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Altered 3D genome reorganization mediates precocious myeloid differentiation of aged hematopoietic stem cells in inflammation

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Science China Life Sciences 2025年

作者： Xinyu Cui Yu Dong Qiang Zhan Yixin Huang Qianshu Zhu Zihao Zhang Guang Yang Liping Wang Shijun Shen Jia Zhao Zhiyi Lin Jiatong Sun Zhongqu Su Yihan Xiao Chuyu Zhang Yuwei Liang Lu Shen Lichen Ji Xuguang Zhang Jiqing Yin Hong Wang Zhiyang Chen Zhenyu Ju Cizhong Jiang Rongrong Le Shaorong Gao Clinical and Translational Research Center of Shanghai First Maternity & Infant Hospital Frontier Science Center for Stem Cells School of Life Sciences and Technology Tongji University key laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji Hospital School of Life Sciences and Technology Tongji University key laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University shandong key laboratory of animal bioengineering and disease prevention College of Animal Science and Technology Shandong Agricultural University Department of Joint Surgery Shanghai East Hospital Tongji University School of Medicine Shanghai Institute of Nutrition and Health Chinese Academy of Sciences

Inflammation is a driving force of hematopoietic stem cells(HSCs) aging, causing irreversible exhaustion of functional HSCs. However, the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understood. Here, we find that transient LPS exposure primes aged HSCs to undergo accelerated differentiation at the expense of self-renewal, leading to depletion of HSCs. Meanwhile, the central regulator nuclear factor kappa B(NF-κB) mediating functional impairment by inflammation insult induces differential transcriptional response in aged HSCs compared with young HSCs, with precocious activation of myeloid lineage genes. Altered compartmentalization and chromatin loop formation are associated with aging-related differential transcriptional response in HSCs upon lipopolysaccharide(LPS)stimulation. Mechanistically, enhancer and promoter regions of myeloid lineage genes in aged HSCs are more accessible and display more rapid and prominent CTCF occupancy upon LPS stimulation. Our study provides comprehensive resources for the three-dimensional(3D)genome structure of HSCs and sheds light into the ordered genome organization and the associated transcriptome signature underlying HSCs aging.

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Lung-targeted polyzwitterionic lipid nanoparticles for effective treatment of lung inflammation

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Science China Chemistry 2025年

作者： Wen Zhang Jiaxin Li Nan Wang Muzi Li Chen Peng Xinyue Zhang Guanghui Ouyang Yan Li Beijing key laboratory for bioengineering and Sensing Technology School of Chemistry and Biological Engineering University of Science and Technology Beijing CAS key laboratory of Colloid Interface and Chemical Thermodynamics Institute of Chemistry Chinese Academy of Sciences

Lipid nanoparticles (LNPs) are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease treatment. Although LNPs are particularly advantageous for in vivo delivery, the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly challenging. To address this issue, we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine)(PMPC) modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA (siRNA). Three libraries with 90PMPC-LNPs@siRNA were established. The polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about90%. The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin, mediating lung-targeted delivery of siRNA. With good cellular uptake and endo/lysosomal escape ability, in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α (TNF-α) could significantly down-regulate the TNF-α in mRNA and protein levels, and improved the pathological features of lung inflammation. Polyzwitterionic PMPC-LNPs@siRNA achieved safe and efficient treatment of lung inflammation. Therefore, this work offered a promising siRNA therapeutic approach for lung diseases.

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Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis

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Science China Life Sciences 2025年第1期 103-115页

作者： Xizi Luo Nan Zhang Yuntao Liu Beibei Du Xuan Wang Tianxu Zhao Bingqiang Liu Shishun Zhao Jiazhang Qiu Guoqing Wang State key laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Basic MedicineJilin University State key laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Veterinary MedicineJilin University College of Mathematics Jilin University Bioinformatic Lab School of MathematicsShandong University Department of Cardiology China-Japan Union HospitalJilin University

The coronavirus disease 2019（COVID-19） outbreak caused by the severe acute respiratory syndrome coronavirus-2（SARS-CoV-2） developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors,patients who died during the hypercoagulable period of characteristic coagulation abnormality（CAC）, and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

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Identification of an H1N1 subtype of swine influenza virus and serological analysis

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Journal of Integrative Agriculture 2019年第7期18卷 1436-1442页

作者： SUN Fa-chao TAN Min ZHANG Yuan-chao WANG Yu-chao CAO Sheng-liang DING Guo-fei CONG Fang-yuan GUO Li-hong LIU Si-dang XIAO Yi-hong Department of Basic Veterinary Medicine College of Animal Science and Veterinary Medicine/Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention/Shandong Provincial Engineering Technology Research Center of Animal Disease Control and PreventionShandong Agricultural University

To investigate the epizootic of swine influenza virus(SIV),60 nasal swabs were collected from a clinical cases of pig farm in Tai’an City,shandong Province of China in April *** was isolated by inoculating into 10-day-old Special Pathogen Free embryonated eggs and the whole genome was *** H1N1 subtype SIV was isolated and designated as A/swine/shandong/TA04/2017(H1N1).Phylogenetic analysis showed that apart from the polymerase A(PA) fragment belonging to the 2009 pandemic H1N1 branch,seven genome segments belonged to avian-like H1N1 influenza virus *** cleavage site sequence of the hemagglutinin(HA) protein was PSIQSR↓G,which is a typical molecular biological *** potential N-glycosylation sites(N14,N26,N277,N484 and N543) were found in the HA *** further investigate the epidemiology of SIV in this farm,the 995 serum samples were assessed with EAH1N1 2009 pandemic H1N1 and H3 N2 *** results showed that the total positive rate was 65.43%.The positive rates of single virus infection detected by EAH1N1,2009 pdmH1N1 and H3 N2 for serum HI(Hemagglutination inhibition) were 48.35,30.85 and 7.47%,*** results showed that SIV in shandong Province has been reassorted in some segments and the SIV-positive rate was high on the SIV outbreak *** data provide evidence of an epizootic of SIV.

关键词： SIV H1N1 subtype genetic analysis molecular feature serology

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Breed identification using breed‑informative SNPs and machine learning based on whole genome sequence data and SNP chip data

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Journal of animal Science and Biotechnology 2023年第5期14卷 1941-1953页

作者： Changheng Zhao Dan Wang Jun Teng Cheng Yang Xinyi Zhang Xianming Wei Qin Zhang shandong Provincial key laboratory of animal Biotechnology and disease Control and prevention College of Animal Science and Veterinary MedicineShandong Agricultural UniversityTai’an 271018China

Background Breed identification is useful in a variety of biological *** identification usually involves two stages,i.e.,detection of breed-informative SNPs and breed *** both stages,there are several methods ***,what is the optimal combination of these methods remain *** this study,using the whole genome sequence data available for 13 cattle breeds from Run 8 of the 1,000 Bull Genomes Project,we compared the combinations of three methods(Delta,FST,and In)for breed-informative SNP detection and five machine learning methods(KNN,SVM,RF,NB,and ANN)for breed assignment with respect to different reference population sizes and difference numbers of most breed-informative *** addition,we evaluated the accuracy of breed identification using SNP chip data of different *** We found that all combinations performed quite well with identification accuracies over 95%in all ***,there was no combination which performed the best and robust across all *** proposed to inte-grate the three breed-informative detection methods,named DFI,and integrate the three machine learning methods,KNN,SVM,and RF,named *** found that the combination of these two integrated methods outperformed the other combinations with accuracies over 99%in most cases and was very robust in all *** accuracies from using SNP chip data were only slightly lower than that from using sequence data in most *** The current study showed that the combination of DFI and KSR was the optimal *** sequence data resulted in higher accuracies than using chip data in most ***,the differences were gener-ally *** view of the cost of genotyping,using chip data is also a good option for breed identification.

关键词： Breed identification Breed-informative SNPs Genomic breed composition Machine learning Whole genome sequence data

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Pyridoxine regulates hair follicle development via the PI3K/Akt, Wnt and Notch signalling pathways in rex rabbits

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animal Nutrition 2021年第4期7卷 1162-1172页

作者： Gongyan Liu Guangmin Cheng Yongcui Zhang Shuxia Gao Haitao Sun Liya Bai Shu Li Yanli Zhu Chunyang Wang Fuchang Li College of animal Science and Technology Shandong Agricultural UniversityShandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and PreventionTai'an 271018China Institute of animal Husbandry and Veterinary Shandong Academy of Agricultural SciencesShandong Key Laboratory of Animal Disease Control and BreedingJinan 251000China shandong Vocational animal Science and Veterinary College Weifang 261061China

This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular *** hundred 3-month-old Rex rabbits were randomly divided into 5 groups and fed diets supplemented with 0,5,10,20,or 40 mg/kg *** hair follicle density on the dorsal skin and the gene and protein expression levels of components of the phosphoinositide 3-kinase(PI3 K)/protein kinase B(PKB or Akt),Wnt,Notch and bone morphogenetic protein(BMP)signalling pathways were *** addition,free hair follicles were isolated from Rex rabbits and cultured with pyridoxine in vitro to measure hair shaft ***,dermal papilla cells(DPC)were isolated from the skin of Rex rabbits and cultured with pyridoxine in vitro to measure the gene and protein expression levels of components of the PI3 K/Akt,Wnt,Notch and BMP signalling *** results showed that the addition of dietary pyridoxine significantly increased the total follicle density,secondary follicle density,and secondary-to-primary ratio(S/P,P<0.05),that the growth ratio of hair stems was promoted by pyridoxine in basic culture medium,and that the growth length of tentacle hair follicles cultured in the pyridoxine group was longer than that in the control group(P<0.05).In addition,pyridoxine changed the DPC cycle progression and promoted cell proliferation,and appropriate concentrations of pyridoxine(10 and 20μmol/L)significantly inhibited cell apoptosis(P<0.05).Pyridoxine significantly affected the gene expression of components of the PI3 K/Akt,Wnt and Notch signalling pathways in the skin and DPC of Rex rabbits(P<0.05),increased the levels of phosphorylated catenin beta 1(CTNNB1)and Akt,and decreased the level of phosphorylated glycogen synthase kinase 3 beta(GSK-3β)(P<0.05).Therefore,the molecular mechanism by which pyridoxine promotes hair follicle density in Rex rabbits probably occurs through activation of the PI3 K/Akt,Wnt and Notch signa

关键词： Hair follicle development Pyridoxine Rex rabbit Dermal papilla cell

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Sanitary Evaluation of Rural Water Supply Projects—China,2020

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China CDC weekly 2022年第35期4卷 775-778页

作者： Yunting Xia Hongxing Li Chuanlong Xiong Rong Zhang shandong Provincial key laboratory of Communicable disease Control and prevention Department of Communicable Disease Control and PreventionShandong Center for Disease Control and PreventionJinanShandongChina

Summary What is already known about this topic?Over the last decade,the centralized water quality and supply have been substantially enhanced in rural ***,compared with the urban water supply,most of the rural Water Supply Projects(WaSPs)are small in scale,simple in engineering facilities,and poor in *** is added by this report?Most of the rural WaSPs have been basically guaranteed sustainable sources of *** measures should be taken to improve water disinfection effects,water losses control,and operational and maintenance *** WaSPs with water supply<3,000 m3/d need to be paid more *** are the implications for public health practice?Laws and regulations requiring rural WaSPs to carry out a sanitary evaluation should be *** should use tools such as World Health Organization Water Safety Plans to identify and control risks.

关键词： Rural rural carry

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Epidemiological Characteristics of Human Rabies——shandong Province,China,2010-2020

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China CDC weekly 2022年第35期4卷 793-797页

作者： Xiaomei Zhang Xueying Tian Bo Pang Zhiqiang Wang Wenji Zhai Xiaolin Jiang Zengqiang Kou Shujun Ding Xianjun Wang shandong Provincial key laboratory of Communicable disease Control and prevention Department of Communicable Disease Control and PreventionShandong Center for Disease Control and PreventionJinanShandongChina

Introduction:Rabies is a viral zoonotic disease that causes progressive and fatal inflammation in the *** has caused more than 5,000 human deaths in shandong Province since *** study aimed to analyze the epidemiological characteristics of human rabies in shandong Province from 2010 to 2020 and to provide a scientific basis for policy ***:The data of reported human rabies cases from 2010 to 2020 were obtained from China’s National Notifiable disease Reporting System,and data related to exposure and post-exposure prophylaxis(PEP)of the cases were acquired through case ***:A total of 414 human rabies cases were reported in shandong Province from 2010 to *** of the 414 total cases,87.20%were primarily farmers;83.10%were over 40 years old.70.29%(265/377)belonged to categoryⅢexposure;and 96.67%(377/390)were exposed to the virus through infected *** vaccine inoculation rate of these cases after exposure was only 8.85%;1.03%(4/390)had been vaccinated with rabies immunoglobulin,developing the disease 11 to 13 days after categoryⅢ***:Dogs were still the primary animal *** rabies patients died due to no or inadequate post-exposure *** inoculation rates for dogs should reach the target of 70%as soon as *** departments should improve the accessibility and quality of PEP;and improve the health literacy of the elderly in rural areas.

关键词： shandong category policy

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Therapeutic Potential of Anti-HIV RNA-loaded Exosomes

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Biomedical and Environmental Sciences 2018年第3期31卷 215-226页

作者： QIU Yong MA Jing ZENG Yi College of Life Science and bioengineering Beijing University of Technology State key laboratory of Infection disease prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention

Highly active antiretroviral therapy（HAART）is used globally and has significantly reduced the morbidity,mortality,and transmission of human immunodeficiency virus（HIV）-related ***,the attendant shortcomings such as toxic side effects,necessity of life-long therapy that is expensive, and inefficiency in eradicating latent viral infections have greatly limited the application of HAART.

关键词： HIV Therapeutic Potential of Anti-HIV RNA-loaded Exosomes RNA

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Influence of REV and ALV-J Co-Infection on Immunologic Function of T Lymphocytes and Histopathology in Broiler Chickens

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Agricultural Sciences in China 2010年第11期9卷 1667-1676页

作者： GUO Hui-jun, LI Hong-mei, CHENG Zi-qiang , LIU Jian-zhu and CUI Zhi-zhong key laboratory of animal Biotechnology and disease Control and prevention, College of Veternary Medicine, shandong Agricultural University, Tai’an 271018, P.R.China [a] key laboratory of animal Biotechnology and disease Control and prevention College of Veternary Medicine Shandong Agricultural University Tai'an 271018 P.R. China

The aim of present investigation is to study the effect of single- and co-infection with REV and ALV-J on T lymphocytes bioactivities and histopathology in broiler chickens. The bioactivities of blood and spleen T lymphocytes including lymphoproliferation responses, cytotoxicitic responses, and histopathology of spleen were detected in broiler chickens singly- or co-infected with REV and ALV-J at different days post inoculation and the virus expressions in spleen of infected broiler chickens were detected with immunofluorescence assay （IFA）. The results indicated that blood and spleen T lymphocytes proliferation responses and cytotoxicity in broilers infected with REV or/and ALV-J were inhibited in the whole observed period compared with controls. In the co-infected chickens they were highly inhibited than in the single-infected. The histopathology of spleen in infected chickens at 17 and 37 d post inoculation （dpi） indicated that cell interium increased, the numbers of lymphocytes decreased, and the regrowth were destroyed or decreased, especially more significantly at 17 than at 37 dpi. The different numbers of virus were detected in spleen lymphocytes in REV- infected and/or ALV-J-infected chickens. In the spleen of co-infected chicken, both REV and ALV-J were detected and the total numbers of viruses were more than in chickens singly-infected with REV or ALV-J. Thus, the co-effect of REV and ALV-J caused more immunosuppression on T lymphocytes bioactivities in broiler chickens than single-effect of ALV-J or REV, which contributed to the sever histopathology and the product of tumor cells. This study will be helpful for understanding the effect of co-infection with many viruses and control them in poultry.

关键词： reticuloendotheliosis virus (REV) J subgroup of avian leukosis virus (ALV-J) T lymphocyte activity,histopathology commercial broiler chickens

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