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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

Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice

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Animal Models and Experimental Medicine 2024年第1期7卷 77-81页

作者： Tatsushi Mutoh Ryota Tochinai Hiroaki Aono Masayoshi Kuwahara Yasuyuki Taki Tatsuya Ishikawa Department of Surgical Neurology Research Institute for Brain and Blood VesselsAkita Cerebrospinal and Cardiovascular CenterAkitaJapan Department of Aging Research and Geriatric Medicine Institute of DevelopmentAging and CancerTohoku UniversitySendaiJapan Department of veterinary Pathophysiology and Animal Health Graduate School of Agriculture and Life SciencesThe University of TokyoTokyoJapan

The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are ***,we introduce a simple procedure for se-lecting a mouse model of diffuse *** was induced in 24 mice using a standard filament perforation *** confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura *** CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.

关键词： cisterna magna clot distribution filament perforation mouse model subarachnoid hemorrhage

Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang Haitao Niu William Tse Hai-Bin Ruan Helmut Dolznig Thomas Knosel Friedrich Karl-Heinz Madeleine Themanns Jiang Wang Mingquan Song Lee Denson Lukas Kenner Richard Moriggl Yi Zheng Xiaonan Han Division of Hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer Genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA Division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s Hospital of Fudan University Shanghai 201102China school of Medicine Jinan UniversityGuangzhouGuangdong 510632China Laboratory Animal science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of Medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistry II University Hospital JenaJena 07743Germany Laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann Institute for Cancer Research Vienna 1090Austria Medical University of Vienna Vienna 1040Austria Institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria Division of Experimental Hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

Nitrate reduction capacity of the oral microbiota is impaired in periodontitis:potential implications for systemic nitric oxide availability

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International Journal of Oral science 2024年第1期16卷 52-61页

作者： Bob T.Rosier William Johnston Miguel Carda-Diéguez Annabel Simpson Elena Cabello-Yeves Krystyna Piela Robert Reilly Alejandro Artacho Chris Easton Mia Burleigh Shauna Culshaw Alex Mira Department of Genomics and Health FISABIO FoundationCenter for Advanced Research in Public HealthValenciaSpain Department of Biological and Biomedical sciences Glasgow Caledonian UniversityGlasgowUK Oral sciences University of Glasgow Dental SchoolSchool of MedicineDentistry and NursingCollege of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowUK Sport and Physical Activity Research Institute University of the West of ScotlandBlantyreScotland Instituto de Biomedicina de Valencia Consejo Superior de Investigaciones Científicas(IBV-CSIC)ValenciaSpain CIBER Center for Epidemiology and Public Health MadridSpain

The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity(NRC)and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitratereducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals(P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate(a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment(P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria(P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.

关键词： impaired intake nitrate

Exploration of Ideological and Political Education in veterinary Microbiology Experimental Technology

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Journal of Contemporary Educational Research 2024年第9期8卷 40-46页

作者： Jiedan Liao school of Animal science and Technology Foshan UniversityFoshan 528225Guangdong ProvinceChina

The veterinary microbiology experimental course plays a key role in education and practice,integrating“knowledge,skills,and qualities”into the talent cultivation *** syllabus has been revised to emphasize the course’s ideological and political education *** extraction of ideological and political elements focuses on developing a curriculum that includes ideological and political teaching materials and cases,ensuring coherence across classroom teaching,social practice,and online *** organically integrating ideological and political elements within stories,along with professional knowledge,operational skills,and social practice,the course aims to enhance the appeal and effectiveness of ideological and political education in the experimental course.

关键词： veterinary Microbiology Experimental Technology Ideological and political education Exploration

Hybrid Teaching Reform of veterinary Microbiology Based on the Combination of Virtual Simulation and Problem-Based Learning

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Journal of Contemporary Educational Research 2024年第9期8卷 1-9页

作者： Jiedan Liao school of Life science and Engineering Foshan UniversityFoshan 528225Guangdong ProvinceChina

The veterinary Microbiology course is centered around the diagnosis and testing of pathogenic microorganisms,with the core value of“moral education and character development.”It reconstructs multidimensional teaching resources by integrating disciplinary achievements with clinical cases and implements a hybrid teaching approach combining virtual simulation and problem-based learning(PBL)through the“three stages+four models+three reflections”***-qualification teachers employ various teaching methods,create a“six-in-one”model for ideological and political education,and conduct formative assessments based on the principles of diversified objectives and process *** hybrid teaching reform addresses issues such as fragmented knowledge,insufficient class hours,weak animal disease diagnostic abilities among students,limited application and expansion of knowledge points,and students’lack of proactive critical thinking *** application of hybrid teaching has shown significant advantages and effectiveness,providing a reference for teaching reform in similar microbiology courses.

关键词： veterinary Microbiology Hybrid teaching Virtual simulation Problem-based learning Teaching reform

Research on the Strategic Path of veterinary Medicine Serving Rural Revitalization in Agriculture-Related Universities

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Journal of Contemporary Educational Research 2024年第5期8卷 65-73页

作者： Jiedan Liao school of Life science and Engineering Foshan UniversityFoshan 528225Guangdong ProvinceChina

Local agriculture-related universities must have certain regional advantages,advantages of agricultural characteristics,human resources,and science and technology in the process of implementing the rural revitalization *** literature research and investigation methods,combined with the experience of colleges and universities,the veterinary discipline of rural science and technology correspondent and technology yard,this study discusses our veterinary discipline in education teaching practice and talent training mode innovation,improving the quality of talent training and study on the strategic path of united front service for rural revitalization.

关键词： veterinary medicine Rural revitalization Path research

Honey vesicle-like nanoparticles protect aged liver from non-alcoholic steatohepatitis

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3661-3679页

作者： Baolong Liu Phuong Linh Nguyen Han Yu Xingzhi Li Huiren Wang Tram Gia Bao Nguyen Prakash Kumar Sahoo Meghna Sur Jay Reddy Sarah Sillman Stephen D.Kachman Bara Altartouri Guoqing Lu Sathish Kumar Natarajan Mahesh Pattabiraman Jiujiu Yu Department of Nutrition and Health sciences University of Nebraska-LincolnLincolnNE 68583USA Shaanxi Key Laboratory of Molecular Biology for Agriculture College of Animal Science and TechnologyNorthwest A&F UniversityYangling 712100China Department of Nutrition Case Western Reserve UniversityClevelandOH 44106USA school of veterinary Medicine and Biomedical sciences University of Nebraska-LincolnLincolnNE 68583USA Department of Statistics University of Nebraska-LincolnLincolnNE 68583USA Center for Biotechnology University of Nebraska-LincolnLincolnNE 68588USA Department of Biology University of Nebraska OmahaOmahaNE 68182USA Department of Chemistry University of Nebraska-KearneyKearneyNE 68849USA

Non-alcoholic steatohepatitis(NASH),an advanced form of non-alcoholic fatty liver disease(NAFLD),has emerged as the leading cause of liver failure and related ***,no medication is specifically approved to treat NAFLD or *** we report that oral administration of honey vesiclelike nanoparticles(H-VLNs)to naturally aged mice protects the liver from NASH development.H-VLNs are dominantly taken up by Kupffer cells in the liver and suppress hepatic chronic inflammation and further development of fibrosis and nodule formation in aged *** their reported antiinflammasome function,H-VLNs are found to inhibit the transcriptional activities of C-JUN and nuclear factor-kappa B(NF-κB).MicroRNAs miR5119 and miR5108 and phenolic compound luteolin in H-VLNs are identified in suppressing both the C-JUN and NF-kB ***,oral intake of H-VLNs represents a promising new user-friendly modality to prevent the development of NASH.

关键词： Honey Extracellular vesicles Exosomes Nanoparticles microRNAs Aging Inflammation Non-alcoholic steatohepatitis

Zoonotic human liver flukes,a type 1 biocarcinogen,in freshwater fishes:genetic analysis and confirmation of molluscan vectors and reservoir hosts in Bangladesh

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Infectious Diseases of Poverty 2024年第3期13卷 73-88页

作者： Sharmin Shahid Labony Md.Abdul Alim Muhammad Mehedi Hasan Md.Shahadat Hossain Sharmin Akter Joydeep Paul Thahsin Farjana Md.Haydar Ali Mohammad Zahangir Alam Takeshi Hatta Hayato Kawada Keiko Mizutani Naotoshi Tsuji null Anisuzzaman Department of Parasitology Faculty of Veterinary ScienceBangladesh Agricultural UniversityMymensingh 2202Bangladesh Department of Fisheries Technology Faculty of FisheriesBangladesh Agricultural UniversityMymensingh 2202Bangladesh Department of Biotechnology School of Life Sciences&BiotechnologyAdamas UniversityBarasat-Barrackpore RdJagannathpurKolkataWest Bengal 700126India Department of Pathology and Parasitology Hajee Mohammad Danesh Science and Technology UniversityDinajpur 5200Bangladesh Department of Parasitology and Tropical Medicine Kitasato University School of Medicine1-15-1 KitasatoMinamiSagamiharaKanagawa 252-0374Japan Department of Molecular and Cellular Parasitology Kitasato University Graduate School of Medical Sciences1-15-1 KitasatoMinamiSagamiharaKanagawa 252-0373Japan

Background Opisthorchiid flukes,particularly Opisthorchis viverrini,Opisthorchis felineus,Clonorchis sinensis,and Metorchis *** the most common fish-borne zoonotic human liver flukes(hLFs).Liver fluke infections are more prevalent in resource-deprived and underprivileged *** herein estimated the prevalence of the metacercariae(MC)of major hLFs in common large freshwater fishes(lFWF)marketed for human consumption from some selected areas of Bangladesh along with detection of their molluscan vectors and *** The current status of fish-borne zoonotic hLF infections in lFWF was investigated along with their molluscan vectors and mammalian reservoir hosts in Mymensingh and Kishoreganj in Bangladesh from July 2018-June 2022 using conventional and multiple molecular techniques,such as PCR,PCR-restriction fragment length polymorphism(RFLP),sequencing,and bioinformatic *** infection rate of fishes was analyzed using the Z-test and the loads of MC were compared using the chi-squared(χ^(2))*** The MC of ***,Opisthorchis spp.,and Metorchis *** detected in 11 species of common and popular *** lFWF,the estimated prevalence was 18.7%and the mean load was 137.4±149.8 MC per 100 g of *** prevalence was the highest(P0.05)distributed between the head and body of *** infection rate was slightly higher in cultured(19.6%)*** MC of ***,***,***,and Metorchis orientalis in fishes were confirmed using PCR,PCR-RFLP and *** cercariae of opisthorchiid(Pleurolophocercus cercariae)flukes were only recovered from Bithynia spp.(3.9%,42 out of 1089).The ova of hLFs from dogs(4.3%,5 out of 116)and cats(6.0%,6 out of 100),and adult flukes(***)from ducks(41.1%113 out of 275)were *** The MC of

关键词： Human liver fluke Freshwater fish Molluscan vector Reservoir host Bangladesh