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Dietary copper requirement of broilers fed a corn-soybean meal diet during 22—42 d of age

animal Nutrition 2024年第1期16卷 96-104页

作者： Ling Zhu Wei Wu Bingxin Wu Yun Hu Liyang Zhang Weiyun Zhang Tingting Li Xiaoyan Cui Feiyu Gao Ding Li Xugang Luo Shengchen Wang Poultry Mineral Nutrition laboratory College of Animal Science and TechnologyYangzhou UniversityYangzhou 225000China Mineral Nutrition Research Division State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China

This research was to assess the dietary copper(Cu)requirement of broiler chickens fed a practical cornsoybean meal diet during 22—42 d of age.A total of 288 numbered Arbor Acres male broilers at 22 d of age were randomly allotted 6 treatments with 8 replicate cages(6 broilers per cage)per *** were fed a Cu-unsupplemented corn-soybean meal basal diet(control,containing 7.36 mg Cu/kg)or the basal diet added with 3,6,9,12,or 15 mg Cu/kg from CuSO_(4)·5H_(2)O for 21 ***,asymptotic and broken-line models were fitted and the best fitted models were selected to determine dietary Cu *** results revealed that the contents of Cu in serum and liver,m RNA expression levels of Cu-and zinc-containing superoxide dismutase(CuZnSOD)in liver and monoamine oxidase b(MAO B)in heart,as well as protein expression level of CuZnSOD in liver were affected(Pmodels(P<0.05)of the above indexes were 10.45—13.81 mg/*** was concluded that mRNA expression levels of CuZnSOD in liver and MAO B in heart,as well as liver CuZnSOD protein expression level were new specific sensitive biomarkers for estimating dietary Cu requirements,and the dietary Cu requirement was recommended to be 14 mg/kg to support Cu metabolic needs related to key Cucontaining enzymes in broilers fed the corn-soybean meal diet during 22—42 d of age,which was higher than the dietary Cu requirement(8 mg/kg)for broilers at the corresponding stage suggested by the Chinese Feeding Standard of Chicken.

关键词： Copper Copper content Gene expression of copper-containing enzyme Requirement Broiler

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Synthesis and anti-HIV activities of phorbol derivatives

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Chinese Journal of Natural Medicines 2024年第2期22卷 146-160页

作者： HUANG Xiaolei TANG Chengrun HUANG Xusheng YANG Yun LI Qirun MA Mengdi ZHAO Lei YANG Liumeng CUI Yadong ZHANG Zhenqing ZHENG Yongtang ZHANG Jian College of Pharmaceutical Science Soochow UniversitySuzhou 215123China Key laboratory of animal models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China

In this study,37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated,building upon our previous synthesis of 51 phorbol derivatives.12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out,demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia *** derivatives exhibited a higher safety index compared with the positive control *** them,12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol,designated as compound 3c,exhibited the most potent anti-HIV-1 activity(EC_(50)2.9 nmol·L^(−1),CC50/EC_(50)11117.24)and significantly inhibited the formation of syncytium(EC_(50)7.0 nmol·L^(−1),CC50/EC_(50)4891.43).Moreover,compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase *** titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C(PKC).Therefore,compound 3c emerges as a potential candidate for developing new anti-HIV drugs.

关键词： Phorbol esters Anti-HIV-1 activity Syncytia formation 12-(Trans-4-fluorocinnamoyl)-13-decanoyl phorbol Safety index HIV-1 entry inhibitor HIV-1 reverse transcriptase inhibitor PKC activator

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Genetically modified pigs:Emerging animal models for hereditary hearing loss

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Zoological Research 2024年第2期45卷 284-291页

作者： Xiao Wang Tian-Xia Liu Ying Zhang Liang-Wei Xu Shuo-Long Yuan A-Long Cui Wei-Wei Guo Yan-Fang Wang Shi-Ming Yang Jian-Guo Zhao State Key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Department of Otolaryngology-Head and Neck Surgery Institute of OtolaryngologyChinese PLA General HospitalBeijing 100853China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230022China State Key laboratory of animal Biotech Breeding Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing100193China

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for *** investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are *** have been extensively used as valuable large animal models in biomedical *** this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing ***,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL ***,this review provides insights and perspectives for future studies on HHL using porcine models.

关键词： Pigs animal models Hereditary hearing loss Genetic modification Inner ear

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《动物模型与实验医学(英文)》(animal models and Experimental Medicine,AMEM)审稿人招募

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中国实验动物学报 2024年第6期32卷 732-732页

作者： animal models and Experimental Medicine编辑部 animal models and Experimental Medicine编辑部

《动物模型与实验医学(英文)》(animal models and Experimental Medicine,AMEM)是国际化的,开放获取的英文期刊,致力于为实验动物物种资源、实验动物模型、实验动物技术、实验动物福利及实验医学、比较医学和转化医学等科学研究搭建国... 详细信息

《动物模型与实验医学(英文)》(animal models and Experimental Medicine,AMEM)是国际化的,开放获取的英文期刊,致力于为实验动物物种资源、实验动物模型、实验动物技术、实验动物福利及实验医学、比较医学和转化医学等科学研究搭建国际交流平台,发挥学科引领和学术创新导向作用。自创刊以来,相继被CSCD(核心)、DOAJ、PubMed、WJCI、MEDLINE、ESCI、Scopus等国内外数据库收录,连续3年入选“中国国际影响力优秀学术期刊”。影响因子3􀆰8,且CiteScore值从2022年初的5.5上升到6􀆰3,期刊影响力得到国际认可,成为实验动物科学领域国际同行创新性研究成果的重要展示平台,更是实验动物科研工作者国际学术交流的重要渠道。AMEM与国际著名出版集团Wiley合作出版,稳步推进期刊的国际化,并重视编委、作者、审稿人队伍的国际化。为提供更广阔的学术交流平台和成长空间,同时增强AMEM在实验动物科学领域的学科引领作用,AMEM诚挚邀请海内外对动物模型研究和实验医学方面有浓厚兴趣、有高度热忱、有专业素养、有独到洞察的专家学者成为审稿人。

关键词：开放获取实验医学展示平台实验动物科学审稿人比较医学国际认可 Scopus

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Identification of novel genes associated with atherosclerosis in Bama miniature pig

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animal models and Experimental Medicine 2024年第3期7卷 377-387页

作者： Dengfeng Ding Yuqiong Zhao Yunxiao Jia Miaomiao Niu Xuezhuang Li Xinou Zheng Hua Chen laboratory animal Center Chinese PLA General HospitalBeijingChina

Background:Atherosclerosis is a chronic cardiovascular disease of great ***,it is difficult to establish a direct connection between conventional small animal models and clinical *** pig's genome,physiology,and anatomy reflect human biology better than other laboratory animals,which is crucial for studying the pathogenesis of ***:We used whole-genome sequencing data from nine Bama minipigs to perform a genome-wide linkage analysis,and further used bioinformatic tools to filter and identify underlying candidate *** gene function prediction was performed using the online prediction tool STRING *** and immunofluorescence were used to detect the expression of proteins encoded by candidate ***:We mapped differential single nucleotide polymorphisms(SNPs)to genes and obtained a total of 102 differential genes,then we used GO and KEGG pathway enrichment analysis to identify four candidate genes,including SLA-1,SLA-2,SLA-3,and *** cause changes in the primary and tertiary structures of SLA-I and TAP2 proteins,the primary structures of these two proteins have undergone amino acid changes,and the tertiary structures also show slight *** addition,immunohistochemistry and immunofluorescence results showed that the expression changes of TAP2 protein in coronary arteries showed a trend of increasing from the middle layer to the inner ***:We have identified SLA-I and TAP2 as potential susceptibility genes of atherosclerosis,highlighting the importance of antigen processing and immune response in atherogenesis.

关键词： atherosclerosis candidate genes genome-wide linkage analysis major histocompatibility complex whole genome sequencing

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Seco-cyclic phorbol derivatives and their anti-HIV-1 activities

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Chinese Journal of Natural Medicines 2024年第4期22卷 365-374页

作者： HUANG Xiaolei HUANG Xusheng LI Qirun MA Mengdi CUI Yadong YANG Liumeng WANG Haibo LUO Ronghua CHEN Jinglei YANG Jingxuan LIN Jinrong LI Duxin ZHENG Yongtang ZHANG Jian College of Pharmaceutical Science Soochow UniversitySuzhou 215123China Key laboratory of animal models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming 650204China College of Traditional Chinese Medicine Yunnan University of Chinese MedicineKunming 650500China

Phorbol esters are recognized for their dual role as anti-HIV-1 agents and as activators of protein kinase C(PKC).The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20,C3/C4,and C9 of ***,the lipids located at positions C12/C13 are essential for both the anti-HIV-1 activity and the formation of the PKC-ligand *** influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti-HIV-1 activity requires further *** research entailed the hydrolysis of phorbol,producing seco-cyclic phorbol *** anti-HIV-1 efficacy of these derivatives was assessed,and the affinity constant(Kd)for PKC-δprotein of selected seco-cyclic phorbol derivatives was determined through isothermal titration *** findings suggest that the chemical modification of cyclopropanols could affect both the anti-HIV-1 activity and the PKC binding ***,compound S11,with an EC_(50) of 0.27μmol·L^(−1) and a CC_(50) of 153.92μmol·L^(−1),demonstrated a potent inhibitory effect on the intermediate products of HIV-1 reverse transcription(ssDNA and 2LTR),likely acting at the viral entry stage,yet showed no affinity for the PKC-δ*** results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti-HIV-1 activity.

关键词： seco-Cyclic phorbol derivatives Hydrolysis reaction Cyclopropane ring Esterification Anti-HIV-1 agent

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Long non-coding RNAs with essential roles in neurodegenerative disorders

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Neural Regeneration Research 2024年第6期19卷 1212-1220页

作者： Wandi Xiong Lin Lu Jiali Li Key laboratory of animal models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology the Chinese Academy of Sciences Tsinghua-Peking Center for Life Sciences National Institute on Drug Dependence Peking University PKU/McGovern Institute for Brain Research Peking University Institute of Mental Health National Clinical Research Center for Mental Disorders Key Laboratory of Mental Health and Peking University Sixth Hospital Peking University

Recently, with the advent of high-resolution and high-throughput sequencing technologies, an increasing number of long non-coding RNAs(lncRNAs) have been found to be involved in the regulation of neuronal function in the central nervous system with specific spatiotemporal patterns, across different neurodegenerative diseases. However, the underlying mechanisms of lncRNAs during neurodegeneration remain poorly understood. This review provides an overview of the current knowledge of the biology of lncRNAs and focuses on introducing the latest identified roles, regulatory mechanisms, and research status of lncRNAs in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Finally, this review discusses the potential values of lncRNAs as diagnostic biomarkers and therapeutic targets for neurodegenerative diseases, hoping to provide broader implications for developing effective treatments.

关键词： Alzheimer's disease amyotrophic lateral sclerosis biomarker Huntington's disease long non-coding RNAs neurodegenerative diseases Parkinson's disease therapy transcriptional regulation translational regulation

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In vivo evaluation of guide-free Cas9-induced safety risks in a pig model

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SIGNAL TRANSDUCTION AND TARGETED THERAPY 2024年第1期9卷 1-14页

作者： Ge, Weikai Gou, Shixue Zhao, Xiaozhu Jin, Qin Zhuang, Zhenpeng Zhao, Yu Liang, Yanhui Ouyang, Zhen Liu, Xiaoyi Chen, Fangbing Shi, Hui Yan, Haizhao Wu, Han Lai, Liangxue Wang, Kepin Guangzhou Med Univ Chinese Acad Sci Guangzhou Inst Biomed & Hlth Joint Sch Life SciChina New Zealand Joint Lab Bio Guangzhou 510530 Peoples R China Hainan Prov Res Ctr Sanya Inst Swine Resource Lab Anim Sanya 572000 Peoples R China Wuyi Univ Guangdong Prov Key Lab Large Anim Models Biomed Jiangmen 529020 Peoples R China Guangzhou Natl Lab Guangzhou 510005 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China Chinese Acad Med Sci Res Unit Generat Large Anim Dis Models 2019RU015 Guangzhou 510530 Peoples R China

The CRISPR/Cas9 system has shown great potential for treating human genetic diseases through gene therapy. However, there are concerns about the safety of this system, specifically related to the use of guide-free Cas9. Previous studies have shown that guide-free Cas9 can induce genomic instability in vitro. However, the in vivo safety risks associated with guide-free Cas9 have not been evaluated, which is necessary for the development of gene therapy in clinical settings. In this study, we used doxycycline-inducible Cas9-expressing pigs to evaluate the safety risks of guide-free Cas9 in vivo. Our findings demonstrated that expression of guide-free Cas9 could induce genomic damages and transcriptome changes in vivo. The severity of the genomic damages and transcriptome changes were correlate with the expression levels of Cas9 protein. Moreover, prolonged expression of Cas9 in pigs led to abnormal phenotypes, including a significant decrease in body weight, which may be attributable to genomic damage-induced nutritional absorption and metabolic dysfunction. Furthermore, we observed an increase in whole-genome and tumor driver gene mutations in pigs with long-term Cas9 expression, raising the risk of tumor occurrence. Our in vivo evaluation of guide-free Cas9 in pigs highlights the necessity of considering and monitoring the detrimental effects of Cas9 alone as genome editing via the CRISPR/Cas9 system is implemented in clinical gene therapy. This research emphasizes the importance of further study and implementation of safety measures to ensure the successful and safe application of the CRISPR/Cas9 system in clinical practice.

关键词： DNA-DAMAGE GENOME CRISPR-CAS9 ALIGNMENT

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Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury

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Virologica Sinica 2024年第2期39卷 309-318页

作者： Jian-Bo Cao Shu-Tong Zhu Xiao-Shan Huang Xing-Yuan Wang Meng-Li Wu Xin Li Feng-Liang Liu Ling Chen Yong-Tang Zheng Jian-Hua Wang Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China School of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230026China Key laboratory of Bioactive Peptides of Yunnan Province Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of SciencesKIZCUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China University of Chinese Academy of Sciences Beijing 101408China

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of *** research,along with others',has demonstrated that mast cells(MCs)play a vital role in the initiation of hyper-inflammation caused by *** previous study,we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized ***,we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells,leading to subsequent lung *** trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation,and inflammation in these regions could promote viral *** are widely distributed throughout the respiratory ***,in this study,we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial *** analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with *** degranulation caused lesions in trachea,and the formation of papillary hyperplasia was *** transcriptome analysis in bronchial epithelial cells,we found that MC degranulation significantly altered multiple cellular signaling,particularly,leading to upregulated immune responses and *** administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in *** together,our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue ***,our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation,thereby preventing tissue damage caused by hyper-inflammation.

关键词： SARS-CoV-2 Mast cell(MC) Bronchial epithelial cell Inflammation Tracheal injury

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Zika virus infection induces glycometabolic disorder in northern pig-tailed macaques

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Science China Life Sciences 2024年

作者： Qing Li Ren-Hua Yang Yan Hu Bei-Bei Tang Ying-Jie Jiang Chang-Bo Zheng Tian-Zhang Song State Key laboratory of Genetic Evolution&animal models Key Laboratory of Bioactive Peptides of Yunnan ProvinceKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences School of Pharmaceutical Science&Yunnan Key laboratory of Pharmacology for Natural Products Kunming Medical University University of Chinese Academy of Sciences KIZ-SU Joint laboratory of animal Model and Drug Development College of Pharmaceutical SciencesSoochow University

Dear Editor,The Zika virus (ZIKV) was first identified in Africa in 1947 but remained relatively obscure for nearly 70 ***,from 2014 to 2016,ZIKV was introduced into Brazil from the Pacific Islands,leading to its rapid dissemination throughout the Americas (Fauci and Morens,2016).This mosquito-borne virus is distinguished by its capacity to cause congenital defects,as evidenced by the microcephaly epidemic in Brazil,and has been declared a Public Health Emergency of International Concern (Gulland,2016).

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