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Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

Cellular & Molecular immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan Shuaixin Gao Thomas S.Fulford Adam P.Uldrich Catherine C.L Wong Wensheng Wei Biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics Research Peking University Health Science CenterPeking University100191BeijingChina Department of microbiology and immunology at the Peter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia State key laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

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The protective effects of fermented vinegar on acute alcohol-induced hepatic and neuro-toxicity by regulating ethanol metabolism and gut microbiota

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Food Science and Human Wellness 2024年

作者： Yuan Meng Yunfan Liu Ting Xia Beibei Geng Yinglei Tian Hailong Cao Jin Yan Xiaoqi Pang Kai Liang Yufeng Yan Min Wang State key laboratory of Food Nutrition and Safety key laboratory of Industrial Fermentation microbiology College of Biotechnology Tianjin University of Science and Technology Department of Gastroenterology and Hepatology General Hospital Tianjin Medical University National key Clinical Specialty Tianjin Institute of Digestive Diseases Tianjin key laboratory of Digestive Diseases Shanxi Provincial key laboratory for Vinegar Fermentation Science and Engineering Shanxi Zilin Vinegar Industry Co. Ltd.

Alcohol abuse constitutes a significant health hazard， leading to various organ damage， notably the liver and brain. Shanxi aged vinegar (SAV) is one of the famous fermented and functional foods containing a variety of bioactive ingredients with beneficial effects on the human body. This study aimed to explore the potential protective effect of SAV in alleviating acute alcohol intoxication (AAI) in mice. It was found that SAV at 2.5 mg/kg BW effectively ameliorated the decline in behavioral abilities following alcohol consumption， characterized by a shortened sobering period. SAV reduces alcohol-induced liver damage by inhibiting hepatic function enzymes and oxidative stress levels. Additionally， SAV mitigated the overactivation of microglia and the downregulation of neurotransmitter levels (AchE， 5-HT， and DA)， thereby reducing ethanol-induced brain damage. Meanwhile， SAV significantly decreased concentrations of alcohol and acetaldehyde in the blood and increased ADH and ALDH activities in the liver， indicating enhancement of ethanol metabolism. Moreover， we found that some gut microbiota including Verrucomicrobiota， Akkermansia， and Enterococcus were downregulated after SAV treatment in mice with AAI. These bacteria showed a negative correlation with anti-oxidative markers (GSH and CAT) and enzymes related to ethanol metabolism pathways (ADH and ALDH)， and a positive correlation with hepatic function markers (ALT， AST， and MDA)， alcohol metabolites (alcohol and acetaldehyde) and neurotransmitters (AchE， 5-HT， and DA). However， Bacteroidota， norank＿f＿Muribaculaceae， and Alistipes exhibited the opposite direction. These findings suggest that SAV possesses protective effects against hepatic and neuro-toxicity， and could be a potential functional food for AAI prevention.

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Epigenetic modification in liver fibrosis:Promising therapeutic direction with significant challenges ahead

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1009-1029页

作者： Runping Liu Yajing Li Qi Zheng Mingning Ding Huiping Zhou Xiaojiaoyang Li School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 102400China School of Life Sciences Beijing University of Chinese MedicineBeijing 102400China Department of microbiology and immunology Virginia Commonwealth UniversityRichmondVA 22460USA

Liver fibrosis,characterized by scar tissue formation,can ultimately result in liver failure.It’s a major cause of morbidity and mortality globally,often associated with chronic liver diseases like hepatitis or alcoholic and non-alcoholic fatty liver diseases.However,current treatment options are limited,highlighting the urgent need for the development of new therapies.As a reversible regulatory mechanism,epigenetic modification is implicated in many biological processes,including liver fibrosis.Exploring the epigenetic mechanisms involved in liver fibrosis could provide valuable insights into developing new treatments for chronic liver diseases,although the current evidence is still controversial.This review provides a comprehensive summary of the regulatory mechanisms and critical targets of epigenetic modifications,including DNA methylation,histone modification,and RNA modification,in liver fibrotic diseases.The potential cooperation of different epigenetic modifications in promoting fibrogenesis was also highlighted.Finally,available agonists or inhibitors regulating these epigenetic mechanisms and their potential application in preventing liver fibrosis were discussed.In summary,elucidating specific druggable epigenetic targets and developing more selective and specific candidate medicines may represent a promising approach with bright prospects for the treatment of chronic liver diseases.

关键词： Liver fibrosis Epigenetics regulation DNA methylation Histone acetylation Histone methylation mRNA methylation Non-coding RNA Drug development

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The role of corneal endothelium in macular corneal dystrophy development and recurrence

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Science China(Life Sciences) 2024年第2期67卷 332-344页

作者： Bi-Ning Zhang Benxiang Qi Chunxiao Dong Bin Zhang Jun Cheng Xin Wang Suxia Li Xiaoyun Zhuang Shijiu Chen Haoyun Duan Dewei Li Sujie Zhu Guoyun Li Yihai Cao Qingjun Zhou Lixin Xie Eye Institute of Shandong First Medical University Qingdao Eye Hospital of Shandong First Medical UniversityQingdao 266071China State key laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyQingdao 266071China School of Ophthalmology Shandong First Medical UniversityQingdao 250021China Department of Medicine Qingdao UniversityQingdao 266071China Eye Institute of Shandong First Medical University Eye Hospital of Shandong First Medical University(Shandong Eye Hospital)Jinan 250021China Department of Ophthalmology School of Clinical MedicineWeifang Medical UniversityWeifang 261072China Institute of Translational Medicine College of MedicineQingdao UniversityQingdao 266071China key laboratory of Marine Drugs of Ministry of Education Shandong Provincial Key Laboratory of Glycoscience and GlycotechnologySchool of Medicine and PharmacyOcean University of ChinaQingdao 266071China laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266071China Department of microbiology Tumor and Cell BiologyBiomedicumKarolinska InstitutetStockholm 17177Sweden

Macular corneal dystrophy(MCD)is a progressive,bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6(CHST6).Corneal transplantation is the ultimate therapeutic solution for MCD patients.Unfortunately,postoperative recurrence remains a significant challenge.We conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty(PKP)or deep anterior lamellar keratoplasty(DALK).Our results revealed that the recurrence rate was nearly three times higher in the DALK group(39.13%,9/23 eyes)compared with the PKP group(10.89%,11/101 eyes),suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative recurrence.Our experimental data confirmed the robust m RNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse endothelium.Selective knockdown of wild-type Chst5 in mouse corneal endothelium(AC^(siChst5)),but not in the corneal stroma,induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD patients.Mice carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD,along with corneal endothelial abnormalities.Intracameral injection of wild-type Chst5 rescued the corneal impairments in AC^(siChst5)mice and retarded the disease progression in Chst5 mutant mice.Overall,our study provides new mechanistic insights and therapeutic approaches for MCD treatment by highlighting the role of corneal endothelium in MCD development.

关键词： macular corneal dystrophy recurrence corneal endothelium keratan sulfate penetrating keratoplasty

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Ability of Helicobacter pylori to internalize into Candida

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World Journal of Gastroenterology 2024年第16期30卷 2281-2284页

作者： Zheng-Hong Chen Jian-Chao Sun Ting-Xiu Yang Gu-Zhen Cui key laboratory of microbiology and Parasitology of Education Department of Guizhou Guizhou Medical UniversityGuiyang 561113Guizhou ProvinceChina key laboratory of Endemic and Ethnic Diseases of Ministry of Education Guizhou Medical UniversityGuiyang 561113Guizhou ProvinceChina Joint laboratory of Helicobacter Pylori and Intestinal Microecology Affiliated Hospital of Guizhou Medical UniversityGuiyang 550009Guizhou ProvinceChina Department of Quality Control Guizhou Provincial Center for Clinical LaboratoryGuiyang 550002Guizhou ProvinceChina Department of Hospital Infection and Management Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina

The following are our views regarding the“letter to the editor”(Helicobacter is preserved in yeast vacuoles!Does Koch’s postulates confirm it?)by Alipour and Gaeini,and the response“letter to the editor”(Candida accommodates nonculturable Helicobacter pylori in its vacuole-Koch’s postulates aren’t applicable)by Siavoshi and Saniee.Alipour and Gaeini rejected the methods,results,discussion,and conclusions summarized in a review article by Siavoshi and Saniee.The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori(H.pylori)to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse,transporting potentially infectious H.pylori into the stomach of humans.

关键词： Helicobacter pylori Candida yeast Intracellular presence Helicobacter pylori-specific gene Helicobacter pylori transmission

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Efficient inhibition of SARS-CoV-2 emerging EG.5,EG.5.1 and BA.2.86 variants by fusion inhibitor HY3000 peptide

hLife

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hLife 2024年第1期2卷 43-46页

作者： Lili Wu Anqi Zheng Yangming Tang Xiaoyun Wang Yue Gao Wenwen Lei Guizhen Wu Qihui Wang George Fu Gao cas key laboratory of Pathogen microbiology and immunology Institute of MicrobiologyChinese Academy of SciencesBeijingChina University of the Chinese Academy of Sciences BeijingChina Hybio Pharmaceutical Co. Ltd.GuangdongChina College of Life Science Hebei UniversityHebeiChina NHC key laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Chinese Center for Disease Control and Prevention BeijingChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to pose a significant threat to the world,as it continually evolves and gives rise to multiple variants and sub-variants.Recently,the Omicron EG.5 linage,which was first detected in Indonesia on 17 February 2023,has raised concerns due to its increased prevalence and extended immune escape properties,according to the risk analysis by the World Health Organization(WHO)[1].As of 3 October 2023,EG.5 and its sub-linages have been reported in 83 countries with shared 49,008 genome sequences in GISAID database(https://***/hcov19-variants/).EG.5 has become the dominant strain in the United States according to Centers for Disease Control and Prevention(CDC),accounting for 29.4%of SARS-CoV-2 infections(https://covid.***.gov/covid-data-tracker/#variant-proportions).

关键词： acute respiratory variants

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LonP1 Links Mitochondria–ER Interaction to Regulate Heart Function

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Research 2024年第1期2023卷 595-609页

作者： Yujie Li Dawei Huang Lianqun Jia Fugen Shangguan Shiwei Gong Linhua Lan Zhiyin Song Juan Xu Chaojun Yan Tongke Chen Yin Tan Yongzhang Liu Xingxu Huang Carolyn K.Suzuki Zhongzhou Yang Guanlin Yang Bin Lu The Affiliated Nanhua Hospital and School of Basic Medical Sciences Hengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China School of laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhouZhejiang 325035China National Health Commission key laboratory of Birth Defect Research and Prevention Hunan Provincial Maternal and Child Health Care HospitalChangshaHunan 410008China key laboratory of Ministry of Education for TCM Viscera-State Theory and Applications Ministry of Education of ChinaLiaoning University of Traditional Chinese MedicineShenyangLiaoning 110847China key laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Hubei key laboratory of Cell Homeostasis College of Life SciencesWuhan UniversityWuhanHubei 430072China Nanjing Maternity and Child Health Care Hospital Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical UniversityNanjing 210004China Animal Center Wenzhou Medical UniversityWenzhouZhejiang 325035China Department of Cardiology The First Affiliated Hospital of University of South ChinaHengyangHunanChina School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China Department of microbiology Biochemistry and Molecular GeneticsNew Jersey Medical School-RutgersThe State University of New JerseyNewarkNJUSA State key laboratory of Pharmaceutical Biotechnology Department of CardiologyNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical School and MOE Key Laboratory of Model Animal for Disease StudyModel Animal Research CenterNanjing UniversityNanjing 210061China

Interorganelle contacts and communications are increasingly recognized to play a vital role in cellular function and homeostasis.In particular,the mitochondria–endoplasmic reticulum(ER)membrane contact site(MAM)is known to regulate ion and lipid transfer,as well as signaling and organelle dynamics.However,the regulatory mechanisms of MAM formation and their function are still elusive.Here,we identify mitochondrial Lon protease(LonP1),a highly conserved mitochondrial matrix protease,as a new MAM tethering protein.The removal of LonP1 substantially reduces MAM formation and causes mitochondrial fragmentation.Furthermore,deletion of LonP1 in the cardiomyocytes of mouse heart impairs MAM integrity and mitochondrial fusion and activates the unfolded protein response within the ER(UPR^(ER)).Consequently,cardiac-specific LonP1 deficiency causes aberrant metabolic reprogramming and pathological heart remodeling.These findings demonstrate that LonP1 is a novel MAM-localized protein orchestrating MAM integrity,mitochondrial dynamics,and UPR^(ER),offering exciting new insights into the potential therapeutic strategy for heart failure.

关键词： offering programming insight

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Preparation and immunoprotective effects of a virus-like particle candidate vaccine of the dominant epidemic D3 genotype coxsackievirus A6 in China

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Biosafety and Health 2024年第1期6卷 28-34页

作者： Xiaoliang Li Xizhu Xu Jichen Li Huanhuan Lu Congcong Wang Rui Wang Jinbo Xiao Ying Liu Yang Song Jingdong Song Qiang Sun Yong Zhang Department of Public Health and Health Administration Shandong First Medical UniversityJinan 250117China National key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID) National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Polio laboratory WHO WPRO Regional Polio Reference LaboratoryNational Health Commission Key Laboratory for BiosafetyNational Health Commission Key Laboratory for Medical VirologyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBejing 102206China Department of Medical microbiology Weifang Medical UniversityWeifang 261053China

Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).Viral‐like particle(VLP)vaccines represent a potential candidate vaccine to prevent HFMD.This study collected Anti‐CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a VLPs.The neutralizing antibody levels were compared against the representative 14‐JX2018(D3a)and N4‐YN2015(D3b)strains between the antisera of different immune pathways.The immunoprotective effect of anti‐CVA6 D3a VLPs against these strains was monitored using pathological sections and immuno-histochemical results of lung and skeletal muscle tissues in seven‐day‐old Institute of Cancer Research(ICR)mice.Immunological protection against different branches of viruses was evaluated in 7‐day‐old(serum passive immune protection)and 14‐day‐old(VLPs active immune protection)neonatal ICR mice models.Serum‐neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14‐JX2018 than against N4‐YN2015.Furthermore,these levels were significantly higher with abdominal injection than intramuscular injection.The immunized serum of 7‐day‐old ICR mice inoculated three times was 100%protected against CVA6 D3a 14‐JX2018(lethal titer:106.25 TCID 50)and CVA6 D3b N4‐YN2015(lethal titer:105.25TCID 50)fatal attacks,respectively.For ICR mice that have completed two active immunizations for 14 days,both CVA6 D3a 14‐JX2015(challenge titer:108.25 TCID 50)and CVA6 D3b N4‐YN2015(challenge titer:107.25 TCID 50)were used for the challenge,and the mice were able to survive.Overall,the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6,as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.

关键词： Coxsackievirus A6 D3 genotype Virus‐like particle Immunoprotective effect

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Plants affect the horizontal transmission of a new densovirus infecting the green peach aphid Myzus persicae by modulating honeydew production

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Insect Science 2024年第1期31卷 236-254页

作者： Ya Guo Yani Zhao Yang Yang Yahong Zhang Yuying Li Honggang Tian Tong-Xian Liu Zhaofei Li State key laboratory of Crop Stress Biology for Arid Areas Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of AgricultureCollege of Plant ProtectionNorthwest A&F UniversityYanglingChina Institute of Entomology and Institute of Plant Health&Medicine Guizhou UniversityGuiyangChina

In a tritrophic context of plant-insect-entomopathogen,plants play important roles in modulating the interaction of insects and their pathogenic viruses.Currently,the influence of plants on the transmission of insect viruses has been mainly studied on baculoviruses and some RNA viruses,whereas the impact of plants on other insect viruses is largely unknown.Here,we identified a new densovirus infecting the green peach aphid Myzus persicae and tested whether and how host plants influence the transmission of the aphid densovirus.The complete single-stranded DNA genome of the virus,M.persicae densovirus 2,is 5727 nt and contains inverted terminal repeats.Transcription and phylogenetic analysis indicated that the virus was distinct from other a few identified aphid densoviruses.The virus abundance was detected highly in the intestinal tract of aphids,compared with the lower level of it in other tissues including head,embryo,and epidermis.Cabbage and pepper plants had no obvious effect on the vertical transmission and saliva-mediated horizontal transmission of the virus.However,the honeydew-mediated horizontal transmission among aphids highly depended on host plants(65%on cabbages versus 17%on peppers).Although the virus concentration in the honeydew produced by aphids between 2 plants was similar,the honeydew production of the infected aphids reared on peppers was dramatically reduced.Taken together,our results provide evidence that plants influence the horizontal transmission of a new densovirus in an aphid population by modulating honeydew secretion of aphids,suggesting plants may manipulate the spread of an aphid-pathogenic densovirus in nature.

关键词： aphids densovirus host plants MpDV2 Myzus persicae transmission

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Blood group-gut microbiome–health axis gains further support from landmark multi-omics study in swines

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Science China(Life Sciences) 2022年第11期65卷 2338-2340页

作者： Jiejing Wang Jun Wang cas key laboratory of pathogenic microbiology and immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China

Research into gut microbiome is one of the most productive areas of life sciences in the last decade,revealing great potential for both fundamental and translational researches.The effects of microbiota on host immuni... 详细信息

关键词： Blood metabolism immunity

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