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Mpox(formerly monkeypox):pathogenesis,prevention,and treatment

Signal Transduction and Targeted Therapy 2024年第1期9卷 234-248页

作者： Junjie Lu Hui Xing Chunhua Wang Mengjun Tang Changcheng Wu Fan Ye Lijuan Yin Yang Yang Wenjie Tan Liang Shen Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and ScienceHubei ProvinceXiangyang 441021China nhc key laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China College of biotechnology Tianjin University of Science&TechnologyTianjin 300457China Shenzhen key laboratory of Pathogen and Immunity National Clinical Research Center for infectious diseaseState Key Discipline of Infectious DiseaseShenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China

In 2022,a global outbreak of Mpox(formerly monkeypox)occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions.The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus.Consequently,nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination.Nevertheless,the available therapeutic options for Mpox virus infection remain limited.So far,only a few numbers of antiviral compounds have been approved by regulatory authorities.Given the high mutability of the Mpox virus,certain mutant strains have shown resistance to existing pharmaceutical interventions.This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism.Currently,there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox.To address this issue,we conducted a review covering the physiological and pathological processes of Mpox infection,summarizing the latest progress of anti-Mpox drugs.Our analysis encompasses approved drugs currently employed in clinical settings,as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox.Furthermore,we have gained valuable insights from the process of Mpox drug development,including strategies for repurposing drugs,the discovery of drug targets driven by artificial intelligence,and preclinical drug development.The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.

关键词： prevention treatment intensified

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Infection with SARS-CoV-2 can cause pancreatic impairment

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin nhc key laboratory of Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing key laboratory of Cardiometabolic Molecular Medicine Peking UniversityBeijing 100871China State key laboratory of Biomembrane and Membrane biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of Engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China International Co-operation laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China National laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping National laboratory(CPNL) Beijing 102206China State key laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes.Herein,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients.Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans.Minor and limited phenotypic and histopathological changes were observed in adult models.Systemic proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio levels.Furthermore,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic dysfunction.In contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

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Gut liver brain axis in diseases:the implications for therapeutic interventions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 79-104页

作者： Mengyao Yan Shuli Man Benyue Sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao State key laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&Technology300457 TianjinChina National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Tianjin key laboratory for Modern Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin Road300072 TianjinChina

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous systems.In the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment strategies.In this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain axis.Some therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain axis.Besides,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)analogs.Targeting gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related therapies.Targeting liver-brain axis contains epigenetic regulation and Aβmetabolism-related therapies.In the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

关键词： metabolism therapeutic immunity

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Sirt5 desuccinylates Cdc42 to mediate osteoclastogenesis and bone remodeling in mice

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Genes & Diseases 2024年第3期11卷 75-78页

作者： Yuang Zhanngg Jing Wang Jing Luan Chuanju Liu Yazhou Cui Jinxiang Han Department of Orthopedics The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalJi'nanShandong 250014China Biomedical Sciences College&Shandong Medicinal biotechnology Centre Shandong First Medical University&Shandong Academy of Medical SciencesJi'nanShandong 250117China nhc key laboratory of biotechnology Drugs(Shandong Academy of Medical Sciences) Ji'nanShandong 250117China key Lab for Rare&Uncommon Diseases of Shandong Province Ji'nanShandong250117China Department of Orthopaedic Surgery New York University Grossman School of MedicineNew YorkNY 10003USA Department of Cell Biology New York University Grossman School of MedicineNewYorkNY10016USA

Post-translational modifications(PTMs)play a critical role in bone remodeling,with phosphorylation and acetylation being particularly well characterized.Recently,succinylation,a relatively uncommon PTM on lysine,has received considerable research attention for its influence on several physiological and pathological processes and conditions.1 Several substrates involved in mitochondrial pathways have been validated as substrates for the desuccinylase sirtuin 5(Sirt5),a key regulator of succinylation.2 Bone is one of the most metabolically active organs,but the role of succinylation during bone remodeling is not well characterized.

关键词： remodeling organs media

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Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(Life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen Liujing Huang Bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie Department of Endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State key laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China School of Public Health Xinxiang Medical UniversityXinxiang 453003China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile biotechnology(Shanghai)Co.Ltd. Shanghai 201315China Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China laboratory of Animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Bioland laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle system.However,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains elusive.We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging process.Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total number.Furthermore,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging.Meanwhile,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/myoblasts.The butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and myoblasts.As a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging.Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)

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Zwitterionic ring-opening polymerization of macrocyclic ethyleneoxy-substituted carbonate:Access to cyclic PEG-like polycarbonate

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Chinese Chemical Letters 2024年第3期35卷 282-286页

作者： Jin Huang Jinwen Li Rui Yan Yuanyuan Qu Fengzhen Guo Lei Shen Can-liang Ma Jie Sun Zhenjiang Li Kai Guo State key laboratory of Materials-Oriented Chemical Engineering College of Biotechnology and Pharmaceutical EngineeringNanjing Tech UniversityNanjing 211816China Institute of Nanjing Advanced Biomaterials&Processing Equipment Lishui Economic Development ZoneNanjing 211299China

The innovation in polymer design to rival conventional polyethylene glycol(PEG)is an important approach to achieving a more sustainable society.Here,cyclic PEG-like polycarbonates having high molecular weight(4.4–49.5 kg/mol)were enabled through zwitterionic ring-opening polymerization(ZROP)of macrocyclic carbonates(MCs)mediated by N-heterocyclic carbene(nhc).The thermodynamic behavior of polymerization depends on the ring size of monomers.During this process,the ZROP of 11-membered MC was driven by the change of enthalpy(ΔH_(p))which differed from the ZROP of 14-membered MC driven by the entropic change(ΔS_(p)).Cyclic polycarbonates depicted improved thermostability(T_(d5%)≥204℃)and higher glass transition temperatures(T_(g)>–40℃)in comparison to their linear analogues(T_(d5%)≤185℃,T_(g)~–50℃).In addition,the mechanism of ZROP of MC was addressed through computational study.A distinct mechanism of polymerization distinguishable from the well-known nhc-mediated ZROP of cyclic esters was revealed,where the zwitterion from nucleophilic addition to MC,i.***.tetrahedral intermediate,cannot be ring-opened probably due to the delocalization of negative charge on the carbonate group,but serves as an active center for the polymerization.In comparison to PEG,the attained polymer demonstrated comparable hydrophilic and biocompatible properties,as revealed by the results of contact angle and in vitro cytotoxicity studies,suggesting that cyclic polycarbonate hold the promise as the alternative of PEG.

关键词： Zwitterionic ring-opening polymerization Cyclic polycarbonate Macrocycles Tetrahedral intermediate nhc carbene

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Spontaneous mutations and mutational responses to penicillin treatment in the bacterial pathogen Streptococcus pneumoniae D39

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Marine Life Science & Technology 2024年第2期6卷 198-211页

作者： Wanyue Jiang Tongtong Lin Jiao Pan Caitlyn ERivera Clayton Tincher Yaohai Wang Yu Zhang Xiang Gao Yan Wang Ho‑Ching T.Tsui Malcolm E.Winkler Michael Lynch Hongan Long Institute of Evolution and Marine Biodiversity KLMMEOcean University of ChinaQingdao 266003China laboratory for Marine Biology and biotechnology Laoshan LaboratoryQingdao 266237China Department of Biology Indiana UniversityBloomingtonIN 47405USA School of Mathematics Science Ocean University of ChinaQingdao 266000China State key laboratory of Microbial Technology Microbial Technology InstituteSchool of Life ScienceShandong UniversityQingdao 266237China Biodesign Center for Mechanisms of Evolution Arizona State UniversityTempeAZ 85281USA

Bacteria with functional DNA repair systems are expected to have low mutation rates due to strong natural selection for genomic stability.However,our study of the wild-type Streptococcus pneumoniae D39,a pathogen responsible for many common diseases,revealed a high spontaneous mutation rate of 0.02 per genome per cell division in mutation-accumulation(MA)lines.This rate is orders of magnitude higher than that of other non-mutator bacteria and is characterized by a high mutation bias in the A/T direction.The high mutation rate may have resulted from a reduction in the overall efficiency of selection,conferred by the tiny effective population size in nature.In line with this,S.pneumoniae D39 also exhibited the lowest DNA mismatch-repair(MMR)efficiency among bacteria.Treatment with the antibiotic penicillin did not elevate the mutation rate,as penicillin did not induce DNA damage and S.pneumoniae lacks a stress response pathway.Our findings suggested that the MA results are applicable to within-host scenarios and provide insights into pathogen evolution.

关键词： Neutral evolution Mutation spectrum antibiotics DNA mismatch repair Oxidative damage repair

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Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma

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Journal of Zhejiang University-Science B(Biomedicine & biotechnology) 2024年第1期25卷 83-90页

作者： Zhikun LIU Yichao WU Abid Ali KHAN Lun LU Jianguo WANG Jun CHEN Ningyang JIA Shusen ZHENG Xiao XU key laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou310006China Zhejiang University School of Medicine Hangzhou310058China Department of Radiology Easter Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai200438China Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou310003China nhc key laboratory of Combined Multi-organ Transplantation Hangzhou310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou310022China

Hepatocellular carcinoma(HCC)is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide(Forner et al.,2018;He et al.,2023).Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle(SM)mass that may be age-related or the result of malnutrition in cancer patients(Cruz-Jentoft and Sayer,2019).Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival(Voron et al.,2015;van Vugt et al.,2016).

关键词： cancer patients

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Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2/ZFP36 signal axis

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Journal of Zhejiang University-Science B(Biomedicine & biotechnology) 2024年第5期25卷 422-437页

作者： Xin LI Yanan HU Yueting WU Zuocheng YANG Yang LIU Hanmin LIU Department of Pediatric Pulmonology and Immunology West China Second University HospitalSichuan UniversityChengdu 610041China key laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University) Ministry of EducationChengdu 610041China nhc key laboratory of Chronobiology(Sichuan University) Chengdu 610041China The Joint laboratory for Lung Development and Related Diseases of West China Second University Hospital Sichuan University and School of Life Sciences of Fudan UniversityWest China Institute of Women and Children's HealthWest China Second University HospitalSichuan UniversityChengdu 610041China Sichuan Birth Defects Clinical Research Center West China Second University HospitalSichuan UniversityChengdu 610041China Department of Pediatrics the Third Xiangya HospitalCentral South UniversityChangsha 410013China

Viral myocarditis(VMC)is one of the most common acquired heart diseases in children and teenagers.However,its pathogenesis is still unclear,and effective treatments are lacking.This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes(CMCs)induced by coxsackievirus B3(CVB3).CVB3 was utilized for inducing the VMC mouse model and cellular model.Cardiac echocardiography,left ventricular ejection fraction(LVEF),and left ventricular fractional shortening(LVFS)were implemented to assess the cardiac function.In CVB3-induced VMC mice,cardiac insufficiency was observed,as well as the altered levels of ferroptosis-related indicators(glutathione) peroxidase 4(GPX4),glutathione(GSH),and malondialdehyde(MDA).However,exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)could restore the changes caused by CVB3 stimulation.Let-7a-5p was enriched in hucMSCs-exo,and the inhibitory ffect of hucMSCs-exoa-ie-pmimo on CVB3-induced ferroptosis was higher than that of hucMSCs-exommie N(NC:negative control).Mothers against decapentaplegic homolog 2(SMAD2)increased in the VMC group,while the expression of zinc-finger protein 36(ZFP36)decreased.Let-7a-5p was confirmed to interact with SMAD2 messenger RNA(mRNA),and the SMAD2 protein interacted directly with the ZFP36 protein.Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators.Meanwhile,the levels of GPX4,solute carrier family 7,member 11(SLC7A11),and GSH were lower in the SMAD2 overexpression plasmid(oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group,while those of MDA,reactive oxygen species(ROS),and Fe^(2+)increased.In conclusion,these data showed that ferroptosis could be regulated by mediating SMAD2 expression.Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36,which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.

关键词： Exosome Let-7a-5p Mothers against decapentaplegic homolog 2(SMAD2) Coxsackievirus B3(CVB3) Ferroptosis

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Estimating the Scarlet Fever Epidemics Using a Seasonal Autoregressive Fractionally Integrated Moving Average Model

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Biomedical and Environmental Sciences 2024年第3期37卷 336-340页

作者： WANG Yong Bin XUE Chen Lu ZHOU Pei Ping ZHANG Bing Jie XU Chun Jie Department of Epidemiology and Health Statistics School of Public HealthThe First Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453003HenanChina Beijing key laboratory of Antimicrobial Agents/laboratory of Pharmacology Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Scarlet fever(SF)is a common infectious disease caused by group A streptococcus(GAS)[1].During the 18th and 19th centuries,SF was a significant cause of mortality in children aged 5-15 years worldwide[2].The incidence and fatality rates of SF have decreased remarkably due to the widespread use of effective antibiotics and improvements in diet and sanitation[3].However,the recent resurgence of SF has sparked significant interest in infectious diseases[1,3].Given the insufficient understanding of the triggers that cause SF outbreaks and the absence of available vaccines to prevent GAS infection to date[1],effective prevention and control programs are needed to manage the ongoing spread of SF.

关键词： prevention mortality let

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