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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

Science China(Life sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li State Key laboratory for animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

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Accurate models and nutritional strategies for specific oxidative stress factors: Does the dose matter in swine production?

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Journal of animal Science and Biotechnology 2024年第2期15卷 519-534页

作者： Changming Hong Yujian Huang Shuting Cao Li Wang Xuefen Yang Shenglan Hu Kaiguo Gao Zongyong Jiang Hao Xiao State Key laboratory of Swine and Poultry Breeding Industry Ministry of Agriculture Key Laboratory of Animal Nutrition and Feed Science in South ChinaGuangdong Public Laboratory of Animal Breeding and NutritionGuangdong Provincial Key Laboratory of Animal Breeding and NutritionMaoming BranchGuangdong Laboratory for Lingnan Modern AgricultureGuangzhouChina institute of animal Science Guangdong Academy of Agricultural Sciences1 Dafeng 1st StreetGuangzhou 510640China

Oxidative stress has been associated with a number of physiological problems in swine,including reduced production efficiency.Recently,although there has been increased research into regulatory mechanisms and antioxidant strategies in relation to oxidative stress-induced pig production,it remains so far largely unsuccessful to develop accurate models and nutritional strategies for specific oxidative stress factors.Here,we discuss the dose and dose intensity of the causes of oxidative stress involving physiological,environmental and dietary factors,recent research models and the antioxidant strategies to provide theoretical guidance for future oxidative stress research in swine.

关键词： Accurate models Dose Nutritional strategies Oxidative stress Swine

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The chemical characteristics of different sodium iron ethylenediaminetetraacetate sources and their relative bioavailabilities for broilers fed with a conventional corn‑soybean meal diet

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Journal of animal Science and Biotechnology 2024年第2期15卷 826-843页

作者： Shengchen Wang Bingxin Wu Ling Zhu Weiyun Zhang Liyang Zhang We Wu Jiaqi Wu Yun Hu Tingting Li Xiaoyan Cui Xugang Luo College of animal Science and Technology Yangzhou UniversityYangzhou 225000People’s Republic of China Mineral Nutrition Research Division State Key Laboratory of Animal NutritionInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China

Background Our previous studies demonstrated that divalent organic iron(Fe)proteinate sources with higher complexation or chelation strengths as expressed by the greater quotient of formation(Qf)values displayed higher Fe bioavailabilities for broilers.Sodium iron ethylenediaminetetraacetate(NaFeEDTA)is a trivalent organic Fe source with the strongest chelating ligand EDTA.However,the bioavailability of Fe when administered as NaFeEDTA in broilers and other agricultural animals remains untested.Herein,the chemical characteristics of 12 NaFeEDTA products were determined.Of these,one feed grade NaFeEDTA(Qf=2.07×10^(8)),one food grade NaFeEDTA(Qf=3.31×10^(8)),and one Fe proteinate with an extremely strong chelation strength(Fe-Prot ES,Qf value=8,590)were selected.Their bioavailabilities relative to Fe sulfate(FeSO_(4)·7H_(2)O)for broilers fed with a conventional corn-soybean meal diet were evaluated during d 1 to 21 by investigating the effects of the above Fe sources and added Fe levels on the growth performance,hematological indices,Fe contents,activities and gene expressions of Fe-containing enzymes in various tissues of broilers.Results NaFeEDTA sources varied greatly in their chemical characteristics.Plasma Fe concentration(PI),transferrin saturation(TS),liver Fe content,succinate dehydrogenase(SDH)activities in liver,heart,and kidney,catalase(CAT)activity in liver,and SDH mRNA expressions in liver and kidney increased linearly(P<0.05)with increasing levels of Fe supplementation.However,differences among Fe sources were detected(P<0.05)only for PI,liver Fe content,CAT activity in liver,SDH activities in heart and kidney,and SDH mRNA expressions in liver and kidney.Based on slope ratios from multiple linear regressions of the above indices on daily dietary analyzed Fe intake,the average bioavailabilities of Fe-Prot ES,feed grade NaFeEDTA,and food grade NaFeEDTA relative to the inorganic FeSO_(4)·7H_(2)O(100%)for broilers were 139%,155%,and 166%,respectively.Conclusions The bioavailabilities of organic Fe sources

关键词： Broilers Chelation strengths Fe-containing enzymes NaFeEDTA Relative bioavailabilities

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Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

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Journal of animal Science and Biotechnology 2024年第3期15卷 1173-1189页

作者： Yan Lin Jiangnan Wu Yong Zhuo Bin Feng Zhengfeng Fang Shengyu Xu Jian Li Hua Zhao De Wu Lun Hua Lianqiang Che Key laboratory of animal Disease‑Resistance Nutrition Animal Nutrition InstituteSichuan Agricultural UniversityChengdu 611130SichuanChina

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

关键词： Ileum Intrauterine growth restriction Methyl donor Methylation Sows

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Development of small intestinal barrier function and underlying mechanism in Chinese indigenous and Duroc piglets during suckling and weaning periods

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animal Nutrition 2024年第1期16卷 429-442页

作者： Sujuan Ding Yating Cheng Md Abul Kalam Azad Qian Zhu Pan Huang Xiangfeng Kong CAS Key laboratory of Agro-ecological Processes in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process Institute of Subtropical Agriculture Chinese Academy of Sciences College of Advanced Agricultural sciences University of Chinese Academy of Sciences

This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning periods. Taoyuan black(TB), Xiangcun black(XB), and Duroc(DR) piglets(10 litters per breed; half male and half female) were selected for sampling to evaluate the intestinal barrier-related indexes and intestinal microbiota and metabolites at 1, 10, 21(weaned), and 24(3 d after weaning)d old. The results showed that weaning led to severe shedding of small intestinal microvilli and sparse microvilli arrangement. D-lactate level in the ileum of TB and XB piglets during suckling and weaning periods was lower(P < 0.01) than that of DR piglets, as well as the ileal diamine oxidase level at 1 d old.The expression level of mucin 1 was higher(P < 0.05) in the ileum of TB and XB piglets than that of DR piglets, and it was the highest in the ileum of TB piglets at 21 d old. The expression levels of mucin 2 and mucin 13 were higher(P < 0.10) in TB and XB piglets than those of DR piglets at 21 d old, whereas mucin2 and mucin 13 in the ileum of TB and XB piglets were higher(P < 0.05) than those of DR piglets at 24 d old. TB and XB piglets had a lower relative abundance of Escherichia＿Shigella at 21 and 24 d old, but they had higher Streptococcus at 1 and 24 d old than DR piglets(P < 0.01). Differential metabolites between the three breeds of piglets were mainly related to oxidative phosphorylation, steroid biosynthesis, and bile acid synthesis. Collectively, these findings suggest that different pig breeds present differences in the development of the small intestinal barrier function. Compared with DR piglets, TB and XB piglets had higher intestinal permeability during the suckling period and a stronger intestinal mechanical barrier after weaning. Moreover, intestinal microbiota and metabolites are the key factors for developing small intestinal barrier functions in different breeds of piglets.

关键词： Chinese indigenous piglet Duroc piglet Immune function Intestinal barrier function Weaning stress

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Mulberry leaf supplementation inhibits skatole deposition by regulating gut microbiota and upregulating liver cytochrome P4501A1 expression in finishing pigs

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animal Nutrition 2024年第1期16卷 34-44页

作者： Yuqing Sun Xiaoming Men Tianbao Lin Bo Deng Shi Zhong Jinxi Huo Kaipeng Qin Zhiqiang Lv Ziwei Xu Yougui Li institute of Sericulture and Tea Zhejiang Academy of Agricultural Sciences institute of animal Husbandry and Veterinary Science Zhejiang Academy of Agricultural Sciences

Skatole, a strong fecal odor substance, is generated through microbial degradation of tryptophan in the animal hindgut. It easily accumulates in adipose tissue and affects meat quality. In this study, the effect of mulberry leaf supplementation on skatole in finishing pigs was studied. In a 35-day trial, 20 finishing pigs (barrows and gilts) were fed with a basal diet or basal diet with 6% mulberry leaves. Growth performance of the pigs (n=10) was automatically recorded by a performance-testing feeder system and 8 pigs in each treatment were slaughtered and sampled for the remaining tests. Skatole and short-chain fatty acids were detected using HPLC and gas chromatography, respectively. Fecal microbiota were analyzed using 16S r RNA gene sequencing. The metabolomics analysis of feces and serum was performed with UHPLC-MS/MS. The major cytochrome P450 (CYP) enzymes that catalyze skatole degradation in the liver were tested by using RT-PCR and Western blot. Effects of major bioactive compounds in mulberry leaves on the CYP genes were verified in the hepatic cell line Hep G2 in an in vitro test (n=3). In finishing pigs, mulberry leaf supplementation had no significant effect on the average daily gain, average daily feed intake, and feed conversion ratio (P>0.05), but reduced skatole levels in feces, serum, and backfat (P<0.05), and increased acetic acid levels in feces (P=0.027). Mulberry leaf supplementation decreased the relative abundance of the skatole-producing bacteria Megasphaera and Olsenella (P<0.05). Indole-3acetic acid, the intermediate that is essential for skatole production, was significantly reduced in feces by mulberry leaf supplementation (P<0.05) and was positively correlated with skatole content in feces (P=0.004). In pigs treated with mulberry leaves, liver CYP1A1 expression was increased (P<0.05) and was negatively correlated with skatole content in backfat (P=0.045). The in vitro test demonstrated that mulberry leaf polyphenols and polysaccharides could directly stimulate CYP1A1 expression in h

关键词： Pig Skatole Mulberry leaf Microbiota Cytochrome P450

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Fermented calcium butyrate supplementation in post-peak laying hens improved ovarian function and tibia quality through the“gut-bone” axis

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animal Nutrition 2024年第1期16卷 350-362页

作者： Huaiyong Zhang Yongshuai Wang Yilu Wang Bin Wei Leilei Wang Minh Tu Nguyen Xiangyun Lv Yanqun Huang Wen Chen College of animal Science and Technology Key Laboratory of Animal Biochemistry and NutritionMinistry of AgricultureHenan Agricultural University laboratory for animal Nutrition and animal Product Quality Department of Animal Sciences and Aquatic EcologyGhent University Department of Agriculture and Forestry Hue University Charoen Pokphand Group Co. Ltd.

The compromised egg quality and leg abnormality during the end of the laying cycle(after 40 weeks)have been leading to poor animal welfare and substantial economic losses. Therefore, the effects of fermented calcium(Ca) butyrate, produced by fermentation by Clostridium butyricum, on production,eggshell quality, and tibial property of hens were explored. A total of 192 Hy-line brown laying hens at50-week-old were assigned to a basal diet or the basal diet with 300 mg/kg of the fermented Ca butyrate from 50 to 58 weeks of age. Each treatment had 6 replicates with 16 hens each. The diet supplemented with 300 mg/kg fermented Ca butyrate notably increased egg weight, ovarian follicle number, and eggshell strength(P = 0.072) as compared to the basal diet, which were associated with cytokine secretion, toll-like receptor signaling pathways, and intestinal immunity based on the RNA-seq data from the granulosa. Dietary Ca butyrate inclusion decreased the expression of ileal tumor necrosis factor-alpha and serum pro-inflammatory cytokine concentration, as well as increased the content of serum immunoglobulin A when compared to the basal diet(both P 0.05). In addition, the diet with fermented Ca butyrate reduced the number of osteoclasts in the proximal tibia and the level of C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker(P < 0.05), whereas it tended to increase the concentration of the procollagen type I N-terminal propeptide that reflects bone formation marker in serum. Moreover, the layers fed fermented Ca butyrate diets possessed higher(P < 0.05) bone area and trabecular number of the proximal tibia, yield load, and ultimate load than those that consumed basal diets. Collectively, dietary fermented Ca butyrate supplementation in post-peak layer diets improved the ovari

关键词： Fermented Ca butyrate Ovarian property Tibia metabolism Layer

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The evolving views of hematopoiesis:from embryo to adulthood and from in vivo to in vitro

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Journal of Genetics and Genomics 2024年第1期51卷 3-15页

作者： Yifan Zhang Feng Liu Shandong Provincial Key laboratory of animal Cell and Developmental Biology School of Life SciencesShandong UniversityQingdaoShandong 266237China State Key laboratory of Membrane Biology Institute of ZoologyInstitute for Stem Cell and RegenerationUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China

The hematopoietic system composed of hematopoietic stem and progenitor cells(HSPCs)and their differentiated lineages serves as an ideal model to uncover generic principles of cell fate transitions.From gastrulation onwards,there successively emerge primitive hematopoiesis(that produces specialized he-matopoietic cells),pro-definitive hematopoiesis(that produces lineage-restricted progenitor cells),and definitive hematopoiesis(that produces multipotent HSPCs).These nascent lineages develop in several transient hematopoietic sites and finally colonize into lifelong hematopoietic sites.The development and maintenance of hematopoietic lineages are orchestrated by cell-intrinsic gene regulatory networks and cell-extrinsic microenvironmental cues.Owing to the progressive methodology(e.g.,high-throughput lineage tracing and single-cell functional and omics analyses),our understanding of the developmental origin of hematopoietic lineages and functional properties of certain hematopoietic organs has been updated;meanwhile,new paradigms to characterize rare cell types,cell heterogeneity and its causes,and comprehensive regulatory landscapes have been provided.Here,we review the evolving views of HSPC biology during developmental and postnatal hematopoiesis.Moreover,we discuss recent advances in the in vitro induction and expansion of HSPCs,with a focus on the implications for clinical applications.

关键词： Hematopoietic stem and progenitor cell Developmental hematopoiesis Postnatal hematopoiesis In vitro hematopoiesis

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Message from animal models and experimental medicine for 2024-Striving for excellence with distinctive features

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animal Models and Experimental Medicine 2024年第1期7卷 1-1,I0002页

作者： Chuan Qin Chinese Association for laboratory animal sciences BeijingChina institute of laboratory animal sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Since its inception,animal Models and Experimental Medicine(AMEM)has received 632 articles in total from 52 countries and regions includ-ing China,Iran,the United States,India,Nigeria,Israel,Germany,Iraq,Italy,Japan,Australia,Bangladesh,Belgium,Brazil,and Canada,among others.AMEM has become an important international exchange plat-form for innovative research achievements in the field of laboratory animal science and basic medicine.

关键词： Israel Canada innovative

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Retinoic acid alleviates rotavirus-induced intestinal damage by regulating redox homeostasis and autophagic flux in piglets

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animal Nutrition 2024年第1期16卷 409-421页

作者： Xin Lai Aimin Wu Bing Yu Hui Yan Junqiu Luo Ping Zheng Jie Yu Daiwen Chen institute of animal Nutrition Sichuan Agricultural University Key laboratory for animal Disease-resistance Nutrition of China Ministry of Education Sichuan Agricultural University

Rotaviruses(RV) are a major cause of severe gastroenteritis, particularly in neonatal piglets. Despite the availability of effective vaccines, the development of antiviral therapies for RV remains an ongoing challenge. Retinoic acid(RA), a metabolite of vitamin A, has been shown to have anti-oxidative and antiviral properties. However, the mechanism by which RA exerts its intestinal-protective and antiviral effects on RV infection is not fully understood. The study investigates the effects of RA supplementation in Duroc × Landrace × Yorkshire(DLY) piglets challenged with RV. Thirty-six DLY piglets were assigned into six treatments, including a control group, RA treatment group with two concentration gradients(5and 15 mg/d), RV treatment group, and RV treatment group with the addition of different concentration gradients of RA(5 and 15 mg/d). Our study revealed that RV infection led to extensive intestinal architecture damage, which was mitigated by RA treatment at lower concentrations by increasing the villus height and villus height/crypt depth ratio(P < 0.05), enhancing intestinal stem cell signaling and promoting intestinal barrier functions. In addition, 15 mg/d RA supplementation significantly increased NRF2 and HO-1 protein expression(P < 0.05) and GSH content(P < 0.05), indicating that RA supplementation can enhance anti-oxidative signaling and redox homeostasis after RV challenge. Additionally,the research demonstrated that RA exerts a dual impact on the regulation of autophagy, both stimulating the initiation of autophagy and hindering the flow of autophagic flux. Through the modulation of autophagic flux, RA influence the progression of RV infection. These findings provide new insights into the regulation of redox hemostasis and autophagy by RA and its potential therapeutic application in RV infection.

关键词： Rotavirus Piglet Retinoic acid Intestinal barrier Redox hemostasis Autophagic flux

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