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Strategies for Dissecting the Genetic Driving of Conserved Noncoding-Elements for Evolutionary Development of the Corpus Callosum

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Neuroscience Bulletin 2024年第7期40卷 1025-1027页

作者： Yaxin Ye Boxing Jin Hao W.Zhang Nengyin Sheng State key laboratory of Genetic Resources and Evolution Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan ProvinceKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China Kunming College of Life Science University of Chinese Academy of SciencesKunming 650201China Center for Excellence in animal Evolution and Genetics Chinese Academy of SciencesKunming 650201China

With the efforts in developmental biology and neuroscience during the past several decades,our knowledge has been significantly advanced about the genetic,cellular,and molecular mechanisms underlying brain development and ***,we should keep in mind that the human brain is the product of complex evolutionary processes,and there is a trade-off between brain evolution and neurological disorders[1].

关键词： function. neurological knowledge

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

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

SARS-CoV-2 breakthrough infections following inactivated vaccine vaccination induce few neutralizing antibodies against the currently emerging Omicron XBB variants

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Virologica Sinica 2024年第1期39卷 173-176页

作者： Fan Shen Chun Liang Cui-Xian Yang Ying Lu An-Qi Li Ying Duan Mi Zhang c Ren-Rong Tian a Xing-Qi Dong Yong-Tang Zheng Wei Pang key laboratory of Bioactive Peptides of yunnan province/key laboratory of animal models and human disease mechanisms of the chinese academy of sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming650223China University of chinese academy of sciences Beijing100049China yunnan Provincial Infectious disease Hospital Kunming650399China Department of Pathogen Biology and Immunology Faculty of Basic Medical ScienceKunming Medical UniversityKunming650500China

Dear Editor,COVID-19 inactivated vaccines have been extensively administered ***,the majority of the chinese population has experiencedbreakthrough infections from SARS-CoV-2 ancestral,Delta or Omicronvariants over the past three years,particularly during the wave of Omicron BA.5 and BA.7 variants at the end of 2022(Zhu et al.,2023).Subsequently,new Omicron variants,such as BQ.1,BQ.1.1,XBB,XBB.1/XBB.1.9,and XBB.1.5/XBB.1.9.1,are emerging in China(Yueetal.,2023;Zhu et al.,2023).Therefore,it is an urgentneed and a publichealth imperative to assess the extent of the immunoprotection established in this population.

关键词： breakthrough neutral Omi

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 Zoologythe Chinese Academy of SciencesKunmingYunnan ProvinceChina Tsinghua-Peking Center for Life sciences BeijingChina National Institute on Drug Dependence Peking UniversityBeijingChina PKU/McGovern Institute for Brain Research Peking UniversityBeijingChina Institute of Mental Health National Clinical Research Center for Mental DisordersKey Laboratory of Mental Health and Peking University Sixth HospitalPeking UniversityBeijingChina

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 ***,the underlying mechanisms of lncRNAs during neurodegeneration remain poorly *** 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 ***,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

Semisynthesis of homogeneous spike RBD glycoforms from SARS-CoV-2 for profiling the correlations between glycan composition and function

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National Science Review 2024年第2期11卷 145-154页

作者： Farong Ye Cheng Li Feng-Liang Liu Xinliang Liu Peng Xu Rong-Hua Luo Wenping Song Yong-Tang Zheng Tianlei Ying Biao Yu Ping Wang Center for Chemical Glycobiology Frontiers Science Center for Transformative Molecules Zhangjiang Institute for Advanced Study School of Chemistry and Chemical Engineering Shanghai Jiao Tong University MOE/NHC/CAMS key laboratory of Medical Molecular Virology Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection Shanghai Institute of Infectious Disease and BiosecurityShanghai Engineering Research Center for Synthetic ImmunologySchool of Basic Medical Sciences Shanghai Medical College Fudan University key laboratory of animal models and human disease mechanisms of chinese academy of sciences/key laboratory of Bioactive Peptides of yunnan province Center for Biosafety Mega-Science Kunming Institute of ZoologyChinese Academy of Sciences State key laboratory of Bioorganic and Natural Products Chemistry Center for Excellence in Molecular Synthesis Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shenzhen Research Institute of Shanghai Jiao Tong University

Vaccines have been the primary remedy in the global fight against coronavirus disease 2019（COVID-19）.The receptor-binding domain（RBD） of the spike protein, a critical viral immunogen, is affected by the heterogeneity of its glycan structures and relatively low immunogenicity. Here, we describe a scalable synthetic platform that enables the precise synthesis of homogeneously glycosylated RBD, facilitating the elucidation of carbohydrate structure–function relationships. Five homogeneously glycosylated RBDs bearing biantennary glycans were prepared, three of which were conjugated to T-helper epitope(Tpep) from tetanus toxoid to improve their weak immune response. Relative to natural HEK293-derived RBD, synthetic RBDs with biantennary N-glycan elicited a higher level of neutralising antibodies against SARS-CoV-2 in mice. Furthermore, RBDs containing Tpepelicited significant immune responses in transgenic mice expressing human angiotensin-converting enzyme 2. Our collective data suggest that trimming the N-glycans and Tpepconjugation of RBD could potentially serve as an effective strategy for developing subunit vaccines providing efficient protection.

关键词： peptide ligation glycosylation glycoprotein

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science China(Life sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao Lin-Lin Liu Jian Sun Lian Jin Hai-Bing Xie Jian-Bo Li Hui Xu Dong-Dong Wu Xiao-Lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-Jie Sun Liang-Hu Qu Jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping Zhang State key laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China key laboratory of animal models and human disease mechanisms of the chinese academy of sciences and yunnan province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State key laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The key laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai key laboratory of Cell Engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

human-specific insertions play important roles in human phenotypes and *** we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome ***,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee *** have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in *** addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in *** of Insert-446 prevented cell proliferation and migration in cancer and normal *** results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B *** findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

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Zoological Research 2024年第4期45卷 747-766页

作者： Hong-Yi Zheng Tian-Zhang Song Yong-Tang Zheng State key laboratory of Genetic Evolution&animal models KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China National Resource Center for Non-human Primates National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole ***,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 *** among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of *** effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and *** animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

关键词： SARS-CoV-2 COVID-19 animal models Infection immunology Immunotherapy

Anemoside B4 inhibits SARS-CoV-2 replication in vitro and in vivo

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chinese Herbal Medicines 2024年第1期16卷 106-112页

作者： Mingyue Xiao Ronghua Luo Qinghua Liang Honglv Jiang Yanli Liu Guoqiang Xu Hongwei Gao Yongtang Zheng Qiongming Xu Shilin Yang College of Pharmaceutical sciences Soochow UniversitySuzhou 215123China key laboratory of animal models and human disease mechanisms of chinese academy of sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Jiangsu key laboratory of Neuropsychiatric diseases and Jiangsu key laboratory of Preventive and Translational Medicine for Geriatric diseases Soochow UniversitySuzhou 215123China College of Pharmacy Guangxi University of Chinese MedicineNanning 530000China

Objective: Anemoside B4(AB4), the most abundant triterpenoidal saponin isolated from Pulsatilla chinensis, inhibited influenza virus FM1 or Klebsiella pneumoniae-induced pneumonia. However, the anti-SARS-CoV-2 effect of AB4 has not been unraveled. Therefore, this study aimed to determine the antiviral activity and potential mechanism of AB4 in inhibiting human coronavirus SARS-CoV-2 in vivo and in ***: The cytotoxicity of AB4 was evaluated using the Cell Counting Kit-8(CCK8) assay. SARS-CoV-2 infected HEK293T, HPAEpiC, and Vero E6 cells were used for in vitro assays. The antiviral effect of AB4 in vivo was evaluated by SARS-CoV-2-infected hACE2-IRES-luc transgenic mouse model. Furthermore,label-free quantitative proteomics and bioinformatic analysis were performed to explore the potential antiviral mechanism of action of AB4. Type Ⅰ IFN signaling-associated proteins were assessed using Western blotting or immumohistochemical ***: The data showed that AB4 reduced the propagation of SARS-CoV-2 along with the decreased Nucleocapsid protein(N), Spike protein(S), and 3C-like protease(3CLpro) in HEK293T cells. In vivo antiviral activity data revealed that AB4 inhibited viral replication and relieved pneumonia in a SARS-CoV-2 infected mouse model. We further disclosed that the antiviral activity of AB4 was associated with the enhanced interferon(IFN)-β response via the activation of retinoic acid-inducible gene Ⅰ(RIG-1) like receptor(RLP) pathways. Additionally, label-free quantitative proteomic analyses discovered that 17 proteins were significantly altered by AB4 in the SARS-CoV-2 coronavirus infections cells. These proteins mainly clustered in RNA ***: Our results indicated that AB4 inhibited SARS-CoV-2 replication through the RLR pathways and moderated the RNA metabolism, suggesting that it would be a potential lead compound for the development of anti-SARS-CoV-2 drugs.

关键词： anemoside B4 interferon RNA metabolism quantitative proteomics SARS-CoV-2