Medicine School of MedicineHunan Normal University410081 ChangshaChina Department of spine surgery The Third Xiangya HospitalCentral South University410013 ChangshaChina School of Basic Medical sciences Anhui Medical University230032 HefeiChina Hunan Key Laboratory of Neurorestoratology 921 Hospital of Joint Logistics Support Force People’s Liberation Army of China(The Second Affiliated Hospital of Hunan Normal University)410003 ChangshaHunanChina Department of Geriatric Surgery Xiangya HospitalCentral South University410008 ChangshaChina Xiangya School of Pharmaceutical sciences Central South University410013 ChangshaChina Institute of Infectious Diseases Shenzhen Bay Laboratory518132 ShenzhenChina Guangzhou Laboratory 510005 GuangzhouChina tsinghua university-peking university joint center for life sciences School of MedicineTsinghua University100084 BeijingChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical University510120 GuangzhouChina Hunan Key Laboratory of Animal Models for Human Diseases Hunan Key Laboratory of Medical Genetics&Center for Medical GeneticsSchool of Life SciencesCentral South University410008 ChangshaChina

The ORF9b protein,derived from the nucleocapsid’s open-reading frame in both SARS-CoV and SARS-CoV-2,serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune *** its significance,the precise regulatory mechanisms underlying its function remain *** the present study,we unveil that the ORF9b protein of SARS-CoV-2,including emerging mutant strains like Delta and Omicron,can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway,despite certain mutations present among these ***,our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70(TOM70)as a substrate receptor,bridging ORF9b with heat shock protein 90 alpha(HSP90α)and Cullin 5(CuL5)to form a *** this complex,CuL5 triggers the ubiquitination and degradation of ORF9b,acting as a host antiviral factor,while HSP90αfunctions to stabilize ***,treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b,leading to a pronounced inhibition of SARS-CoV-2 ***-cell sequencing data revealed an up-regulation of HSP90αin lung epithelial cells from COVID-19 patients,suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90αto evade the host *** study identifies the CuL5-TOM70-HSP90αcomplex as a critical regulator of ORF9b protein stability,shedding light on the intricate host–virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.

关键词： stability modulator offering

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Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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A Multilayered Magnetoelectric Transmitter with Suppressed Nonlinearity for Portable VLF Communication

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Research 2024年第2期2023卷 553-563页

作者： Zhaoqiang Chu Zhineng Mao Kaixin Song Shizhan Jiang Shugang Min Wei Dan Chenyuan Yu Meiyu Wu Yinghui Ren Zhichao Lu Jie Jiao Tianxiang Nan Shuxiang Dong Qingdao Innovation and Development Base Harbin Engineering UniversityQingdao 266071China College of underwater Acoustics Engineering Harbin Engineering UniversityHarbin 150001China Songshan Lake Materials Laboratory DongguanGuangdong 523808 China Shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 201800China School of Integrated Circuits and Beijing National Research center for Information Science and Technology(BNRist) Tsinghua UniversityBeijing 100084China College of Engineering Peking UniversityBeijing 100871China

Acoustically actuated magnetoelectric(ME)antenna based on the efficient oscillation of magnetic dipoles has recently been considered as a promising solution for portable very-low-frequency ***,the severe nonlinear dynamic behavior in the case of strong-field excitation results in insufficient radiation capability and poor communication performance for a conventional ME *** this work,we propose to suppress the nonlinearity of an ME antenna by neutralizing the spring-hardening effect in amorphous Metglas and the spring-softening effect in piezoelectric ceramics through an ME multilayered transmitter(ME-MLTx)*** a driving voltage of 50 V_(pp)at the resonance frequency of 21.2 kHz,a magnetic flux density as high as 108 fT at a distance of 100 m is produced from a single *** addition,ME-MLTx performs a decreased mechanical quality factor(Q_(m))less than 40.65,and,thus,a broadened bandwidth of 500 Hz is ***,a communication link transmitting binary American Standard Code for Information Interchange-coded message is built,which allows for an error-free communication with a distance of 18 m and a data rate of 300 bit/s in the presence of heavy environment *** communication distance can be further estimated over 100 m when using a femtotesla-class-inductive magnetic field *** obtained results are believed to bring ME antennas one step closer to being applicable in very-low-frequency communications.

关键词： closer nonlinearity inductive

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Single-cell omics:experimental workflow,data analyses and applications

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Science China life sciences 2024年

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biology the Institute of Biomedical Sciences and School of Life Sciences East China Normal University Beijing Institutes of life Science Chinese Academy of Sciences peking-tsinghua center for life sciences Academy for Advanced Interdisciplinary Studies Center for Quantitative Biology (CQB) Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women’s Hospital Zhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of Statistics East China Normal University Shanghai 200062 China Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji university) Ministry of Education Orthopaedic Department Tongji Hospital Bioinformatics Department School of Life Sciences and Technology Tongji University Frontier Science center for Stem Cells School of Life Sciences and Technology Tongji University Translational Medical center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East Hospital Bioinformatics Department School of Life Sciences and Technology Tongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems center for Single-cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River Delta Zhejiang University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial scRNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

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直接还是间接:神经介素u在神经-嗜酸性粒细胞交互中的作用（英文）

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Science Bulletin 2024年第2期 148-150页

作者：刘睿超邵文浩徐钧朱可可 SXMu-tsinghua Collaborative Innovation center for Frontier Medicine Institute for Immunology Department of Basic Medical Sciences School of Medicine Tsinghua University tsinghua-peking center for life sciences Tsinghua University Shanxi Medical university Department of Surgery First Hospital of Shanxi Medical University Shanxi Provincial Key Laboratory for Digestive Diseases and Organ Transplantation Beijing Key Laboratory for Immunological Research on Chronic Diseases Tsinghua University

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A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration

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Protein & Cell 2023年第5期14卷 318-336页

作者： Dawei Meng Qian Zheng Xue Zhang Xuejiao Piao Li Luo Yichang Jia tsinghua-peking joint center for life sciences Tsinghua UniversityBeijing 100084China School of life sciences Tsinghua UniversityBeijing 100084China School of Medicine Tsinghua UniversityBeijing 100084China IDG/McGovern Institute for Brain Research Tsinghua UniversityBeijing 100084China tsinghua Laboratory of Brain and Intelligence Tsinghua UniversityBeijing 100084China

Emerging evidence suggests that intron-detaining transcripts(IDTs)are a nucleus-detained and polyadenylated mRNA pool for cell to quickly and effectively respond to environmental stimuli and ***,the underlying mechanisms of detained intron(DI)splicing are still largely ***,we suggest that post-transcriptional DI splicing is paused at the Bact state,an active spliceosome but not catalytically primed,which depends on Smad Nuclear Interacting Protein 1(SNIP1)and RNPS1(a serine-rich RNA binding protein)***1 and Bact components preferentially dock at DIs and the RNPS1 docking is sufficient to trigger spliceosome *** of Snip1 attenuates neurodegeneration and globally rescues IDT accumulation caused by a previously reported mutant u2 snRNA,a basal spliceosomal ***1 conditional knockout in the cerebellum decreases DI splicing efficiency and causes ***,we suggest that SNIP1 and RNPS1 form a molecular brake to promote spliceosome pausing,and that its misregulation contributes to neurodegeneration.

关键词： SNIP1 RNPS1 spliceosome detained intron neurodegeneration

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Exploring the genetic characteristics of 93-11 and Nipponbare recombination inbred lines based on the Golden Gate SNP assay

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Science China(life sciences) 2016年第7期59卷 700-707页

作者： Renbo Yu Wei Yan Manzhong Liang Xiaojun Dai Haodong Chen Yunong Sun Xingwang Deng Xiangding Chen Hang He Liangbi Chen College of life sciences Hunan Normal University State Key Laboratory of Protein and Plant Gene Research Peking-Tsinghua Center for Life Sciences School of Advanced Agriculture Sciences and School of Life Sciences Peking University College of life sciences Capital Normal University

understanding genetic characteristics in rice populations will facilitate exploring evolutionary mechanisms and gene cloning. Numerous molecular markers have been utilized in linkage map construction and quantitative trait locus （QTL） mappings. However, segregation-distorted markers were rarely considered, which prevented understanding genetic characteristics in many populations. In this study, we designed a 384-marker GoldenGate SNP array to genotype 283 recombination inbred lines （RILs） derived from 93-11 and Nipponbare Oryza sativa crosses. using 294 markers that were highly polymorpbic between parents, a linkage map with a total genetic distance of 1,583.2 cM was constructed, including 231 segregation-distorted mark- ers. This linkage map was consistent with maps generated by other methods in previous studies. In total, 85 significant quanti- tative trait loci （QTLs） with phenotypic variation explained （PVE） values〉5% were identified. Among them, 34 QTLs were overlapped with reported genes/QTLs relevant to corresponding traits, and 17 QTLs were overlapped with reported sterili- ty-related genes/QTLs. Our study provides evidence that segregation-distorted markers can be used in linkage map construc- tion and QTL mapping. Moreover, genetic information resulting from this study will help us to understand recombination events and segregation distortion. Furthermore, this study will facilitate gene cloning and understanding mechanism of in- ter-subspecies hybrid sterility and correlations with important agronomic traits in rice.

关键词： GoldenGate SNP assay linkage map segregation-distorted markers QTLs

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