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Virologica Sinica 2024年第2期39卷 301-308页

作者： Qiu-Yan Zhang Jia-Qi Li Qi Li Yang Zhang Zhe-Rui Zhang Xiao-Dan Li Hong-Qing Zhang Cheng-Lin Deng Feng-Xia Yang Yi Xu Bo Zhang The Joint Center of translational Precision medicine Department of Infections and DiseasesGuangzhou Institute of PediatricsGuangzhou Women and Children's Medical CenterGuangzhou510623China Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Science and Technology of China Department of Life Sciences and MedicineHefei230026China Hunan Normal University School of MedicineChangsha410081China

Hand,foot,and mouth disease(HFMD)is a common pediatric illness mainly caused by enteroviruses,which are important human ***,there are no available antiviral agents for the therapy of enterovirus *** this study,an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was *** this screening system,we screened a drug library containing 1042 natural compounds to identify potential EV-A71 ***(FAN),a bis-benzylisoquinoline alkaloid,exhibits potential inhibitory effects against various enteroviruses that cause HFMD,such as EV-A71,CV-A10,CV-B3 and *** investigations revealed that FAN targets the early stage of the enterovirus life *** the selection of FAN-resistant EV-A71 viruses,we demonstrated that the VP1 protein could be a potential target of FAN,as two mutations in VP1(E145G and V258I)resulted in viral resistance to *** research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

关键词： Hand,foot,and mouth disease(HFMD) Enterovirus EV-A71 High-content screening Fangchinoline(FAN)

Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

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Food Science and Human Wellness 2024年第4期13卷 2289-2309页

作者： Jie Zhang Shuang Yang Baocai Xu Zihui Qin Xinyi Guo Ben Wei Qinghua Wu Kamil Kuca Tushuai Li Wenda Wu School of Biology and Food Engineering Changshu Institute of TechnologySuzhou 215500China Center for Clinical Mass Spectrometry School of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary MedicineNanjing Agricultural UniversityNanjing 210095China Department of Chemistry Faculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic College of Life Science Yangtze UniversityJingzhou 434025China Wuxi Medical College Jiangnan UniversityWuxi 214122China Wuxi translational medicine Research Center and Jiangsu translational medicine Research Institute Wuxi Branch Wuxi 214013China

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to *** podocytes are terminally differentiated epithelial ***_(1)induces podocyte inflammation,proteinuria and renal *** the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse *** of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte *** also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway *** of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney *** findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte *** study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

关键词： Aflatoxin B_(1) Podocyte inflammation miRNA-9 Chemokine(C-X-C motif)receptor 4 RelA ubiquitin-dependent degradation

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity

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Signal Transduction and Targeted Therapy 2024年第1期9卷 259-270页

作者： Yan Sun Xiu-Na Yang Shuang-Shuang Yang Yi-Zhu Lyu Bing Zhang Kai-Wen Liu Na Li Jia-Chen Cui Guang-Xiang Huang Cheng-Lin Liu Jie Xu Jian-Qing Mi Zhu Chen Xiao-Hu Fan Sai-Juan Chen Shuo Chen Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Hematology Second Hospital of Dalian Medical UniversityDalian 116023China national Facility for Protein Science Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Legend Biotech China Nanjing 211112China Shanghai Immune Therapy Institute Shanghai Cancer InstituteState Key Laboratory of Oncogenes and Related GenesRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Wondercel Biotechnology Shenzhen 518052China

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular ***,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based *** co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple *** we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated *** analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in ***-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived *** results provide a framework for contemplating the AIM approach in designing next-generation CARs.

关键词： cytotoxicity Antigen elevated

Celastrol regulates the oligomeric state and chaperone activity of αB-crystallin linked with protein homeostasis in the lens

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Fundamental Research 2024年第2期4卷 394-400页

作者： Huaxia Wang Qing Tian Ying Zhang Yibo Xi Lidan Hu Ke Yao Jingyuan Li Xiangjun Chen Eye Center of the Second Affiliated Hospital Zhejiang University School of Medicine88 Jiefang RoadHangzhou 310009China Institute of translational medicine Zhejiang University School of Medicine268 Kaixuan RoadHangzhou 310020China. State Key Laboratory of Membrane Biology School of Life SciencesTsinghua UniversityBeijing 100084China The Children’s Hospital Zhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Zhejiang Province Key Laboratory of Quantum Technology and Device Department of PhysicsZhejiang UniversityZheda Road 38Hangzhou 310027China

Protein misfolding and aggregation are crucial pathogenic factors for cataracts,which are the leading cause of visual impairment worldwide.α-crystallin,as a small molecular chaperone,is involved in preventing protein misfolding and maintaining lens *** chaperone activity of α-crystallin depends on its oligomeric *** previous work identified a natural compound,celastrol,which could regulate the oligomeric state of α*** this work,based on the UNcle and SEC analysis,we found that celastrol induced𝛼αB-crystallin to form large *** oligomer formation enhanced the chaperone activity of αB-crystallin and prevented aggregation of the cataract-causing mutant α*** interactions between𝛼αB-crystallin and celastrol were detected by the FRET(Fluorescence Resonance Energy Transfer)technique,and verified by molecular *** least 9 binding patterns were recognized,and some binding sites covered the groove structure of α***,αB-R120G,a cataract-causing mutation located at the groove structure,and celastrol can decrease the aggregates of α***,our results suggested celastrol not only promoted the formation of large αB-crystallin oligomers,which enhanced its chaperone activity,but also bound to the groove structure of its α-crystallin domain to maintain its structural *** might serve as a chemical and pharmacological chaperone for cataract treatment.

关键词： αB-crystallin Celastrol Interactions Oligomeric state Chaperone activity Structural stability

Isolation and microbial transformation of tea sapogenin from seed pomace of Camellia oleifera with anti-inflammatory effects

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Chinese Journal of Natural medicines 2024年第3期22卷 280-288页

作者： SHEN Pingping JIANG Xuewa ZHANG Jingling WANG Jiayi Raj Richa LI Guolong GE Haixia WANG Weiwei YU Boyang ZHANG Jian State Key Laboratory of Natural medicines China Pharmaceutical UniversityNanjing 210009China Co-construction Collaborative Innovation Center for Chinese medicine Resources Industrialization by Shaanxi&Education Ministry Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation ResearchShaanxi University of Chinese MedicineXianyang 712046China School of Life Sciences Huzhou UniversityHuzhou 313000China Nanjing Hospital of Chinese medicine Affiliated to Nanjing University of Chinese medicine Nanjing 210046China Jiangsu Key Laboratory of TCM Evaluation and translational Research China Pharmaceutical UniversityNanjing 211198China

In the current study,tea saponin,identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel.,was meticulously extracted and hydrolyzed to yield five known sapogenins:16-O-tiglogycamelliagnin B(a),camelliagnin A(b),16-O-angeloybarringtogenol C(c),theasapogenol E(d),theasapogenol F(e).Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites(a1−a6).The anti-inflammatory potential of these compounds was assessed using pathogenassociated molecular patterns(PAMPs)and damage-associated molecular patterns molecules(DAMPs)-mediated cellular inflammation ***,compounds b and a2 demonstrated significant inhibitory effects on both lipopolysaccharide(LPS)and high-mobility group box 1(HMGB1)-induced inflammation,surpassing the efficacy of the standard anti-inflammatory agent,***,compounds d,a3,and a6 selectivity targeted endogenous HMGB1-induced inflammation,showcasing a pronounced *** results underscore the therapeutic promise of *** seed pomace-derived compounds as potent agents for the management of inflammatory diseases triggered by infections and tissue damage.

关键词： Camellia oleifera Seed pomace Tea sapogenin Microbial transformation Damage-associated molecular patterns and Pathogen-associated molecular patterns Anti-inflammatory activity

Broadening environmental research in the era of accurate protein structure determination and predictions

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Frontiers of Environmental Science & Engineering 2024年第7期18卷 169-178页

作者： Mingda Zhou Tong Wang Ke Xu Han Wang Zibin Li Wei-xian Zhang Yayi Wang State Key Laboratory of Pollution Control and Resources Reuse Shanghai Institute of Pollution Control and Ecological SecurityCollege of Environmental Science and EngineeringTongji UniversityShanghai 200092China translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People's HospitalSchool of MedicineTongji UniversityShanghai 200434China

The deep-learning protein structure prediction method AlphaFold2 has garnered enormous attention beyond the realm of structural biology,for its groundbreaking contribution to solving the"protein foiding problem"In this perspective,we explore the connection between protein structure studies and environmental research,delving into the potential for addressing specific environmental *** are promising for environmental applications because of the functional diversity endowed by their structural ***,structural studies on proteins with environmental significance remain ***,we present the opportunity to study proteins by advancing experimental determination and deep-learning prediction ***,the latest progress in environmental research via cryogenic electron microscopy is *** allows us to determine the structure of protein complexes in their native state within cells at molecular resolution,revealing environmentally-associated structural *** the remarkable advancements in computational power and experimental resolution,the study of protein structure and dynamics has reached unprecedented depth and *** advancements will undoubtedly accelerate the establishment of comprehensive environmental protein structural and functional *** opportunities for protein engineering exist to enable innovative solutions for environmental applications,such as the degradation of persistent contaminants,and the recovery of valuable metals as well as rare earth elements.

关键词： Environmental proteins Protein structure Cryogenic electron microscopy Protein structure prediction Protein engineering Artificial Intelligence

Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis

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Bone Research 2024年第1期12卷 215-226页

作者： Yuhang Liu Ruihan Hao Jia Lv Jie Yuan Xuelei Wang Churong Xu Ding Ma Zhouyi Duan Bingjun Zhang Liming Dai Yiyun Cheng Wei Lu Xiaoling Zhang Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine(SJTUSM)Shanghai 200092China national Facility for translational medicine Shanghai 200240China Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai 200241China Department of Orthopaedic Surgery The Second Hospital of Shanxi Medical UniversityTaiyuan 030001China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China School of medicine Shanghai UniversityShanghai 200444China

Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat *** attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in *** this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice *** address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in ***,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived ***,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 *** knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient *** by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine ***,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

关键词： osteoarthritis metabolism inhibited

ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3027-3048页

作者： Mengdie Dong Yunjia Zhang Minghong Chen Yongkang Tan Jiao Min Xian He Fuhao Liu Jiaming Gu Hong Jiang Longbin Zheng Jiajing Chen Quanwen Yin Xuesong Li Xiang Chen Yongfeng Shao Yong Ji Hongshan Chen Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical Universityand Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNational Vaccine Innovation PlatformNanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Clinical medicine Nanjing Medical University TIANYUAN Honors SchoolNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineState Key Laboratory of Reproductive MedicineSchool of Pharmacythe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversityNanjing 211166China national Key Laboratory of Frigid Zone Cardiovascular Diseases(NKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China)College of PharmacyKey Laboratory of Cardiovascular Medicine Research and Key Laboratory of Myocardial IschemiaChinese Ministry of EducationNHC Key Laboratory of Cell Transplantationthe Central Laboratory of the First Affiliated HospitalHarbin Medical UniversityHarbin 150081China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Endothelial-to-mesenchymal transition(EndMT)is a key driver of *** glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate *** lactylation,mediated by lactate,can regulate gene expression and participate in disease ***,whether histone lactylation is involved in atherosclerosis remains ***,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’***,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting *** found that deletion of ASF1A inhibited EndMT and improved endothelial *** analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis *** of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced *** study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.

关键词： Histone lactylation Atherosclerosis Endothelial-tomesenchymal transition ASF1A SNAI1 Endothelial dysfunction Lactate Epigenetic

Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

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Engineering 2024年第5期36卷 178-192页

作者： Ruogu Qi Shanshan Wang Jiayi Yu Tianming Lu Zhiqiang Bi Weibo Liu Yuanyuan Guo Yong Bian Jianliang Shen Xuesong Zhang Wenhao Hu School of medicine Nanjing University of Chinese MedicineNanjing 210023China Laboratory Animal Center Nanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Carcinogenesis and translational Research Ministry of Education/BeijingDepartment of Radiation OncologyBeijing Cancer HospitalBeijing 100142China Department of Orthopedics The Fourth Medical CenterThe Chinese People’s Liberation Army General HospitalBeijing 100853China State Key Laboratory of Ophthalmology Optometry and Vision ScienceSchool of Biomedical EngineeringWenzhou Medical UniversityWenzhou 325027China

Multiple myeloma(MM)is the second most prevalent hematological *** MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic *** study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@*** results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in ***,this material demonstrated a capability for drug release triggered by low pH ***,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM ***,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic ***,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

关键词： Multiple myeloma Bortezomib Drug delivery Dual targeting Controlled release

Real-World Treatment Adherence to Smoking Cessation Medications and Association with Treatment Outcome—27 centers,China,2017–2022

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China CDC weekly 2024年第22期6卷 522-529,I0001-I0003页

作者： Anqi Cheng Zhao Liu Xinmei Zhou Zheng Su Dan Xiao Chen Wang the China national Tobacco Cessation Cohort Study(CNTCCS)Study Group Department of Tobacco Control and Prevention of Respiratory Disease Center of Respiratory MedicineChina-Japan Friendship Hospital/WHO Collaborating Center for Tobacco Cessation and Respiratory Diseases Prevention/National Center for Respiratory Medicine/National Clinical Research Center for Respiratory Diseases/Institute of Respiratory MedicineChinese Academy of Medical SciencesBeijingChina Department of Pulmonary and Critical Care medicine Center of Respiratory MedicineChina-Japan Friendship Hospital/WHO Collaborating Center for Tobacco Cessation and Respiratory Diseases Prevention/China National Center for Respiratory Medicine/China National Clinical Research Center for Respiratory DiseasesBeijingChina Chinese Academy of Medical Sciences and Peking Union Medical College BeijingChina 不详

What is already known about this topic?Medication non-adherence significantly impedes smoking cessation *** effective smoking cessation medications are accessible in China,realworld adherence and its correlation with treatment outcomes remain largely *** is added by this report?From December 2017 to January 2022,1,120 participants were recruited from 27 centers in all seven geographical regions of *** revealed that only 38.2%of smokers adhered to the prescribed 12-week smoking cessation treatment and those with a higher education level were more likely to be *** addition,smokers with good adherence were more likely to successfully quit *** are the implications for public health practice?The data obtained could enhance our understanding of smoking cessation practices in *** adherence is a crucial strategy to enhance the effectiveness of smoking cessation treatments and management provided to smokers.

关键词： China. smoke likely