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animal Models and Experimental medicine 2024年第1期7卷 3-11页

作者： Hanwei Yue Lin Bai NHC Key laboratory of Human Disease comparative medicine Institute of Laboratory Animal SciencesCAMS and PUMCChao-yang DistrictBeijingChina

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient *** better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor *** exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and *** believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient *** characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid *** study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

关键词： antitumor antiviral CAR-T humanized immune system model humanized mice preclinical research

Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression-like behaviors in 5xFAD mice

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animal Models and Experimental medicine 2024年第3期7卷 347-361页

作者： Yanju Gong Mingfeng Li Min Liu Xinghan Wu Yanhong Li Chuan Qin Ling Zhang iNHC Key laboratory of Human Disease comparative medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInternational Center for Technology and lnnovation of Animal ModelComparative Medicine CenterInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PuMC)BeijingChina Changping National laboratory(CPNL) BeijingChina

Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD ***,the impact of ApoE4 on AD-associated depression-l ike behaviors and its underlying pathogenic mechanisms remain ***:This study developed a 5xFAD mouse model overexpressing human ApoE4(E4FAD).Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD *** in peripheral and central lipid metabolism,as well as the levels of serotonin(5-HT)andγ-aminobutyric acid(GABA)neurotransmitters in the prefrontal cortex,were *** addition,the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin(DHCR24/GSK3β/m TOR)and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor(PSD95/CaMK-II/BDNF)were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD ***:Compared with 5xFAD mice,E4FAD mice exhibited more severe depressionlike behaviors and cognitive *** mice also exhibited increased amyloid-beta deposition in the hippocampus,increased astrocyte numbers,and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal ***,lipid metabolism disorders were observed in E4FAD,manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood,decreased cholesterol level in the prefrontal cortex,and reduced expression of key enzymes and proteins related to cholesterol synthesis and *** expression of proteins related to the DHCR24/GSK3β/m TOR and PSD95/CaMK-II/BDNF pathways was also ***:This study found that ApoE4 overexpression exacerbates depressionlike behaviors in 5xFAD mice and confirmed that ApoE4 reduces co

关键词： 5xFAD mice Alzheimer's disease ApoE4 allele depression like

Prenatal cadmium exposure impairs neural tube closure via inducing excessive apoptosis in neuroepithelium

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Journal of Environmental Sciences 2024年第4期138卷 572-584页

作者： Shiyong Zhu Xuenan Li Xueyan Dai Jinlong Li College of Veterinary medicine Northeast Agricultural UniversityHarbin 150030China Key laboratory of the Provincial Education Department of Heilongjiang for Common animal Disease Prevention and Treatment Northeast Agricultural UniversityHarbin 150030China Heilongjiang Key laboratory for laboratory animals and comparative medicine Northeast Agricultural UniversityHarbin 150030China

Birth defects have become a public health *** hazardous environmental factors exposure to embryos could increase the risk of birth ***,a toxic environmental factor,can cross the placental barrier during *** woman may be subjected to cadmium before taking precautionary protective ***,the link between birth defects and cadmium remains *** exposure can induce excessive apoptosis in neuroepithelium during embryonic development *** exposure activated the p53 via enhancing the adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPK)and reactive oxygen species'(ROS)*** cadmium decreases the level of Paired box 3(Pax3)and murine double minute 2(Mdm2),disrupting the process of p53 *** p53 accumulation induced excessive apoptosis in neuroepithelium during embryonic development *** apoptosis led to the failure of neural tube *** study emphasizes that environmental materials may increase the health risk for *** caused the failure of neural tube closure during early embryotic *** women may be exposed by cadmium before taking precautionary protective actions,because of cadmium concentration-containing foods and environmental tobacco *** suggests that prenatal cadmium exposure is a threatening risk factor for birth defects.

关键词： Cadmium Neural tube closure Excessive apoptosis p53 Embryogenesis

Ultrasound-driven self-decomposition porphyrins as metal-free CO precursors for gas and sonodynamic synergistic therapy

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Science China Chemistry 2024年第5期67卷 1624-1635页

作者： Shuxin Liu Jinjuan Ma Xiang Xu Aiguo Wang Nan Zheng School of Chemical Engineering Dalian University of TechnologyDalian 116024China Department of comparative medicine laboratory animal Center Dalian Medical UniversityDalian 116000China Cancer Hospital of Dalian University of Technology Shenyang 116000China

Carbon monoxide(CO) is an endogenous therapeutic gas with an anti-tumor effect. The precise delivery and controlled release of CO in tumor tissues play crucial roles in anti-cancer treatment. However, efficient in situ generation of CO from metal-free COreleasing molecules(CORMs) remains a formidable challenge. Herein, we develop ultrasound(US)-driven self-decomposition porphyrin as organic and metal-free US-CORMs, which can spatiotemporally control the CO release(347 mmol CO/mol porphyrin) efficiently under physiologically harmless US conditions(1.0 MHz, 1.5 W/cm^(2), 50% duty cycle, 50 min). Moreover,porphyrin as a sonosensitizer can also generate reactive oxygen species(ROS) under US treatment to achieve sonodynamic therapy(SDT). Advanced functions of such porphyrin-based CORMs in CO gas-sonodynamic synergistic treatment have been demonstrated by evaluating the in vitro and in vivo anti-tumor effects.

关键词： porphyrin sonodynamic therapy metal-free CO precursors ultrasound-driven gas therapy

Essential oils improve nursery pigs'performance and appetite via modulation of intestinal health and microbiota

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animal Nutrition 2024年第1期16卷 174-188页

作者： Bi-Chen Zhao Tian-Hao Wang Jian Chen Bai-Hao Qiu Ya-Ru Xu Jin-Long Li College of Veterinary medicine Northeast Agricultural UniversityHarbin150030China Heilongjiang Key laboratory for laboratory animals and comparative medicine Northeast Agricultural UniversityHarbin150030China Key laboratory of the Provincial Education Department of Heilongjiang for Common animal Disease Prevention and Treatment Northeast Agricultural UniversityHarbin150030China

Optimal intestinal health and functionality are essential for animal health and performance,and simultaneously intestinal nutrient transporters and intestinal peptides are also involved in appetite and feed intake control *** the potential of essential oil(EO)in improving animal performance and improving feed palatability,we hypothesized that dietary supplementation of cinnamaldehyde and carvacrol could improve performance and appetite of nursery pigs by modulating intestinal health and ***(100 mg/kg),carvacrol(100 mg/kg),and their mixtures(including 50 mg/kg cinnamaldehyde and 50 mg/kg carvacrol)were supplemented into the diets of 240 nursery pigs for 42 d,and data related to performance were ***,the influence of EO on intestinal health,appetite and gut microbiota and their correlations were *** supplementation increased(P<0.05)the body weight,average daily gain(ADG)and average daily feed intake(ADFI)of piglets,and reduced(P<0.05)diarrhea rates in nursery ***,EO increased(P<0.05)the intestinal absorption area and the abundance of tight junction proteins,and decreased(P<0.05)intestinal permeability and local *** terms of intestinal development and the mucus barrier,EO promoted intestinal development and increased(P<0.05)the number of goblet ***,we found that piglets in the EO-supplemented group had upregulated(P<0.05)levels of transporters and digestive enzymes in the intestine,which were significantly associated with daily gain and feed *** addition,EO supplementation somewhat improved appetite in nursery pigs,increased the diversity of the gut microbiome and the abundance of beneficial bacteria,and there was a correlation between altered bacterial structure and appetite-related *** findings indicate that EO is effective in promoting growth performance and nutrient absorption as well as in regulating appetite by improving intestinal health and ba

关键词： Nursery pig Essential oil Intestinal health Appetite Microbiota

Infection with SARS-CoV-2 can cause pancreatic impairment

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin NHC Key laboratory of comparative medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Molecular medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing Key laboratory of Cardiometabolic Molecular medicine Peking UniversityBeijing 100871China State Key laboratory of Biomembrane and Membrane Biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of Engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China International Co-operation laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China National laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping National laboratory(CPNL) Beijing 102206China State Key laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of ***,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 ***-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and *** and limited phenotypic and histopathological changes were observed in adult *** proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio ***,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic *** contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

Repurposing Loperamide as an Anti-Infection Drug for the Treatment of Intracellular Bacterial Pathogens

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Engineering 2024年第8期39卷 180-193页

作者： Hongtao Liu Siqi Li Le Deng Zhenxu Shi Chenxiao Jiang Jingyan Shu Yuan Liu Xuming Deng Jianfeng Wang Zhimin Guo Jiazhang Qiu State Key laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases&Key laboratory of Zoonosis Research Ministry of EducationInstitute of ZoonosisCollege of Veterinary Medicine&Jilin UniversityChangchun 130062China Center for Pathogen Biology and Infectious Diseases The First Hospital of Jilin UniversityChangchun 130031China Jiangsu Co-Innovation Center for Prevention and Control of Important animal Infectious Diseases and Zoonoses Institute of Comparative MedicineCollege of Veterinary MedicineYangzhou UniversityYangzhou 225009China

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within *** rapid development and dissemination of antimicrobial–resistant strains have exacerbated this *** the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular ***,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(***).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of *** intracellular *** treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by *** addition,LPD treatment effectively protected against *** infection in Galleria mellonella and mouse ***,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial ***,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.

关键词： Intracellular bacteria US Food and Drug Administration(FDA)-approved drugs Drug repurposing Loperamide Autophagy Glycoprotein nonmetastatic melanoma protein B

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瘟疫与中医:我们为什么要关注?

Science Bulletin 2024年第11期69卷 1617-1622页

作者：熊一白鲍琳琳马艳张玲秦川黄璐琦 NHC Key laboratory of Human Disease comparative medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Basic Research in Clinical medicine China Academy of Chinese Medical SciencesBeijing 100700China China Academy of Chinese Medical Sciences Beijing 100700China National Resource Center for Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Changping National laboratory(CPNL) Beijing 102206China National Center for Technology and Innovation of animal Model Beijing 100021China

Wen-Yi refers to an acute infectious disease that is highly contagious and can cause widespread *** known as“Yi”or“Li”in the Chinese medicine(CM)literature,Wen-Yi diseases,such as corona virus disease 2019(COVID-1... 详细信息

关键词： acute diseases tuberculosis

Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

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Journal of animal Science and Biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin Jung Dae-Hyun Kim Jun-Koo Yi Jae-Jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-Jae Son Soo-Young Yum Won-Wu Lee Goo Jang laboratory of Theriogenology and Biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio Co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea comparative medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been considered as powerful tool in agricultural ***,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising ***,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in *** this point of view,electroporation in embryos has been risen as an *** First,editing efficiency of our electroporation methods were tested for *** of mutation on embryo was confirmed by T7E1 *** first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,*** case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for ***,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep *** recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double *** surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both *** These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively ***,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

Allelic reprogramming of chromatin states in human early embryos

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National Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai Han Zhao Zi-Jiang Chen Jiang Liu Keliang Wu Center for Reproductive medicine Shandong University CAS Key laboratory of Genome Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of Chinese Academy of Sciences CUHK-SDU Joint laboratory on Reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong Key laboratory of Reproductive Endocrinology of the Ministry of Education Shandong University Center for Reproductive medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS Center for Excellence in animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse *** allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early ***, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K27me3 chromatin accessibility