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TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis

Chinese Medical Journal 2024年第13期137卷 1592-1602页

作者： Jingyi Han Xue Zhang Menghua Cai Feng Tian Yi Xu Hui Chen Wei He Jianmin Zhang Hui Tian Department of Thoracic Surgery Qilu Hospital of Shandong UniversityJinanShandong 250012China CAMS Key Laboratory of T cell and Immunotherapy Department of ImmunologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeState Key Laboratory of Medical Molecular BiologyBeijing 100005China Changzhou Xitaihu institute for Frontier Technology of cell Therapy ChangzhouJiangsu 213000China Haihe Laboratory of cell Ecosystem Chinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

Background:Acute respiratory distress syndrome(ARDS)is a common cause of respiratory failure in many critically ill *** inflammasome activation plays an important role in the induction of acute lung injury(ALI)and ARDS,the regulatory mechanism of this process is still *** cells are stimulated by inflammation,the integrity and physiological function of mitochondria play a crucial part in ***,the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet ***,we identified the 18-kDa translocator protein(TSPO),a mitochondrial outer membrane protein,as an important mediator regulating nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome activation in macrophages during ***:TSPO gene knockout(KO)and lipopolysaccharide(LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of *** macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome *** of NLRP3 inflammasome was preformed through LPS+adenosine triphosphate(ATP)co-stimulation,followed by detection of mitochondrial membrane potential,reactive oxygen species(ROS)production,and cell death to evaluate the potential biological function of *** between two groups were performed with a two-sided unpaired ***:TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced *** deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway,promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue,including interleukin(IL)-1β,IL-18,and macrophage inflammatory protein(MIP)-*** in TSPO-KO macrophages tended to depolarize in response to cellular *** increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membr

关键词： Acute respiratory distress syndrome Acute lung injury 18-kDa translocator protein Macrophage NLRP3 inflammasome Inflammation

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Neuroinflammation revisited through the microglial lens

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Neural Regeneration Research 2025年第7期20卷 1989-1990页

作者： Renato Socodato João B.Relvas institute of Research and Innovation in Health(i3S)and institute for molecular and cell biology(IBMC) University of PortoPortoPortugal Department of Biomedicine Faculty of Medicine of the University of Porto(FMUP)PortoPortugal

Neuroimmunology is emerging as a pivotal field,shedding light on the intricate dialogues between the central nervous system(CNS)and the immune *** exploration is particularly significant in understanding microglia,the CNS’s innate immune cells,beyond the conventional conflation of“neuroinflammation”and“microglial activation.”This conflation has clouded the true complexity of these processes,potentially stalling scientific progress and the development of new *** challenge the long-standing perspectives that have oversimplified these interactions,advocating for a deeper exploration of the dynamic relationship between neuroinflammation and microglial *** dissecting specific molecular pathways,we aim to illuminate their elaborate roles in neuroinflammatory responses,especially in the context of Alzheimer’s disease(AD).Here,neuroinflammation is not merely a passive observer or a direct antagonist but a complex agent in the disease’s *** article calls for a significant paradigm shift towards an integrative,multi-omics approach to *** such a comprehensive framework is crucial for advancing our understanding of neuroinflammatory conditions and paving the way for targeted therapeutic strategies for brain diseases.

关键词： inflammation simplified activation

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Smooth muscle cell-specific genetic targeting by Myh11-driven Cre(ER) knockin mice

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Science China Life Sciences 2024年第10期67卷 2280-2282页

作者： Enci Wang Ximeng Han Haixiao Wang Kathy O.Lui Bin Zhou Lixin Wang Department of Vascular Surgery Zhongshan HospitalFudan University Department of Cardiology Shanghai Chest HospitalShanghai Jiao Tong University School of Medicine Pediatric Research institute The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Department of Chemical Pathology and Li Ka Shing institute of Health Sciences Prince of Wales HospitalThe Chinese University of Hong Kong New Cornerstone Investigator institute State Key Laboratory of Cell BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of Sciences University of Chinese Academy of Sciences Department of Vascular Surgery (Xiamen) Zhongshan hospitalFudan University

Dear editor,Site specific recombinases have been widely used for genome engineering in cardiovascular research(Fu et al., 2024;Huang et al., 2023; Xue et al., 2022). In particular, Cre is the most broadly used recombinase for cell type-specific lineage tracing and gene manipulation in mammals. For smooth muscle cell(SMC)-specific targeting, several SMC promoters including Myh11(smooth muscle myosin heavy chain), Acta2(smooth muscle a-2 actin), and SM22a(Tagln) have been used to drive Cre or CreER.

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T cell receptor signaling and cell immunotherapy

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National Science Open 2024年第4期3卷 156-171页

作者： Linsong Zhang Xinyi Xu Xiaoshan Shi Chenqi Xu Key Laboratory of Quantitative Synthetic biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China State Key Laboratory of molecular biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China

As the major sensor of adaptive immune system,T cell receptor(TCR)can recognize diverse antigens and initiate specific immune responses against invading pathogens and cancer *** the mechanisms of TCR signaling has led to the development of engineered T cell therapies,which have extensive applications in the treatment of diseases such as cancer,infection and ***,we review the current understanding of antigen-induced TCR signaling and discuss its applications in T cell therapies.

关键词： T cell receptor-CD3 complex signaling T cell therapy

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Going only half the way:cell cycle exit after the G1 restriction point

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Signal Transduction and Targeted Therapy 2024年第1期9卷 1-2页

作者： Lisa Muller Tony Gutschner Mechthild Hatzfeld Department of Pathobiochemistry Institute of Molecular MedicineMartin Luther University Halle-WittenbergCharles Tanford Protein Research CenterHalleGermany Department of RNA biology and Pathogenesis Institute of Molecular MedicineMartin Luther University Halle-WittenbergCharles Tanford Protein Research CenterHalleGermany

In a recent article published in Nature,James *** et *** that cyclin A2 levels determine whether cells will make an entrance into mitosis or whether cells will leave the cell cycle after having passed the G1/restriction(R)-point implicating that the decision is fully reversible(Fig.1).This ground-breaking study could impact future approaches for cancer treatment by targeting the mitotic clock.

关键词： point cycle

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KLF4 facilitates chromatin accessibility remodeling in porcine early embryos

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Science China(Life Sciences) 2024年第1期67卷 96-112页

作者： Wei Zhu Guowei Bu Ruifeng Hu Jixiang Zhang Lianyong Qiao Kai Zhou Tingting Wang Qiao Li Jingjing Zhang Linhui Wu Yali Xie Taotao Hu Shichun Yang Jiaqi Guan Xiaoyu Chu Juanjuan Shi Xia Zhang Falong Lu Xin Liu Yi-Liang Miao institute of Stem cell and Regenerative biology College of Animal Science and Veterinary MedicineHuazhong Agricultural UniversityWuhan 430070China Key Laboratory of Agricultural Animal Genetics Breeding and Reproduction(Huazhong Agricultural University)Ministry of EducationWuhan 430070China State Key Laboratory of molecular Developmental biology Institute of Genetics and Developmental BiologyInnovative Academy of Seed DesignChinese Academy of SciencesBeijing 100101China Frontiers Science Center for Animal Breeding and Sustainable Production Huazhong Agricultural UniversityWuhan 430070China Hubei Hongshan Laboratory Wuhan 430070China

Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early *** studies have illustrated several pioneer factors as being important for agricultural animals,but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not *** employing low-input DNase-seq(liDNase-seq),we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation *** data revealed that KLF4 played critical roles in remodeling chromatin accessibility in porcine early *** down of KLF4 led to the reduction of chromatin accessibility in early embryos,whereas KLF4 overexpression promoted the chromatin openness in porcine ***,KLF4 deficiency resulted in mitochondrial dysfunction and developmental failure of porcine *** addition,we found that overexpression of KLF4 in blastocysts promoted lipid droplet accumulation,whereas knockdown of KLF4 disrupted this *** together,our study revealed the chromatin accessibility dynamics and identified KLF4 as a key regulator in chromatin accessibility and cellular metabolism during porcine preimplantation embryo development.

关键词： porcine embryos liDNase-seq chromatin accessibility KLF4 mitochondrion lipid droplets

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Genetic insights into adaptation of alfalfa

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molecular Plant 2024年第8期17卷 1170-1171页

作者： Yafei Guo Lipeng Kang Fei Lu State Key Laboratory of Plant cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijingChina Key Laboratory of Seed Innovation Institute of Genetics and Developmental BiologyChineseAcademyof SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina CAS-JIC Centre of Excellence for Plant and Microbial Science(CEPAMS) Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijingChina

Climate change is increasingly affecting agricultural outputs,as evidenced by the changing global temperature and extreme weather events that significantly impact crop yields(Lesk et al.,2016).To address this challenge,there is a growing interest in developing crops that can endure these adverse conditions to ensure food *** examples in nature show how crops have adapted to diverse environments(Gutaker and Purugganan,2023),leaving behind a rich genomic *** genomics has started to provide insights into these adaptive processes from evolutionary and genetic perspectives(Savolainen et al.,2013;Aguirre-Liguori et al.,2021;Sang et al.,2022).Recently,Zhang et al.(Zhang et al.,2024)investigated alfalfa(Medicago sativa ***),known as the"queen of forages,"for its broad *** analyzing whole-genome sequencing data of 702 accessions from 24 Medicago species,this study enriches our understanding of how to develop crops and meet the challenges of climate change.

关键词： sativa) crops environments

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MRE11 lactylation:a linker between Warburg effect and DNA repair

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Life Metabolism 2024年第3期3卷 6-8页

作者： Pingyu Liu Hongbin Ji Fuming Li Human Phenome institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China institute of Metabolism and Integrative biology State Key Laboratory of Cell BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China University of Chinese Academy of Sciences Beijing 100049China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China School of Life Science and Technology Shanghai Tech UniversityShanghai 200120China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China

Lysine lactylation is a recently discovered post-translational modification with emerging roles in both physiology and disease.A recent study published in cell shows that lactate-induced lactylation of the homologous recombination(HR)protein meiotic recombination 11 results in HR hyperactivation and chemoresistance in cancer cells,establishing a previously unrecognized link between cellular metabolism and deoxyribonucleic acid(DNA)damage repair and providing new insights into how altered glucose metabolism can impact DNA damage response in cancer.

关键词： metabolism damage establishing

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Inbreeding and genetic load in a pair of sibling grouse species:Tetrastes sewersowi and ***

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Avian Research 2024年第2期15卷 265-270页

作者： Kai Song Tom van der Valk Bin Gao Peter Halvarsson Yun Fang Wendong Xie Siegfried Klaus Zhiming Han Yue-Hua Sun Jacob Hoglund Key Laboratory of Animal Ecology and Conservation biology Institute of ZoologyChinese Academy of SciencesBeijing100101China Animal Ecology Department of Ecology and GeneticsUppsala UniversityNorbyvagen 18DUppsala75236Sweden Department of cell and molecular biology Uppsala75273Sweden Unit of Parasitology Department of Biomedicine and Veterinary Public HealthSwedish University of Agricultural SciencesPO Box 7036Uppsala75007Sweden Lindenhohe 5 JenaD-07749Germany The State Key Laboratory of Reproductive biology Institute of ZoologyChinese Academy of SciencesBeijing100101China

Genetic load and inbreeding are recognized as important factors to be considered in conservation *** levels of both can increase the risk of population extinction by negatively impacting fitness-related characters in many species of plants and animals,including humans(inbreeding depression).Genomic tech-niques are increasingly used in measuring and understanding genetic load and inbreeding and their importance in evolution and *** used whole genome resequencing data from two sibling grouse species in subarctic Eurasia to quantify *** found a large range of inbreeding measured as FROH(fraction of runs of homozygosity)in individuals from different populations of Chinese Grouse(Tetrastes sewerzowi)and Hazel Grouse(***).FROH estimated from genome-wide runs of homozygosity(ROH)ranged from 0.02 to 0.24 among Chinese Grouse populations and from 0.01 to 0.44 in Hazel *** from a population of Chinese Grouse residing in the Qilian mountains and from the European populations of Hazel Grouse(including samples from Sweden,Germany and Northeast Poland)were the most inbred(FROH ranged from 0.10 to 0.23 and 0.11 to 0.44,respectively).These levels are comparable to other highly inbred populations of *** Grouse from northern China and Chinese Grouse residing in the Qinghai-Tibetan Plateau showed relatively lower inbreeding *** of the ratio between deleterious missense mutations and synonymous mutations revealed higher levels in Chinese Grouse as compared to Hazel *** results are possibly explained by higher fixation rates,mutational melt down,in the range-restricted Chinese Grouse compared to the wide-ranging Hazel ***,when we compared the relatively more severe class of loss-of-function muta-tions,Hazel Grouse had slightly higher levels than Chinese Grouse,a result which may indicate that purifying selection(purging)has been more efficient in Chinese Grouse on this class of mutations.

关键词： Genetic load Inbreeding Purifying selection Qinghai-Tibetan Plateau ROH Tetrastes

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Aagab is required for zebrafish larval development by regulating neural activity

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Journal of Genetics and Genomics 2024年第6期51卷 630-641页

作者： Shihui Ding Tursunjan Aziz Anming Meng Shunji Jia State Key Laboratory of Membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Guangzhou Laboratory GuangzhouGuangdong 510320China State Key Laboratory of molecular Developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Clathrin-mediated endocytosis has been implicated in various physiological processes,including nutrient uptake,signal transduction,synaptic vesicle recycling,maintenance of cell polarity,and antigen *** prior knowledge of its importance as a key regulator in promoting clathrin-mediated endocytosis,the physiological function of α-and γ-adaptin binding protein(aagab)remains *** this study,we investigate the biological function of aagab during zebrafish *** establish a loss-of-function mutant of aagab in zebrafish,revealing impaired swimming and early larval *** the high expression level of aagab in the brain,we probe into its physiological role in the nervous *** mutants display subdued calcium responses and local field potential in the optic tectal neurons,aligning with reduced neurotransmitter release(e.g.,norepinephrine)in the tectal neuropil of aagab *** aagab mRNA or nervous stimulant treatment in mutants restores neurotransmitter release,calcium responses,swimming ability,and ***,our observations show delayed release of FM 1-43 in AAGAB knockdown differentiated neuroblastoma cells,pointing towards a probable link to defective clathrin-mediated synaptic vesicle *** conclusion,our study underscores the significance of Aagab in neurobiology and suggests its potential impacts on neurological disorders.

关键词： Aagab Endocytosis Neural activity Synaptic transmitter release Zebrafish

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