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Integrated liver proteomics and metabolomics identify metabolic pathways affected by pantothenic acid deficiency in Pekin ducks

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Animal Nutrition 2022年第4期11卷 1-14页

作者： Jing Tang Yongbao Wu Bo Zhang Suyun Liang Zhanbao Guo Jian Hu Zhengkui Zhou Ming Xie Shuisheng Hou State Key Laboratory of Animal Nutrition Key Laboratory of Animal(Poultry)Genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural Sciences100193BeijingChina

Pantothenic acid deficiency(PAD)in animals causes growth depression,fasting hypoglycemia and impaired lipid and glucose metabolism.However,a systematic multi-omics analysis of effects of PAD on hepatic function has apparently not been reported.We investigated liver proteome and metabolome changes induced by PAD to explain its effects on growth and liver metabolic disorders.Pekin ducks(1-dold,n=128)were allocated into 2 groups,with 8 replicates and 8 birds per replicate.For 16 d,all ducks had ad libitum access to either a PAD or a pantothenic acid adequate(control,CON)diet,formulated by supplementing a basal diet with 0 or 8 mg pantothenic acid/kg of diet,respectively.Liver enlargement,elevated liver glycogen concentrations and decreased liver concentrations of triglyceride and unsaturated fatty acids were present in the PAD group compared to the CON group.Based on integrated liver proteomics and metabolomics,PAD mainly affected glycogen synthesis and degradation,glycolysis and gluconeogenesis,tricarboxylic acid(TCA)cycle,peroxisome proliferator-activated receptor(PPAR)signaling pathway,fatty acid beta oxidation,and oxidative phosphorylation.Selected proteins were confirmed by Western blotting.Downregulation of proteins and metabolites involved in glycogen synthesis and degradation,glycolysis and gluconeogenesis implied that these processes were impaired in PAD ducks,which could have contributed to fasting hypoglycemia,liver glycogen storage,insufficient ATP production,and growth retardation.In contrast,PAD also upregulated proteins and metabolites involved in fatty acid beta oxidation,the TCA cycle,and oxidative phosphorylation processes in the liver;presumably compensatory responses to produce ATP.We inferred that PAD decreased liver triglyceride and unsaturated fatty acids by activating fatty acid beta oxidation and impairing unsaturated fatty acid synthesis.These findings contributed to our understanding of the mechanisms of PAD-induced changes in hepatic metabolism.

关键词： Pantothenic acid Hepatic metabolism Proteomics Metabolomics Hypoglycemia

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Dietary methionine deficiency stunts growth and increases fat deposition via suppression of fatty acids transportation and hepatic catabolism in Pekin ducks

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Journal of Animal Science and Biotechnology 2022年第6期13卷 1871-1886页

作者： Yongbao Wu Jing Tang Zhiguo Wen Bo Zhang Junting Cao Lulu Zhao Zhanbao Guo Ming Xie Zhengkui Zhou Shuisheng Hou State Key Laboratory of Animal Nutrition Key Laboratory of Animal(Poultry)Genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsInstitute of Animal SciencesChinese Academy of Agricultural SciencesBeijing 100193China Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs Institute of Feed ResearchChinese Academy of Agricultural SciencesBeijing 100081China

Background:Although methionine(Met),the first-limiting dietary amino acid,has crucial roles in growth and regulation of lipid metabolism in ducks,mechanisms underlying are not well understood.Therefore,the objective was to use dietary Met deficiency to investigate the involvement of Met in lipid metabolism and fat accumulation of Pekin ducks.Methods:A total of 150 male Pekin ducks(15-d-old,558.5±4.4 g)were allocated into 5 groups(6 replicates with 5 birds each)and fed corn and soybean meal-based diets containing 0.28%,0.35%,0.43%,0.50%,and 0.58%Met,respectively,for 4 weeks.Met-deficient(Met-D,0.28%Met)and Met-adequate(Met-A,0.43%Met)groups were selected for subsequent molecular studies.Serum,liver,and abdominal fat samples were collected to assess the genes and proteins involved in lipid metabolism of Pekin ducks and hepatocytes were cultured in vivo for verification.Results:Dietary Met deficiency caused growth depression and excess fat deposition that were ameliorated by feeding diets with adequate Met.Serum triglyceride and non-esterified fatty acid concentrations increased(P<0.05),whereas serum concentrations of total cholesterol,low density lipoprotein cholesterol,total protein,and albumin decreased(P<0.05)in Met-D ducks compared to those in Met-A ducks.Based on hepatic proteomics analyses,dietary Met deficiency suppressed expression of key proteins related to fatty acid transport,fatty acid oxidation,tricarboxylic acid cycle,glycolysis/gluconeogenesis,ketogenesis,and electron transport chain;selected key proteins had similar expression patterns verified by qRT-PCR and Western blotting,which indicated these processes were likely impaired.In vitro verification with hepatocyte models confirmed albumin expression was diminished by Met deficiency.Additionally,in abdominal fat,dietary Met deficiency increased adipocyte diameter and area(P<0.05),and down-regulated(P<0.05)of lipolytic genes and proteins,suggesting Met deficiency may suppress lipolysis in adipocyte.Conclusion:Taken together,these data demonstrated th

关键词： Fat deposition Hepatic catabolism Methionine deficiency Pekin duck Proteomics

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Strategies to improve genomic predictions for 35 duck carcass traits in an F2 population

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畜牧与生物技术杂志:英文版 2023年第5期14卷 1854-1868页

作者： Wentao Cai Jian Hu Wenlei Fan Yaxi Xu Jing Tang Ming Xie Yunsheng Zhang Zhanbao Guo Zhengkui Zhou Shuisheng Hou Institute of Animal Science Chinese Academy of Agricultural SciencesBeijing 100193China Shandong New Hope Liuhe Group Co. Ltd.Qingdao 266108China College of Animal Science and Technology Qingdao Agricultural UniversityQingdao 266109China College of Animal Science and Technology Beijing University of AgricultureBeijing 102206China

Background Carcass traits are crucial for broiler ducks,but carcass traits can only be measured postmortem.Genomic selection(GS)is an effective approach in animal breeding to improve selection and reduce costs.However,the performance of genomic prediction in duck carcass traits remains largely unknown.Results In this study,we estimated the genetic parameters,performed GS using different models and marker densi-ties,and compared the estimation performance between GS and conventional BLUP on 35 carcass traits in an F2 population of ducks.Most of the cut weight traits and intestine length traits were estimated to be high and moder-ate heritabilities,respectively,while the heritabilities of percentage slaughter traits were dynamic.The reliability of genome prediction using GBLUP increased by an average of 0.06 compared to the conventional BLUP method.The Permutation studies revealed that 50K markers had achieved ideal prediction reliability,while 3K markers still achieved 90.7%predictive capability would further reduce the cost for duck carcass traits.The genomic relationship matrix nor-malized by our true variance method instead of the widely used 2pi(1-pi)could achieve an increase in prediction reliability in most traits.We detected most of the bayesian models had a better performance,especially for BayesN.Compared to GBLUP,BayesN can further improve the predictive reliability with an average of 0.06 for duck carcass traits.Conclusion This study demonstrates genomic selection for duck carcass traits is promising.The genomic prediction can be further improved by modifying the genomic relationship matrix using our proposed true variance method and several Bayesian models.Permutation study provides a theoretical basis for the fact that low-density arrays can be used to reduce genotype costs in duck genome selection.

关键词： Bayesian model Carcass traits Duck Genome prediction Genomic relationship matrix Mark density

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Co-delivery of Cisplatin and Chlorin e6 by Poly(phosphotyrosine)for Synergistic Chemotherapy and Photodynamic Therapy

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Chinese Journal of Chemistry 2022年第20期40卷 2428-2436页

作者： Haisen zhou Yaoyi Wang Yingqin Hou zhengkui Zhang Qi Wang Xiaodong Tian Hua Lu Beijing National Laboratory for Molecular Sciences Center for Soft Matter Science and EngineeringKey Laboratory of Polymer Chemistry and Physics of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing100871 China Department of General Surgery Peking University First HospitalBeijing100034 China

Nanoscale drug delivery systems(NDDSs)have emerged as promising carriers for combinational therapy by co-delivery of multiple drugs and modalities.However,most co-delivery systems require the use of complicated materials and formulations.Herein,we report the single use of a polymeric material,namely mPEG-block-poly(phosphotyrosine)(mPEG-b-PpY),as a multi-functional carrier for the facile fabrication of NDDS Pt/Ce6@mPEG-b-PpY(PtCeNP)for the co-delivery of cisplatin and photosensitizer chlorin e6(Ce6)via phosphato-platinum coordination andπ-πstacking,respectively.PtCeNP improves the solubility,cellular uptake,and bioavailability of both parental drugs,and showed strong synergistic antitumor efficacy both in vitro and in vivo through combined chemo-photodynamic therapy.Our results indicate that PpY is a biocompatible,multifunctional,and promising carrier material suitable for a variety of drugs and may simplify the design for co-delivery systems.

关键词： Drug delivery Poly(phosphotyrosine) Block copolymers Nanoparticles Combinational chemo-photodynamic therapy

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Effect of riboflavin deficiency on intestinal morphology,jejunum mucosa proteomics,and cecal microbiota of Pekin ducks

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Animal Nutrition 2023年第1期12卷 215-226页

作者： Yaxi Xu Bo Zhang Rui Zhao Kexin Gao Suyun Liang Yongbao Wu Yongsheng Hao Dapeng Liu Zhanbao Guo Jian Hu Zhengkui Zhou Ming Xie Jing Tang State Key Laboratory of Animal Nutrition Key Laboratory of Animal(Poultry)Genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsInstitute of Animal ScienceChinese Academy of Agricultural SciencesBeijing100193China

This study was to determine the effects of riboflavin deficiency(RD)on intestinal development,jejunum mucosa proteome,cecal short-chain fatty acids(SCFA)profiling,and cecal microbial diversity and community of starter Pekin ducks.Male white Pekin ducks(1 d old,n=240)were allocated into 2 groups,with 12 replicates and 10 birds per replicate in each group.For 21 d,all ducks had ad libitum access to either an RD or a riboflavin adequate(control,CON)diet,formulated by supplementing a basal diet with 0 or 10 mg riboflavin per kg of diet,respectively.Compared to the CON group,growth retardation,high mortality,and poor riboflavin status were observed in the RD group.Furthermore,RD reduced the villus height and the ratio of villus height to crypt depth of jejunum and ileum(P<0.05),indicating morphological alterations of the small intestine.In addition,dietary RD enhanced relative cecum weight and decreased cecal SCFA concentrations(P<0.05),including propionate,isobutyrate,butyrate,and isovalerate.The jejunum mucosa proteomics showed that 208 proteins were upregulated and 229 proteins were downregulated in the RD group compared to those in the CON group.Among these,RD mainly suppressed intestinal absorption and energy generation processes such as glycolysis and gluconeogenesis,fatty acid beta oxidation,tricarboxylic acid cycle,and oxidative phosphorylation,leading to impaired ATP generation.In addition,RD decreased the community richness and diversity of the bacterial community in the cecum of ducks.Specifically,RD reduced the abundance of butyrate-producing bacteria in the cecum(P<0.05),such as Eubacterium coprostanoligenes,Prevotella and Faecalibacterium.Dietary RD resulted in growth depression and intestinal hypofunction of Pekin ducks,which could be associated with impaired intestinal absorption and energy generation processes in intestinal mucosa,as well as gut microbiota dysbiosis.These findings contribute to our understanding of the mechanisms of intestinal hypofunction due to RD.

关键词： Riboflavin Deficiency Intestinal morphology Proteomics Cecal microbiota Short-chain fatty acids

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Exosomal miR-485-3p derived from pancreatic ductal epithelial cells inhibits pancreatic cancer metastasis through targeting PAK1

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Chinese Medical Journal 2022年第19期135卷 2326-2337页

作者： Mingzhe Li Jiaxin zhou zhengkui Zhang Jisong Li Feng Wang Ling Ma Xiaodong Tian Zebin Mao Yinmo Yang Department of General Surgery Peking University First HospitalBejing 100034China Department of Urology Sir Run Run Shaw HospitalZhejang UniversityHangzhouZhejiang 310016China Department of Gastrointestinal Surgery Sichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalChengduSichuan 610072China Department of Surgical Oncology Peking University Ninth School of Clinical Medicine(Bejing Shijitan HospitalCapital Medical University)Bejing 100038China Department of Medical Biochemistry and Molecular Biology Peking University Health Science CenterBeijing 100191China.

Background:Cell competition is an important feature in pancreatic cancer(PC)progression,but the underlying mechanism remains elusive.This study aims to explore the role of exosomes derived from normal pancreatic ductal epithelial cells involved in PC progression.Methods:PC cells and pancreatic stellate cells(PSCs)were treated with exosomes isolated from pancreatic ductal epithelial cells.Cell proliferation was assessed by CCK8 assays.Cell migration and invasion were assessed by Transwell assays.PC and matched adjacent non-tumor tissue specimens were obtained from 46 patients pathologically diagnosed with PC at Peking University First Hospital from 2013 to 2017.Tissue miR-485-3p and p21-activated kinase-1(PAK1)expression was examined by real-time polymerase chain reaction(RT-PCR),and the relationship of the two was analyzed using Pearman’s product-moment correlation.The clinical significance of miR-485-3p was analyzed using the Chi-square test,Wilcoxon rank-sum test,and Fisher exact probability,respectively.The binding of miR-485-3p to PAK15’-untranslated region(5’-UTR)was examined by luciferase assay.PC cells were xenografted into nude mice as a PC metastasis model.Results:Exosomes from pancreatic ductal epithelial cells suppressed PC cell migration and invasion as well as the secretion and migration of PSCs.MiR-485-3p was enriched in the exosomes of pancreatic ductal epithelial cells but deficient in those of PC cells and PSCs,in accordance with the lower level in PSCs and PC cells than that in pancreatic ductal cells.And the mature miR-485-3p could be delivered into these cells by the exosomes secreted by normal pancreatic duct cells,to inhibit PC cell migration and invasion.Clinical data analysis showed that miR-485-3p was significantly decreased in PC tissues(P<0.05)and was negatively associated with lymphovascular invasion(P=0.044).As a direct target of miR-485-3p,PAK1 was found to exert an inhibitory effect on PC cells,and there was a significantly negative correlation between the expression levels of miR-4

关键词： Pancreatic neoplasms Cell competition Exosomes miR-485-3p p21-activated kinase-1

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Chloroplast DNA Underwent Independent Selection from Nuclear Genes during Soybean Domestication and Improvement

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Journal of Genetics and Genomics 2016年第4期43卷 217-221页

作者： Chao Fang Yanming Ma Lichai Yuan Zheng Wang Rui Yang Zhengkui Zhou Tengfei Liu Zhixi Tian State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing University of Agriculture Beijing 102206China The Institute of Medicinal Plant Development Chinese Academy of Medical SciencesBeijing 100193China

The chloroplast is one of the most important organs in plants because of its essential role in photosynthesis.Studies have shown that the chloroplast was once a free-living cyanobacteria and was integrated into the host species through endosymbiosis（Goksoyr.1967）.after which a large number of its genes had been donated to the host nuclear genome（Heins and Soll, 1998）.

关键词： gene Chloroplast DNA Underwent Independent Selection from Nuclear Genes during Soybean Domestication and Improvement than DNA

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The interactions between cGAS-STING pathway and pathogens

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1657-1671页

作者： Zhangliang Cheng Tong Dai Xuelin He zhengkui Zhang Feng Xie Shuai Wang Long Zhang Fangfang zhou Institutes of Biology and Medical Science Soochow University215123 SuzhouP.R.China MOE Laboratory of Biosystems Homeostasis&Protection and Innovation Center for Cell Signaling Network Life Sciences InstituteZhejiang University310058 HangzhouChina Kidney Disease Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

Cytosolic DNA is an indicator of pathogen invasion or DNA damage.The cytosolic DNA sensor cyclic guanosine monophosphateadenosine monophosphate(cGAMP)synthase(cGAS)detects DNA and then mediates downstream immune responses through the molecule stimulator of interferon genes(STING,also known as MITA,MPYS,ERIS and TMEM173).Recent studies focusing on the roles of the cGAS-STING pathway in evolutionary distant species have partly sketched how the mammalian cGAS-STING pathways are shaped and have revealed its evolutionarily conserved mechanism in combating pathogens.Both this pathway and pathogens have developed sophisticated strategies to counteract each other for their survival.Here,we summarise current knowledge on the interactions between the cGAS-STING pathway and pathogens from both evolutionary and mechanistic perspectives.Deeper insight into these interactions might enable us to clarify the pathogenesis of certain infectious diseases and better harness the cGAS-STING pathway for antimicrobial methods.

关键词： pathogens invasion interferon

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;he regulation of TGF-β/SMAD signaling by protein deubiquitination

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Protein & Cell 2014年第7期5卷 503-517页

作者： Juan Zhang Xiaofei Zhang Feng Xie zhengkui Zhang Hans van Dam Long Zhang Fangfang zhou Life Sciences Institute Zhejiang University Hangzhou 310058 China Department of Molecular Cell Biology Cancer Genomics Centre Netherlands and Centre of Biomedical Genetics Leiden University Medical Center Postbus 9600 2300 RC Leiden The Netherlands

Transforming growth factor-β （TGF-β） members are key cytokines that control embryogenesis and tissue homeostasis via transmembrane TGF-β type II （TβR II） and type I （TβRI） and serine/threonine kinases receptors. Aberrant activation of TGF-β signaling leads to diseases, including cancer. In advanced cancer, the TGF-β/SMAD pathway can act as an oncogenic factor driving tumor cell invasion and metastasis, and thus is considered to be a therapeutic target. The activity of TGF-β/SMAD pathway is known to be regulated by ubiquitination at multiple levels. As ubiquitination is reversible, emerging studies have uncovered key roles for ubiquitin-removals on TGF-β signaling components by deubiquitinating enzymes （DUBs）. In this paper, we summarize the latest findings on the DUBs that control the activity of the TGF-β signaling pathway. The regula- tory roles of these DUBs as a driving force for cancer progression as well as their underlying working mech- anisms are also discussed.

关键词： TGF-β TβRI SMAD DUB ubiquitin deubiquitination

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新时代语文教育改革大发展的创新之路

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中国教育科学（中英文） 2020年第6期3卷 3-11页

作者：周正逵人民教育出版社人民教育出版社课程教材研究所

明确发展方向是语文教育改革的百年大计,现代化的语文教育必须坚持以民族化为基础,以科学化为指导,把民族化与科学化结合起来,把古今中外行之有效的传统经验与讲求效率的科学方法结合起来,才能创建中国特色现代语文教育和语文教材新体... 详细信息

明确发展方向是语文教育改革的百年大计,现代化的语文教育必须坚持以民族化为基础,以科学化为指导,把民族化与科学化结合起来,把古今中外行之有效的传统经验与讲求效率的科学方法结合起来,才能创建中国特色现代语文教育和语文教材新体系。摆脱“西化”阴影是语文教育改革的治本之策,增强文化自信是语文教育改革的坚定信念,找回中国特色是语文教育改革的主要目标,教材整体改革是语文教育改革的中心环节,开展科学实验是语文教育改革的必由之路,提高教师素养是语文教育改革的决定因素,加强统一领导是语文教育改革的根本保证。

关键词：语文教育现代化科学化民族化教材改革教师素养

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