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Ferroptosis contributes to JEV-induced neuronal damage and neuroinflammation

Virologica Sinica 2024年第1期39卷 144-155页

作者： Wenjing Zhu Qi Li Yong Yin Huanchun Chen Youhui Si Bibo Zhu Shengbo Cao Zikai Zhao Jing Ye National Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhan430070China Frontiers Science center for Animal Breeding and sustainable production Huazhong Agricultural UniversityWuhan430070China the cooperative innovation center for sustainable pig production Huazhong Agricultural UniversityWuhan430070China Hubei Hongshan Laboratory Wuhan430070China

Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to numerous organ injuries and degenerative pathologies. Although studies have shown that a variety of cell death processes contribute to JEV-induced neuroinflammation and neuronal injury, there is currently limited research on the specific involvement of ferroptosis. In this study, we explored the neuronal ferroptosis induced by JEV infection in vitro and in vivo. Our results indicated that JEV infection induces neuronal ferroptosis through inhibiting the function of the antioxidant system mediated by glutathione (GSH)/glutathione peroxidase 4 (GPX4), as well as by promoting lipid peroxidation mediated by yes-associated protein 1 (YAP1)/long-chain acyl-CoA synthetase 4 (ACSL4). Further analyses revealed that JEV E and prM proteins function as agonists, inducing ferroptosis. Moreover, we found that treatment with a ferroptosis inhibitor in JEV-infected mice reduces the viral titers and inflammation in the mouse brains, ultimately improving the survival rate of infected mice. In conclusion, our study unveils a critical role of ferroptosis in the pathogenesis of JEV, providing new ideas for the prevention and treatment of viral encephalitis.

关键词： Japanese encephalitisvirus(JEV) Ferroptosis Neuron Lipid peroxidation Inflammatory response

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Hi-Tag:a simple and efficient method for identifying protein-mediated long-range chromatin interactions with low cell numbers

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Science China(Life Sciences) 2024年第5期67卷 1027-1034页

作者： Xiaolong Qi Lu Zhang Qiulin Zhao Peng Zhou Sai Xian Zhang Jingjin Li Zhuqing Zheng Yue Xiang Xueting Dai Zhe Jin Yaobang Jian Xinyun Li Liangliang Fu Shuhong Zhao Key Lab of Agricultural Animal Genetics Breeding and Reproduction of Ministry of Education and Key Laboratory of Swine Genetics and Breeding of Ministry of AgricultureCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China the cooperative innovation center for sustainable pig production Wuhan 430070China Hubei Hongshan Laboratory Frontiers Science Center for Animal Breeding and Sustainable ProductionWuhan 430070China

Protein-mediated chromatin interactions can be revealed by coupling proximity-based ligation with chromatin immunoprecipitation.However,these techniques require complex experimental procedures and millions of cells per experiment,which limits their widespread application in life science research.Here,we develop a novel method,Hi-Tag,that identifies high-resolution,long-range chromatin interactions through transposase tagmentation and chromatin proximity ligation(with a phosphorothioate-modified linker).Hi-Tag can be implemented using as few as 100,000 cells,involving simple experimental procedures that can be completed within 1.5 days.Meanwhile,Hi-Tag is capable of using its own data to identify the binding sites of specific proteins,based on which,it can acquire accurate interaction information.Our results suggest that Hi-Tag has great potential for advancing chromatin interaction studies,particularly in the context of limited cell availability.

关键词： Hi-Tag chromatin interactions transposase tagmentation chromatin proximity ligation low cell numbers

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Characterizing structural variants based on graph-genotyping provides insights into pig domestication and local adaption

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Journal of Genetics and Genomics 2024年第4期51卷 394-406页

作者： Xin Li Quan Liu Chong Fu Mengxun Li Changchun Li Xinyun Li Shuhong Zhao Zhuqing Zheng Key Lab of Agricultural Animal Genetics Breeding and Reproduction of Ministry of Education and Key Laboratory of Swine Genetics and Breeding of Ministry of AgricultureCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhanHubei 430070China Institute of Agricultural Biotechnology Jingchu University of TechnologyJingmenHubei 448000China the cooperative innovation center for sustainable pig production WuhanHubei 430070China Hubei Hongshan Laboratory WuhanHubei 430070China

Structural variants(SVs),such as deletions(DELs)and insertions(INSs),contribute substantially to pig genetic diversity and phenotypic variation.Using a library of SVs discovered from long-read primary assemblies and short-read sequenced genomes,we map pig genomic SVs with a graph-based method for re-genotyping SVs in 402 genomes.Our results demonstrate that those SVs harboring specific trait-associated genes may greatly shape pig domestication and local adaptation.Further characterization of SVs reveals that some population-stratified SVs may alter the transcription of genes by affecting regulatory elements.We identify that the genotypes of two DELs(296-bp DEL,chr7:52,172,101e52,172,397;278-bp DEL,chr18:23,840,143 e23,840,421)located in muscle-specific enhancers are associated with the expression of target genes related to meat quality(FSD2)and muscle fiber hypertrophy(LMOD2 and WASL)in pigs.Our results highlight the role of SVs in domestic porcine evolution,and the identified candidate functional genes and SVs are valuable resources for future genomic research and breeding programs in pigs.

关键词： pigs Structural variation Selection signatures Regulatory elements

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Ammonia-induced oxidative stress triggered proinflammatory response and apoptosis in pig lungs

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Journal of Environmental Sciences 2023年第4期126卷 683-696页

作者： Daojie Li Long Shen Di Zhang Xiaotong Wang Qiankun Wang Wenhao Qin Yun Gao Xiaoping Li Key Lab of Agricultural Animal Genetics Breeding and Reproduction of Ministry of EducationCollege of Animal Science and TechnologyThe Cooperative Innovation Center for Sustainable Pig ProductionHuazhong Agricultural UniversityWuhan 430070China College of Science Huazhong Agricultural UniversityWuhan 430070China College of Engineering The Cooperative Innovation Center for Sustainable Pig ProductionHuazhong Agricultural UniversityWuhan 430070China

Ammonia,a common toxic gas,is not only one of the main causes of haze,but also can enter respiratory tract and directly affect the health of humans and animals.pig was used as an animal model for exploring the molecular mechanism and dose effect of ammonia toxicity to lung.In this study,the apoptosis of type II alveolar epithelial cells was observed in high ammonia exposure group using transmission electron microscopy.Gene and protein expression analysis using transcriptome sequencing and western blot showed that low ammonia exposure induced T-cell-involved proinflammatory response,but high ammonia exposure repressed the expression of DNA repair-related genes and affected ion transport.Moreover,high ammonia exposure significantly increased 8-hydroxy-2-deoxyguanosine (8-OHdG) level,meaning DNA oxidative damage occurred.In addition,both low and high ammonia exposure caused oxidative stress in pig lungs.Integrated analysis of transcriptome and metabolome revealed that the up-regulation of LDHB and ND2 took part in high ammonia exposure-affected pyruvate metabolism and oxidative phosphorylation progress,respectively.Inclusion,oxidative stress mediated ammonia-induced proinflammatory response and apoptosis of porcine lungs.These findings may provide new insights for understanding the ammonia toxicity to workers in livestock farms and chemical fertilizer plants.

关键词： Ammonia Lung Proinflammatory response Oxidative stress Apoptosis Energy metabolism

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Paneth cells in farm animals:current status and future direction

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2263-2275页

作者： Chenbin Cui Lindeng Li Lin Wu Xinru Wang Yao Zheng Fangke Wang Hongkui Wei Jian Peng Department of Animal Nutrition and Feed Science College of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China the cooperative innovation center for sustainable pig production Wuhan 400700China

A healthy intestine plays an important role in the growth and development of farm animals.In small intestine,Paneth cells are well known for their regulation of intestinal microbiota and intestinal stem cells(ISCs).Although there has been a lot of studies and reviews on human and murine Paneth cells under intestinal homeostasis or disorders,little is known about Paneth cells in farm animals.Most farm animals possess Paneth cells in their small intestine,as identified by various staining methods,and Paneth cells of various livestock species exhibit noticeable differences in cell shape,granule number,and intestinal distribution.Paneth cells in farm animals and their antimicrobial peptides(AMPs)are susceptible to multiple factors such as dietary nutrients and intestinal infection.Thus,the comprehensive understanding of Paneth cells in different livestock species will contribute to the improvement of intestinal health.This review first summarizes the current status of Paneth cells in pig,cattle,sheep,horse,chicken and rabbit,and points out future directions for the investigation of Paneth cells in the reviewed animals.

关键词： Antimicrobial peptide Farm animal Intestinal organoid Intestine Paneth cell

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Multi‑omics analysis reveals gut microbiota‑ovary axis contributed to the follicular development difference between Meishan and Landrace×Yorkshire sows

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畜牧与生物技术杂志:英文版 2023年第5期14卷 1954-1968页

作者： Baoyang Xu Wenxia Qin Yuwen Chen Yimei Tang Shuyi Zhou Juncheng Huang Libao Ma Xianghua Yan State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070HubeiChina the cooperative innovation center for sustainable pig production Wuhan 430070HubeiChina Hubei Provincial Engineering Laboratory for pig Precision Feeding and Feed Safety Wuhan 430070HubeiChina

Background The mechanism by which Meishan(MS)sows are superior to white crossbred sows in ovarian follicle development remains unclear.Given gut microbiota could regulate female ovarian function and reproductive capacity,this study aimed to determine the role of gut microbiota-ovary axis on follicular development in sows.Methods We compared the ovarian follicular development,gut microbiota,plasma metabolome,and follicular fluid metabolome between MS and Landrace×Yorkshire(L×Y)sows.A H_(2)O_(2)-induced cell apoptosis model was used to evaluate the effects of multi-omics identified metabolites on the apoptosis of porcine ovarian granulosa cells in vitro.Results Compared with L×Y sows,MS sows have greater ovary weight and improved follicular development,including the greater counts of large follicles of diameter≥5 mm,secondary follicles,and antral follicles,but lesser atretic follicles.The ovarian granulosa cells in MS sows had alleviated apoptosis,which was indicated by the increased BCL-2,decreased caspases-3,and decreased cleaved caspases-3 than in L×Y sows.The ovarian follicular fluid of MS sows had higher concentrations of estradiol,progesterone,follicle-stimulating hormone,luteinizing hormone,and insulin like growth factor 1 than L×Y sows.Gut microbiota of MS sows formed a distinct cluster and had improved alpha diversity,including increased Shannon and decreased Simpson than those of L×Y sows.Corresponding to the enhanced function of carbohydrate metabolism and elevated short-chain fatty acids(SCFAs)in feces,the differential metabolites in plasma between MS and L×Y sows are also mainly enriched in pathways of fatty acid metabolism.There were significant correlations among SCFAs with follicular development,ovarian granulosa cells apoptosis,and follicular fluid hormones,respectively.Noteworthily,compared with L×Y sows,MS sows had higher follicular fluid SCFAs concentrations which could ameliorate H_(2)O_(2)-induced porcine granulosa cells apoptosis in vitro.Conclusion MS sows have more secondary and antral foll

关键词： Follicular development Granulosa cells apoptosis Gut microbiota Short-chain fatty acids Sows

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Identification of gut microbes associated with feed efficiency by daily-phase feeding strategy in growing-finishing pigs

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Animal Nutrition 2023年第1期12卷 42-53页

作者： Qin Jiang Chunlin Xie Lingli Chen Hongli Xiao Zhilian Xie Xiaoyan Zhu Libao Ma Xianghua Yan State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhanHubei 430070China The cooperative innovation center of sustainable pig production WuhanHubei 430070China Hubei Provincial Engineering Laboratory for pig Precision Feeding and Feed Safety Technology WuhanHubei 430070China

Feed efficiency is one of the most important issues for sustainable pig production.Daily-phase feeding(DPF)is a form of precision feeding that could improve feed efficiency in pigs.Gut microbiota can regulate host nutrient digestion,absorption,and metabolism.However,which key microbes may play a vital role in improving the feed efficiency during DPF remains unclear.In the present study,we used a DPF program compared to a three-phase feeding(TPF)program in growing-finishing pigs to investigate the effects of gut microbiota on feed efficiency.A total of 204 Landrace×Yorkshire pigs(75 d)were randomly assigned into 2 treatments.Each treatment was replicated 8 times with 13 to 15 pigs per replicate pen.pigs in the TPF group were fed with a commercial feeding program that supplied fixed feed for phasesⅠ,Ⅱ,andⅢ,starting at 81,101,and 132 d of age,respectively,and pigs in the DPF group were fed a blend of adjacent phase feed from 81 to 155 d at a gradual daily ratio and phaseⅢfeed from 155 to 180 d of age.Daily feed intake and body weight were recorded by a computerized device in the feeders.Feces and blood samples were collected from 1 pig per replicate at 155 and 180 d of age.The results showed that the DPF program remarkably improved the feed efficiency at 155 d(Ppigs.

关键词： Daily-phase feeding Feed efficiency Gut microbiota Nutrient metabolism pig

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Integrated analysis of multi-tissues lipidome and gut microbiome reveals microbiota-induced shifts on lipid metabolism in pigs

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Animal Nutrition 2022年第3期10卷 280-293页

作者： Chunlin Xie Xiaoyan Zhu Baoyang Xu Yaorong Niu Xuelei Zhang Libao Ma Xianghua Yan State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhanHubei 430070China The cooperative innovation center of sustainable pig production WuhanHubei 430070China Hubei Provincial Engineering Laboratory for pig Precision Feeding and Feed Safety Technology WuhanHubei 430070China

Lipid metabolism is very important for meat quality in pigs.Accumulating evidence shows that gut microbiota can contribute to this physiological process.However,the gut microbiota that function in lipid metabolism and adipogenesis remains unclear.Here,we compared the characteristics of fat deposition and gut microbial community between Laiwu pigs and Duroc(LandraceYorkshire)(DLY)pigs.Fecal microbiota transplantation(FMT)was performed to determine the possible impact of gut microbiota on lipid metabolism in pigs.An integrated analysis of the gut microbiome and lipidome of the small intestine,plasma,and liver was conducted to investigate the effects of FMT on host lipid metabolism.The comparative analysis of the gut microbiome showed higher abundance of Bacteroidetes(P=0.0018)while lower abundance of Firmicutes(P=0.012)in Laiwu pigs,and the microbial composition can be transferred from Laiwu pigs into DLY pigs.Transmission electron microscope and Oil red-O staining were performed to analyze the effects of FMT on lipid deposition in liver,the main target organ for lipid metabolism.The results showed that FMT significantly increased the number of lipid droplets(P=0.0035)and lipid accumulation(P=0.0026)in liver.Furthermore,integrated multi-tissues lipidome analysis demonstrated that the fatty acyls and glycerophospholipids were significantly increased(Ppigs.

关键词： pig Gut microbiota Lipidome Fecal microbiota transplantation Lipid metabolism

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Rice bran oil supplementation protects swine weanlings against diarrhea and lipopolysaccharide challenge

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 430-441页

作者： Juncheng HUANG Wenxia QIN Baoyang XU Haihui SUN Fanghua JING Yunzheng XU Jianan ZHAO Yuwen CHEN Libao MA Xianghua YAN State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070China the cooperative innovation center for sustainable pig production Wuhan 430070China Hubei Provincial Engineering Laboratory for pig Precision Feeding and Feed Safety Wuhan 430070China Yichun Dahaigui Life Science Co. Ltd.Yichun 336000China

Early weaned piglets suffer from oxidative stress and enteral infection,which usually results in gut microbial dysbiosis,serve diarrhea,and even death.Rice bran oil(RBO),a polyphenol-enriched by-product of rice processing,has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro.Here,we ascertained the proper RBO supplementation level,and subsequently determined its effects on lipopolysaccharide(LPS)-induced intestinal dysfunction in weaned piglets.A total of 168 piglets were randomly allocated into four groups of seven replicates(42 piglets each group,(21±1)d of age,body weight(7.60±0.04)kg,and half males and half females)and were given basal diet(Ctrl)or basal diet supplemented with 0.01%(mass fraction)RBO(RBO1),0.02%RBO(RBO2),or 0.03%RBO(RBO3)for 21 d.Then,seven piglets from the Ctrl and the RBO were treated with LPS(100μg/kg body weight(BW))as LPS group and RBO+LPS group,respectively.Meanwhile,seven piglets from the Ctrl were treated with the saline vehicle(Ctrl group).Four hours later,all treated piglets were sacrificed for taking samples of plasma,jejunum tissues,and feces.The results showed that 0.02%was the optimal dose of dietary RBO supplementation based on diarrhea,average daily gain,and average daily feed intake indices in early weaning piglets.Furthermore,RBO protected piglets against LPS-induced jejunal epithelium damage,which was indicated by the increases in villus height,villus height/crypt depth ratio,and Claudin-1 levels,as well as a decreased level of jejunal epithelium apoptosis.RBO also improved the antioxidant ability of LPS-challenged piglets,which was indicated by the elevated concentrations of catalase and superoxide dismutase,and increased total antioxidant capacity,as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma.Meanwhile,RBO improved the immune function of LPS-challenged weaned piglets,which was indicated by elevated immunoglobulin A(IgA),IgM,β-defensin-1,and lysozyme levels in the plasma.In addition,RBO supp

关键词： Rice bran oil Gut microbiota Weaned piglets Oxidative stress Lipopolysaccharide

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Lactobacillus gasseri LA39 promotes hepatic primary bile acid biosynthesis and intestinal secondary bile acid biotransformation

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第8期24卷 734-748页

作者： Jun HU Qiliang HOU Wenyong ZHENG Tao YANG Xianghua YAN National Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070China the cooperative innovation center for sustainable pig production Wuhan 430070China Hubei Provincial Engineering Laboratory for pig Precision Feeding and Feed Safety Technology Wuhan 430070Chin

A growing body of evidence has linked the gut microbiota to liver metabolism.The manipulation of intestinal microflora has been considered as a promising avenue to promote liver health.However,the effects of Lactobacillus gasseri LA39,a potential probiotic,on liver metabolism remain unclear.Accumulating studies have investigated the proteomic profile for mining the host biological events affected by microbes,and used the germ-free(GF)mouse model to evaluate host-microbe interaction.Here,we explored the effects of L.gasseri LA39 gavage on the protein expression profiles of the liver of GF mice.Our results showed that a total of 128 proteins were upregulated,whereas a total of 123 proteins were downregulated by treatment with L.gasseri LA39.Further bioinformatics analyses suggested that the primary bile acid(BA)biosynthesis pathway in the liver was activated by L.gasseri LA39.Three differentially expressed proteins(cytochrome P450 family 27 subfamily A member 1(CYP27A1),cytochrome P450 family 7 subfamily B member 1(CYP7B1),and cytochrome P450 family 8 subfamily B member 1(CYP8B1))involved in the primary BA biosynthesis pathway were further validated by western blot assay.In addition,targeted metabolomic analyses demonstrated that serum and fecalβ-muricholic acid(a primary BA),dehydrolithocholic acid(a secondary BA),and glycolithocholic acid-3-sulfate(a secondary BA)were significantly increased by L.gasseri LA39.Thus,our data revealed that L.gasseri LA39 activates the hepatic primary BA biosynthesis and promotes the intestinal secondary BA biotransformation.Based on these findings,we suggest that L.gasseri LA39 confers an important function in the gut‒liver axis through regulating BA metabolism.

关键词： Lactobacillus gasseri LA39 Liver Isobaric tags for relative and absolute quantitation(iTRAQ) Bile acid Germ-free mice

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