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Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2726-2737页

作者： Bo Liu Honghui Liu Pu Han Xiaoyun Wang Chunmei Wang Xinxin Yan Wenwen Lei Ke Xu Jianjie Zhou Jianxun Qi Ruiwen Fan Guizhen Wu Wen-xia Tian George F.Gao Qihui Wang College of Veterinary Medicine Shanxi Agricultural University030801 JinzhongChina CAS Key Laboratory of Pathogen microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)100101 BeijingChina School of Life Sciences Yunnan University650504 KunmingYunnan ProvinceChina NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)102206 BeijingChina Savaid Medical School University of Chinese Academy of Sciences101408 BeijingChina

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its *** suggests that highly conserved epitopes are crucial for the development of neutralizing ***,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its ***-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S *** neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S ***,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus *** to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in *** intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

关键词： doses prevention conserved

Aspergillus niger prolyl endopeptidase in celiac disease

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World Journal of Gastroenterology 2024年第24期30卷 3044-3047页

作者： Marica Colella Concetta Cafiero Raffaele Palmirotta Interdisciplinary Department of Medicine Section of Microbiology and VirologyUniversity of Bari“Aldo Moro”Bari 70124Italy Area of Molecular Pathology Anatomic Pathology UnitFabrizio Spaziani HospitalFrosinone 03100Italy

We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of *** disease is a well-recognized systemic autoimmune *** genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of *** that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to *** aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small *** study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing *** study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.

关键词： Celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

Evidence supporting the relationship between maternal asthma and risk for autism spectrum disorders

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Neural Regeneration research 2025年第4期20卷 1101-1102页

作者： Hadley Osman Paul Ashwood Department of Medical microbiology and Immunology and the M.I.N.D.InstituteUniversity of California at DavisSacramentoCAUSA

During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing *** has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the *** is characterized by increased repetitive and stereotyped behaviors and decreased *** of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ***,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased *** allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.

关键词： disorders epidemiology fetus

Beyond microbial carbon use efficiency

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National Science Review 2024年第4期11卷 33-35页

作者： Ke-Qing Xiao Chao Liang Zimeng Wang Jingjing Peng Yao Zhao Ming Zhang Mingyu Zhao Shuiqing Chen Yong-Guan Zhu Caroline L.Peacock State Key Lab of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of Sciences University of Chinese Academy of Sciences Institute of Applied Ecology Chinese Academy of Sciences Department of Environmental Science and Engineering Fudan University College of Resources and Environmental Sciences China Agricultural University State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental Sciences State Key Laboratory of Agricultural microbiology College of Resources and Environment Huazhong Agricultural University Key Laboratory of Cenozoic Geology and Environment Institute of Geology and Geophysics Chinese Academy of Sciences School of Earth and Environment University of Leeds

Microbial carbon use efficiency (CUE)is defined as the proportion of microbial biomass growth C versus substrate C uptake, and thus provides a useful measure of microbially driven accumulation and loss of soil organic carbon (SOC)[1]. In a recent study published in Nature [2],the authors used a data-driven machinelearning approach to conclude that CUE promotes global SOC storage based on a positive correlation between CUE and SOC content and that, based on sensitivity analysis, CUE is at least four times as important as six other evaluated factors,namely plant C inputs, C input allocation, non-microbial C transfer, substrate decomposability, environmental modifications and vertical transport.

关键词： SOIL-CARBON ORGANIC-MATTER

Commentary on“Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells”

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research 2024年第3期6卷 621-623页

作者： Chen Li Craig N.Morrell Aab Cardiovascular research Institute University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Pharmacology and Physiology University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA Department of microbiology and Immunology University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Pathology and Laboratory Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA.

Platelets have long been studied for their roles in hemostasis and vascular injury repair. However, there is a continually evolving and deepening understanding that platelets initiate and regulate responses to tissue injury and pathogens, leading to platelets now being considered immune modulatory cells [1]. Platelets actively participate in host immune responses directly through pathogen engulfing and killing, or by regulating both innate and adaptive immune responses to infection or tissue injury [2]. Activated platelets promote inflammatory responses to tissue injury or infection by direct contact dependent interactions with immune cells and through indirect interactions via released soluble factors. However, mice that are deficient in platelets have skewed T helper cell differentiation [3] and increased vascular permeability [4], implying poorly defined roles for platelets in maintaining healthy immune homeostasis.

关键词： Platelet homeostasis Immune

Diverse genotypes of norovirus genogroup I and II contamination in environmental water in Thailand during the COVID-19 outbreak from 2020 to 2022

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Virologica Sinica 2024年第4期39卷 556-564页

作者： Kattareeya Kumthip Pattara Khamrin Aksara Thongprachum Rungnapa Malasao Arpaporn Yodmeeklin Hiroshi Ushijima Niwat Maneekarn Department of microbiology Faculty of MedicineChiang Mai UniversityChiang MaiThailand Center of Excellence(Emerging and Re-emerging Diarrheal Viruses) Chiang Mai UniversityChiang MaiThailand Faculty of Public Health Chiang Mai UniversityChiang MaiThailand Department of Community Medicine Faculty of MedicineChiang Mai UniversityChiang MaiThailand Department of Pathology and microbiology Nihon University School of MedicineTokyoJapan

Noroviruses(NoVs)are the most significant viral pathogens associated with waterborne and foodborne outbreaks of nonbacterial acute gastroenteritis in humans *** study aimed to investigate the prevalence and diversity of NoVs contaminated in the environmental water in Chiang Mai,Thailand.A total of 600 environmental water samples were collected from ten sampling sites in Chiang Mai from July 2020 to December *** presence of NoV genogroups I(GI),GII,and GIV were examined using real-time RT-PCR *** genotype of the virus was determined by nucleotide sequencing and phylogenetic *** results showed that NoV GI and GII were detected at 8.5%(51/600)and 11.7%(70/600)of the samples tested,***,NoV GIV was not detected in this *** circulated throughout the year,with a higher detection rate during the winter *** NoV GI genotypes(GI.1-GI.6)and eight NoV GII genotypes(GII.2,GII.3,GII.7,GII.8,GII.10,GII.13,GII.17,and GII.21)were *** 121 NoV strains detected,GII.17 was the most predominant genotype(24.8%,30 strains),followed by GII.2(21.5%,26 strains),GI.3(17.4%,21 strains),and GI.4(16.5%,20 strains).Notably,NoV GII.3,GII.7,GII.8,and GII.10 were detected for the first time in water samples in this *** study provides insight into the occurrence and seasonal pattern of NoV along with novel findings of NoV strains in environmental water in Thailand during the COVID-19 *** findings emphasize the importance of further surveillance studies to monitor viral contamination in environmental water.

关键词： Detection Environmental water Norovirus(NoVs) Wastewater Thailand

The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling Alistair James Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna Jordan Mathias Jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher Joseph Schofield Timothy Walsh Department of Biology&Ineos Oxford Institute for Antimicrobial research University of OxfordOxford OX13REUK Chemistry research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

Soil microbial ecology through the lens of metatranscriptomics

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Soil Ecology Letters 2024年第3期6卷 1-15页

作者： Jingjing Peng Xi Zhou Christopher Rensing Werner Liesack Yong-Guan Zhu State Key Laboratory of Nutrient Use and Management College of Resources and Environmental SciencesNational Academy of Agriculture Green DevelopmentKey Laboratory of Plant-Soil InteractionsMinistry of EducationChina Agricultural UniversityBeijing 100193China Institute of Environmental microbiology College of Resource and EnvironmentFujian Agriculture and Forestry UniversityFuzhou 350002China Max Planck Institute for Terrestrial microbiology Marburg 35043Germany State Key Laboratory of Urban and Regional Ecology Research Centre for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Key Laboratory of Urban Environment and Health Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China

Metatranscriptomics is a cutting-edge technology for exploring the gene expression by,and functional activities of,the microbial community across diverse ecosystems at a given time,thereby shedding light on their metabolic responses to the prevailing environmental *** double-RNA approach involves the simultaneous analysis of rRNA and mRNA,also termed structural and functional *** contrast,mRNA-centered metatranscriptomics is fully focused on elucidating community-wide gene expression profiles,but requires either deep sequencing or effective rRNA *** this review,we critically assess the challenges associated with various experimental and bioinformatic strategies that can be applied in soil microbial ecology through the lens of functional *** particular,we demonstrate how recent methodological advancements in soil metatranscriptomics catalyze the development and expansion of emerging research fields,such as rhizobiomes,antibiotic resistomes,methanomes,and *** review provides a framework that will help to design advanced metatranscriptomic research in elucidating the functional roles and activities of microbiomes in soil ecosystems.

关键词： metatranscriptomics mRNA MAGs rhizobiont resistome virome

Multi-systemic melioidosis

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World Journal of Clinical Cases 2024年第28期12卷 6151-6154页

作者： Basavraj S Nagoba Shree V Dhotre Abhijit S Rayate Sachin S Mumbre Pradnya S Dhotre Department of microbiology Maharashtra Institute of Medical Sciences and Research(Medical College)Latur 413531India Department of microbiology Ashwini Rural Medical CollegeSolapur 413001India Department of Surgery Maharashtra Institute of Medical Sciences and Research(Medical College)Latur 413531India Department of Community Medicine Ashwini Rural Medical CollegeSolapur 413006India Department of Biochemistry Ashwini Rural Medical CollegeSolapur 413001India

This editorial is a commentary on the article by Ni et al,which was published in the World Journal of Clinical *** article discusses the diagnostic and therapeutic challenges of melioidosis caused by Burkholderia *** case study highlights a rare instance of multisystemic melioidosis in a female patient who did not have a travel history,emphasizing the significance of recognizing this condition in non-endemic *** complexities and therapeutic strategies are addressed,emphasizing the need for heightened clinical suspicion,comprehensive evaluation,and multidisciplinary *** editorial delves into the clinical presentation,diagnostic dilemmas,therapeutic approaches,and their implications for patient care in managing multi-systemic melioidosis.

关键词： Melioidosis Burkholderia pseudomallei Multi-systemic Diagnosis Treatment