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Journal of Genetics and Genomics 2022年第4期49卷 338-349页

作者： Tingting Zhu Linqiang Zhang Chengbin Li Xiaoqiong Tan Jing Liu Huiqin Li Qijing Fan Zhiguo Zhang Mingfeng Zhan Lin Fu Jinbo Luo Jiawei Geng Yingjie Wu Xiaoju Zou Bin Liang Key Laboratory of animal models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of SciencesKunmingYunnan 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China center for Life Sciences School of Life SciencesYunnan UniversityKunmingYunnan 650091China School of Traditional Chinese Medicine Yunnan University of Chinese MedicineKunmingYunnan 650500China Infectious Diseases Department and Hepatic Diseases Department The First People’s Hospital of Yunnan ProvinceKunmingYunnan 650034China Infectious Diseases Department and Hepatic Diseases Department The Affiliated Hospital of Kunming University of Science and TechnologyKunmingYunnan 650034China School of Laboratory animal&Shandong Laboratory animal center Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250021China Institute for Genome engineered animal models of Human Diseases National Center of Genetically Engineered Animal Models for International ResearchLiaoning Provence Key Lab of Genome Engineered Animal Models Dalian Medical UniversityDalianLiaoning 116044China

Liver fibrosis is a key transformation stage and also a reversible pathological process in various types of chronic liver ***,the pathogenesis of liver fibrosis still remains ***,we report that the calcium binding protein A11(S100A11)is consistently upregulated in the integrated data from GSE liver fibrosis and tree shrew liver proteomics.S100A11 is also experimentally activated in liver fibrosis in mouse,rat,tree shrew,and human with liver *** overexpression of S100A11 in vivo and in vitro exacerbates liver fibrosis,the inhibition of S100A11 improves liver ***,S100A11 activates hepatic stellate cells(HSCs)and the fibrogenesis process via the regulation of the deacetylation of Smad3 in the TGF-βsignaling pathway.S100A11 physically interacts with SIRT6,a deacetylase of Smad2/3,which may competitively inhibit the interaction between SIRT6 and Smad2/*** subsequent release and activation of Smad2/3 promote the activation of HSCs and ***,a significant elevation of S100A11 in serum is observed in clinical *** study uncovers S100A11 as a novel profibrogenic factor in liver fibrosis,which may represent both a potential biomarker and a promising therapy target for treating liver fibrosis and fibrosis-related liver diseases.

关键词： Chronic liver diseases Liver fibrosis S100A11 TGF-β SIRT6 Smad3

Galacto-oligosaccharides improve barrier function and relieve colonic inflammation via modulating mucosa-associated microbiota composition in lipopolysaccharides-challenged piglets

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Journal of animal Science and Biotechnology 2022年第1期13卷 240-255页

作者： Ren Gao Shiyi Tian Jing Wang Weiyun Zhu national center for international research on animal Gut Nutrition Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal HealthNational Experimental Teaching Demonstration Center of Animal ScienceLaboratory of Gastrointestinal MicrobiologyCollege of Animal Science and TechnologyNanjing Agricultural UniversityNanjing 210095China

Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal ***,the modulation of intestinal microbiota and intestinal function by GOS in intestinal inflammation injury models has rarely been *** this study,we investigated the effects of GOS on the colonic mucosal microbiota composition,barrier function and inflammatory response of lipopolysaccharides(LPS)-challenged suckling ***:A total of 18 newborn suckling piglets were divided into three groups,the CON group,the LPS-CON group and the LPS-GOS *** in the LPS-GOS group were orally fed with 1 g/kg body weight of GOS solution every *** the d 14,piglets in the LPS-CON and LPS-GOS group were challenged intraperitoneally with LPS *** piglets were slaughtered 2 h after intraperitoneal injection and ***:We found that the colonic mucosa of LPS-challenged piglets was significantly injured and shedding,while the colonic mucosa of the LPS-GOS group piglets maintained its ***,GOS significantly reduced the concentration of malondialdehyde(MDA)and the activity of reactive oxygen species(ROS)in the LPS-challenged suckling piglets,and significantly increased the activity of total antioxidant capacity(T-AOC).GOS significantly increased the relative abundance of norank_f_Muribaculaceae and Romboutsia,and significantly decreased the relative abundance of Alloprevotella,Campylobacter and Helicobacter in the colonic mucosa of LPS-challenged suckling *** addition,GOS increased the concentrations of acetate,butyrate and total short chain fatty acids(SCFAs)in the colonic digesta of LPS-challenged suckling *** significantly reduced the concentrations of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α)and cluster of differentiation 14(CD14),and the relative mRNA expression of Toll-like receptor 4(TLR4)and myeloid differentiatio

关键词： Barrier function Galacto-oligosaccharides Intestinal microbiota Lipopolysaccharides Suckling piglets

Lossof Adipose Growth Hormone Receptorin MiceEnhances Local Fatty Acid Trapping

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Lossof Adipose Growth Hormone Receptorin MiceEnhances Local ...

Strategies for generating mouse model resources of human disease

第三届中国生物物理学会代谢生物学分会学术研讨会

作者： Liyuan Ran Xiaoshuang Wang Ai Mi Yanshuang Liu Haoan Wang Dan Wang Yingjie Wu Institute for Genome engineered animal models of Human Diseases Dalian Medical University national center of genetically engineered animal models for international research Dalian Medical University Division of Endocrinology Diabetes and Bone DiseaseDepartment of MedicineIcahn Mount Sinai School of Medicine

＜正＞Growth hormone（GH） binds to its receptorGHR to exert its pleiotropic effects on growth and *** GH/GHR actions not only fail growth but also are involved in many metabolic disorders,as shown in murine models with global or tissue-specific GHR deficiency and clinical *** we constructed an adipose-specific GHR knockout mouse model Ad-GHRKO and studied the metabolic adaptability of the mice when stressed by high-fat

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Protein & Cell 2023年第12期14卷 866-870页

作者： Jirong Pan Ling Zhang Zhibing Huang Dalu Zhao He Li Yanan Fu Meng Wang Borui Chen Fuad A.Iraqi Grant Morahan Chuan Qin national Human Diseases animal Model Resource center NHC Key Laboratory of Human Disease Comparative MedicineBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious DiseasesBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal SciencesCAMS&PUMCNational Center of Technology Innovation for Animal ModelChangping National Laboratory(CPNL)Beijing 102206China Department of Clinical Microbiology and Immunology Sackler Faculty of MedicineTel-Aviv UniversityRamat AvivTel Aviv 69978Israel Harry Perkins Institute of Medical research QEII Medical Centre and Centre for Medical ResearchUniversity of Western AustraliaNedlandsPerthWA 6009Australia

The number of genetically modified mouse models that mimic human disease is growing rapidly,but only a tiny fraction has been commonly *** to The Knockout Mouse Program(Lloyd,2011),a public resource of mouse embryonic stem cells containing a null mutation in every gene in the mouse genome,8,916 mutant mice lines were phenotyped up to 19 July *** to the poor correlation between the genomic responses in the mouse models and those responses in human disease,and since humans differ significantly in their genetic vulnerability to common diseases,we still need better mouse models,especially for common and chronic human diseases,including cancer,pulmonary and cardiovascular diseases,obesity and diabetes,behavioral disorders,and neurodegenerative *** new models will be placed into a public repository,The China national Human Disease animal Model Resource center(NAMR).This project is funded by Ministry of Science and Technology of China and specializes in the creation,introduction,collection,preservation,and supply of animal model resources forhuman diseases.

关键词： diseases cardiovascular generating

Serine metabolism orchestrates macrophage polarization by regulating the IGF1–p38 axis

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Cellular & Molecular Immunology 2022年第11期19卷 1263-1278页

作者： Xiao Shan Penghui Hu Lina Ni Long Shen Yanan Zhang Zemin Ji Yan Cui Meihua Guo Haoan Wang Liyuan Ran Kun Yang Ting Wang Lei Wang Bin Chen Zhi Yao Vingjie Wu Qiujing Yu Tianjin Institute of Immunology Key Laboratory of Immune Microenvironment and Disease of the Ministry of EducationThe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical EpigeneticsTianjin Key Laboratory of Inflammation BiologyDepartment of ImmunologySchool of Basic Medical SciencesTianjin Medical University Division of Infectious Disease Second Hospital of Tianjin Medical UniversityTianjin300070China Institute for Genome engineered animal models of Human Diseases National Center of Genetically Engineered Animal Models for International ResearchDalian Medical UniversityDalian116044LiaoningChina Shandong Provincial Hospital School of Laboratory Animal and Shandong Laboratory Animal CenterScience and Technology Innovation CenterShandong First Medical University and Shandong Academy of Medical SciencesJinan250021ShandongChina The Province and Ministry Co-sponsored Collaborative Innovation center for Medical Epigenetics Department of Pharmacology and Tianjin Key Laboratory of Inflammation BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin300070China Tianjin Institute of Immunology Key Laboratory of Immune Microenvironment and Disease of the Ministry of EducationDepartment of ImmunologySchool of Basic Medical SciencesTianjin Medical UniversityTianjinChina Department of Molecular Pathobiology New York University College of DentistryNew YorkNY10010USA

Serine metabolism is reportedly involved in immune cell functions, but whether and how serine metabolism regulates macrophage polarization remain largely unknown. Here, we show that suppressing serine metabolism, either by inhibiting the activity of the key enzyme phosphoglycerate dehydrogenase in the serine biosynthesis pathway or by exogenous serine and glycine restriction, robustly enhances the polarization of interferon-γ-activated macrophages (M(IFN-γ)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo. Mechanistically, serine metabolism deficiency increases the expression of IGF1 by reducing the promoter abundance of S-adenosyl methionine-dependent histone H3 lysine 27 trimethylation. IGF1 then activates the p38-dependent JAK–STAT1 axis to promote M(IFN-γ) polarization and suppress STAT6-mediated M(IL-4) activation. This study reveals a new mechanism by which serine metabolism orchestrates macrophage polarization and suggests the manipulation of serine metabolism as a therapeutic strategy for macrophage-mediated immune diseases.

关键词： Serine metabolism PHGDH Macrophage polarization SAM IGF1 p38

Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

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animal models and Experimental Medicine 2023年第2期6卷 146-154页

作者： Yuhang Sun Bowen Guan Xing Liu Lingyan Zhang Xinpei Wang Aimin Meng Ran Gao national Human Diseases animal Model Resource center NHC Key Laboratory of Human Disease Comparative MedicineBeijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PUMC)National Center of Technology Innovation for Animal ModelBeijingChina

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor *** susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of *** susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary ***:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in *** urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed *** for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase *** on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU ***:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC *** GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

关键词： angiotensin I converting enzyme busulfan hematopoietic stem cell injury inbred genetic diversity mice urinary marker

Distinct neuronal excitability alterations of medial prefrontal cortex in early-life neglect model of rats

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animal models and Experimental Medicine 2022年第3期5卷 274-280页

作者： Yu Zhang Xiuping Sun Changsong Dou Xianglei Li Ling Zhang Chuan Qin NHC Key Laboratory of Human Disease Comparative Medicine Institute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)Comparative Medicine CenterPeking Union Medical College(PUMC)BeijingChina national Human Diseases animal Model Resource center BeijingChina Beijing Engineering research center for Experimental animal models of Human Critical Diseases BeijingChina international center for Technology and Innovation of animal model BeijingChina Changping national laboratory(CPNL) BeijingChina

Object:Early-life neglect has irreversible emotional effects on the central nervous *** this work,we aimed to elucidate distinct functional neural changes in me-dial prefrontal cortex(mPFC)of model ***:Maternal separation with early weaning was used as a rat model of early-life *** excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch ***:Glutamatergic and GABAergic neurons of mPFC were distinguished by typi-cal electrophysiological *** excitation of mPFC glutamatergic neurons was significantly increased in male groups,while the excitation of mPFC GABAergic neurons was significant in both female and male groups,but mainly in terms of rest membrane potential and amplitude,***:Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect,which can contribute to distinct mechanisms for emotional and cognitive manifestations.

关键词： early-life neglect model GABAergic glutamatergic maternal separation with early weaning medial prefrontal cortex neuronal excitability

Novel method for the recognition of Jinnan cattle action using bottleneck attention enhanced two-stream neural network

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international Journal of Agricultural and Biological Engineering 2024年第3期17卷 203-210页

作者： Wangli Hao Meng Han Kai Zhang Li Zhang Wangbao Hao Fuzhong Li Zhenyu Liu School of Software Shanxi Agricultural UniversityJinzhong 030801ShanxiChina Yuncheng national Jinnan Cattle Genetic Resources and Gene Protection center Yongji 044500ShanxiChina Yongji Puzhou Old City Beimenwai Cattle Farm Yongji 044500ShanxiChina College of Engineering Shanxi Agricultural UniversityJinzhong 030801ShanxiChina

Effective and accurate action recognition is essential to the intelligent breeding of the Jinnan ***,there are still several challenges in the current Jinnan cattle action *** methods are based on manual characteristics and low recognition *** study is aimed at the efficient and accurate development of Jinnan cattle action recognition methods to overcome existing problems and support intelligent *** acquired data from the previous methods contain a lot of noise,which will cause individual cattle to have excessive behaviors due to *** the high labor costs,low efficiency,and low model accuracy of the above approaches,this study developed a bottleneck attention-enhanced two-stream(BATS)Jinnan cattle action recognition *** primarily comprises a Spatial Stream Subnetwork,a Temporal Stream Subnetwork,and a Bottleneck Attention *** can capture the spatial-channel dependencies in RGB and optical flow two branches respectively,so as to extract richer and more robust ***,the decision of the two branches can be fused to gain improved cattle action recognition *** with the traditional methods,the model proposed in this study has achieved state-of-the-art recognition performance,and the accuracy of motion recognition was 96.53%,which was 4.60%higher than other *** method significantly improves the efficiency and accuracy of behavior recognition and provides an important research foundation and direction for the development of higher-level behavior analysis models in the future development of smart animal husbandry.

关键词： Jinnan cattle action recognition bottleneck attention two-stream neural network

Designed fabrication of active tumor targeting covalent organic framework nanotherapeutics via a simple post-synthetic strategy

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Nano research 2023年第5期16卷 7085-7094页

作者： Yue Yu Guoxin Zhang Zhongping Li Jia Wang Yang Liu Rahul Bhardwaj Renu Wadhwa Yuki Nagao Mototada Shichiri Ran Gao Biomedical research Institute National Institute of Advanced Industrial Science and Technology(AIST)Osaka 563-8577Japan AIST-INDIA DAILAB DBT-AIST International Center for Translational&Environmental Research(DAICENTER)AISTTsukubaIbaraki 305-8565Japan Beijing Engineering research center for Experimental animal models of Human Critical Diseases NHC Key Laboratory of Human Disease Comparative MedicineNational Human Diseases Animal Model Resource CenterInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollageBeijing 100021China School of Materials Science Japan Advanced Institute of Science and TechnologyIshikawa 923-1211Japan Department of Chemical and Biomolecular Engineering Yonsei University50 Yonsei-roSeodaemun-guSeoul 120-749Republic of Korea Flexible 3D System Integration Laboratory SANKENOsaka UniversityOsaka 567-0047Japan

Developing agents that can accurately differentiate tumors from normal healthy tissues is of utmost importance for safe cancer *** targeting has been considered as an effective technique for tumor *** this work,we demonstrate a folate-functionalized nanoscale covalent organic framework(FATD nCOF)highly specific to cancer cells through active targeting of their enriched folate receptors(FRs).The FATD nCOF prepared by simple post-synthetic modification of the COF surface defeats disperses well in water and exhibits a high loading capacity for various anticancer *** biocompatible FATD nCOF is selectively internalized by FR-harboring cancer cells and consequently augments the efficacy of the loaded drug,Withaferin A(Wi-A),for targeted cancer cell *** biomolecular mechanism studies,Wi-A-loaded FATD(FATD@Wi-A)nanocomposites show remarkably a higher rate of apoptosis in FR-enriched cancer *** analyses of FR-positive and FR-negative tumor xenografts reveal enhanced selective antitumor activity of FATD@Wi-A *** together,the study findings suggest that FATD nCOF holds great promise for active targeting of tumors in *** simple yet effective technology might be valuable for creating new state-of-the-art COFs for chemical and biomedical applications.

关键词： covalent organic framework active targeting folate receptor drug delivery cancer therapy