Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the ext...Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.展开更多
Background:A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits.However,the genome-wide chr...Background:A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits.However,the genome-wide chromatin accessibility has been only reported in limited tissue types in pigs.Results:Here we report a genome-wide landscape of chromatin accessibility of 20 tissues in two female pigs at ages of 6 months using ATAC-seq,and identified 557,273 merged peaks,which greatly expanded the pig regulatory ele-ment repository.We revealed tissue-specific regulatory elements which were associated with tissue-relevant biologi-cal functions.We identified both positive and negative significant correlations between the regulatory elements and gene transcripts,which showed distinct distributions in terms of their strength and distances from corresponding genes.We investigated the presence of transposable elements(TEs)in open chromatin regions across all tissues,these included identifications of porcine endogenous retroviruses(PERVs)exhibiting high accessibility in liver and homology of porcine specific virus sequences to universally accessible transposable elements.Furthermore,we prior-itized a potential causal variant for polyunsaturated fatty acid in the muscle.Conclusions:Our data provides a novel multi-tissues accessible chromatin landscape that serve as an important resource for interpreting regulatory sequences in tissue-specific and conserved biological functions,as well as regula-tory variants of loci associated with complex traits in pigs.展开更多
Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals...Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.展开更多
Dear Editor,Mitochondria are the center of cellular energy generation and free radical metabolism,with important functions in regulating intracellular calcium levels,cell apoptosis,cell cycle and epigenetic modificati...Dear Editor,Mitochondria are the center of cellular energy generation and free radical metabolism,with important functions in regulating intracellular calcium levels,cell apoptosis,cell cycle and epigenetic modifications.Mitochondrial DNA copy number(mtDNA-CN)is an indicator of mitochondrial biogenesis and has been associated with several diseases,such as cardiovascular disease,depression,chronic kidney disease and aging in humans(Clyde,2022).展开更多
Correction:aBIOTECH(2022)3:212–223 https://doi.org/10.1007/s42994-022-00082-5 The copyright holder for this article was incorrectly given as’Agricultural Information Institute,Chinese Academy of Agricultural Science...Correction:aBIOTECH(2022)3:212–223 https://doi.org/10.1007/s42994-022-00082-5 The copyright holder for this article was incorrectly given as’Agricultural Information Institute,Chinese Academy of Agricultural Sciences’but should have been’The Authors’.This article was originally published with the incorrect licence;it should have been:Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons licence,unless indicated otherwise in a credit line to the material.展开更多
Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical...Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical PHCZs to investigate their negative consequences,along with alternations in gutmicrobiota to indicate underlyingmechanisms.In female mice,the relative liver weight ratio increased after four PHCZs exposure;2-bromocarbazole(2-BCZ)increased urine glucose level;3-bromocarbazole(3-BCZ)decreased the glucose and total cholesterol levels;3,6-dichlorocarbazole(3,6-DCCZ)decreased glucose level.The only disturbed biochemical index in male mice was the promoted alkaline phosphatase(ALP)level by 3,6-DCCZ.We also found that the differential blood biochemical indices were correlated with gut microbiota.3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice,which were correlated with metabolic disorders.Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity andmetabolic disordersmay be due to their dioxin-like potentials and endocrine disrupting activities,and the gender differences might result from their estrogenic activities.Overall,data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.展开更多
Rational construction of high-efficiency electrocatalysts for oxygen evolution reaction(OER)is critical for renewable-energy technologies,but it is highly challenging to rationally regulate their surface structures to...Rational construction of high-efficiency electrocatalysts for oxygen evolution reaction(OER)is critical for renewable-energy technologies,but it is highly challenging to rationally regulate their surface structures to improve the OER performance.Herein,we proposed a“model-etching”strategy to investigate chemical etching of CO_(3)O_(4).The cubic CO_(3)O_(4)nanocrystals enclosed by well-defined facets are synthesized as model crystals,whose uniform surface structures allow us to study the etching mechanism at atomic level.Etching kinetics study together with DFT calculations discloses that{111}facets,the highly active facets for OER,serve as etch-stop facets in the etching reaction and H_(2)SO_(4)molecules play a special role in creating surface Co2^(+),the active center of OER.These results direct us to rationally optimize the surface structures of CO_(3)O_(4) to develop highly active OER electrocatalysts.The favorable performance of overpotential(η)and the Tafel slope decrease even to 268 mV@10 mA·cm−2 and 74 mV·dec−1,respectively.In general,our study shows that chemical etching of model crystals could help us rationally construct high-efficiency electrocatalysts.展开更多
The limited knowledge of genomic noncoding and regulatory regions has restricted our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterized the spatiotemporal lan...The limited knowledge of genomic noncoding and regulatory regions has restricted our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterized the spatiotemporal landscape of putative enhancers and promoters and their target genes by combining H3K27ac-targeted Ch IP-Seq and RNA-Seq in fetal(prenatal days 74–75) and adult(postnatal days 132–150) tissues(brain, liver, heart, muscle and small intestine) sampled from Asian aboriginal Bama Xiang and European highly selected Large White pigs of both sexes. We identified 101,290 H3K27ac peaks, marking 18,521promoters and 82,769 enhancers, including peaks that were active across all tissues and developmental stages(which could indicate safe harbor locus for exogenous gene insertion) and tissue-and developmental stage-specific peaks(which regulate gene pathways matching tissue-and developmental stage-specific physiological functions). We found that H3K27ac and DNA methylation in the promoter region of the XIST gene may be involved in X chromosome inactivation and demonstrated the utility of the present resource for revealing the regulatory patterns of known causal genes and prioritizing candidate causal variants for complex traits in pigs. In addition, we identified an average of 1,124 super-enhancers per sample and found that they were more likely to show tissue-specific activity than ordinary peaks. We have developed a web browser to improve the accessibility of the results(http://segtp.jxau.edu.cn/pencode/?genome=sus Scr11).展开更多
Assays for transposase-accessible chromatin through high-throughput sequencing(ATAC-seq)are effective tools in the study of genome-wide chromatin accessibility landscapes.With the rapid development of single-cell tech...Assays for transposase-accessible chromatin through high-throughput sequencing(ATAC-seq)are effective tools in the study of genome-wide chromatin accessibility landscapes.With the rapid development of single-cell technology,open chromatin regions that play essential roles in epigenetic regulation have been measured at the single-cell level using single-cell ATAC-seq approaches.The application of scATAC-seq has become as popular as that of scRNA-seq.However,owing to the nature of scATAC-seq data,which are sparse and noisy,processing the data requires different methodologies and empirical experience.This review presents a practical guide for processing scATAC-seq data,from quality evaluation to downstream analysis,for various applications.In addition to the epigenomic profiling from scATAC-seq,we also discuss recent studies in which the function of non-coding variants has been investigated based on cell type-specific cis-regulatory elements and how to use the by-product genetic information obtained from scATAC-seq to infer single-cell copy number variants and trace cell lineage.We anticipate that this review will assist researchers in designing and implementing scATAC-seq assays to facilitate research in diverse fields.展开更多
基金supported by the National Key R&D Program of China(2022YFA1304204)National Natural Science Foundation of China(31772579).
文摘Background Sex hormones play important roles in the estrus return of post-weaning sows.Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota.However,the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown.Results In this study,we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows.Using metagenomic sequencing data from 85 fecal samples,we identified 37 bacterial species that were significantly associated with estrus return.Normally returning sows were characterized by increased abundances of L.reuteri and P.copri and decreased abundances of B.fragilis,S.suis,and B.pseudolongum.The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome.The results were confirmed in a validation cohort.Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis.An integrated analysis of differential bacterial species,metagenome,and fecal metabolome provided evidence that normal return-associated bacterial species L.reuteri and Prevotella spp.participated in the degradation of pregnenolone,progesterone,and testosterone,thereby promoting estrogen biosynthesis.Furthermore,the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return.Conclusions An integrated analysis of differentially abundant bacterial species,metagenome,and fecal metabolome revealed the involvement of L.reuteri and Prevotella spp.in sow estrus return.These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones,suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.
基金supported by National Key Research and Development Program of China(2021YFF1000601).
文摘Background:A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits.However,the genome-wide chromatin accessibility has been only reported in limited tissue types in pigs.Results:Here we report a genome-wide landscape of chromatin accessibility of 20 tissues in two female pigs at ages of 6 months using ATAC-seq,and identified 557,273 merged peaks,which greatly expanded the pig regulatory ele-ment repository.We revealed tissue-specific regulatory elements which were associated with tissue-relevant biologi-cal functions.We identified both positive and negative significant correlations between the regulatory elements and gene transcripts,which showed distinct distributions in terms of their strength and distances from corresponding genes.We investigated the presence of transposable elements(TEs)in open chromatin regions across all tissues,these included identifications of porcine endogenous retroviruses(PERVs)exhibiting high accessibility in liver and homology of porcine specific virus sequences to universally accessible transposable elements.Furthermore,we prior-itized a potential causal variant for polyunsaturated fatty acid in the muscle.Conclusions:Our data provides a novel multi-tissues accessible chromatin landscape that serve as an important resource for interpreting regulatory sequences in tissue-specific and conserved biological functions,as well as regula-tory variants of loci associated with complex traits in pigs.
基金supported by the National Natural Science Foundation of China(82173773,82273893,82373829)the Natural Science Foundation of Guangdong Province,China(2021A0505030039,2021A0505020014)+1 种基金the High-End Foreign Experts Project,China(G2021199005L)the Science and Technology Program of Guangdong Provincial Medical Products Administration,China(2023TDZ11)。
文摘Due to low immobilized ligand density,limited binding capacity,and severe interference from serum proteins,developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge.In this study,mimotope peptide modified pompon mum-like biomimetic magnetic microparticles(MMPs,3.8μm)that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time.Benefit from the numerous ligand binding sites(Ni^(2+))on the pompon mum-like MMPs,these novel materials achieved≥10 times higher peptide ligand densities(>2300 mg/g)and antibody binding capacities(1380 mg/g)compared to previous reported biomaterials.Leveraging the high specificity of the mimotope peptide,rituximab can be precisely recognized and enriched from cell culture media or serum samples.We also established an LC-MS/MS method using the MMPs for tracking rituximab biotransformation in patient serum.Intriguingly,deamidation of Asn55 and Asn33,as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab,which could potentially influence antibody function and require careful monitoring.Overall,these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies,offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.
基金This work was supported by the National Key Research and Development Program of China(2021YFF1000601).
文摘Dear Editor,Mitochondria are the center of cellular energy generation and free radical metabolism,with important functions in regulating intracellular calcium levels,cell apoptosis,cell cycle and epigenetic modifications.Mitochondrial DNA copy number(mtDNA-CN)is an indicator of mitochondrial biogenesis and has been associated with several diseases,such as cardiovascular disease,depression,chronic kidney disease and aging in humans(Clyde,2022).
文摘Correction:aBIOTECH(2022)3:212–223 https://doi.org/10.1007/s42994-022-00082-5 The copyright holder for this article was incorrectly given as’Agricultural Information Institute,Chinese Academy of Agricultural Sciences’but should have been’The Authors’.This article was originally published with the incorrect licence;it should have been:Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons licence,unless indicated otherwise in a credit line to the material.
基金supported by Joint Innovation Fund for Regional Development of National Natural Science Foundation of China(No.U20A20134)Leading Talent of Technological Innovation of Ten-Thousands Talents Program of Zhejiang Province(No.2020R52012).
文摘Polyhalogenated carbazoles(PHCZs)have been widely accepted as emerging pollutants,whereas their ecological and health risks remain uncertain.Herein,female and male Sprague-Dawley(SD)mice were treated with four typical PHCZs to investigate their negative consequences,along with alternations in gutmicrobiota to indicate underlyingmechanisms.In female mice,the relative liver weight ratio increased after four PHCZs exposure;2-bromocarbazole(2-BCZ)increased urine glucose level;3-bromocarbazole(3-BCZ)decreased the glucose and total cholesterol levels;3,6-dichlorocarbazole(3,6-DCCZ)decreased glucose level.The only disturbed biochemical index in male mice was the promoted alkaline phosphatase(ALP)level by 3,6-DCCZ.We also found that the differential blood biochemical indices were correlated with gut microbiota.3-BCZ and 3,6-DCCZ altered Bacteroidetes and Proteobacteria phyla in female and male mice,which were correlated with metabolic disorders.Our findings demonstrated the correlation between PHCZs induced potential hepatotoxicity andmetabolic disordersmay be due to their dioxin-like potentials and endocrine disrupting activities,and the gender differences might result from their estrogenic activities.Overall,data presented here can help to evaluate the ecological and health risks of PHCZs and reveal the underlying mechanisms.
基金This work was supported by the National Natural Science Foundation of China(Nos.21802114 and 21802115)China Postdoctoral Science Foundation(No.2019M662794)+1 种基金Natural Science Foundation of Hunan Province(Nos.2017XK2048,2018JJ3501,and 2019JJ50601)Project of Education Department of Hunan Province(No.21B0141).
文摘Rational construction of high-efficiency electrocatalysts for oxygen evolution reaction(OER)is critical for renewable-energy technologies,but it is highly challenging to rationally regulate their surface structures to improve the OER performance.Herein,we proposed a“model-etching”strategy to investigate chemical etching of CO_(3)O_(4).The cubic CO_(3)O_(4)nanocrystals enclosed by well-defined facets are synthesized as model crystals,whose uniform surface structures allow us to study the etching mechanism at atomic level.Etching kinetics study together with DFT calculations discloses that{111}facets,the highly active facets for OER,serve as etch-stop facets in the etching reaction and H_(2)SO_(4)molecules play a special role in creating surface Co2^(+),the active center of OER.These results direct us to rationally optimize the surface structures of CO_(3)O_(4) to develop highly active OER electrocatalysts.The favorable performance of overpotential(η)and the Tafel slope decrease even to 268 mV@10 mA·cm−2 and 74 mV·dec−1,respectively.In general,our study shows that chemical etching of model crystals could help us rationally construct high-efficiency electrocatalysts.
基金supported by the National Natural Science Foundation of China (31790413, 31760657)。
文摘The limited knowledge of genomic noncoding and regulatory regions has restricted our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterized the spatiotemporal landscape of putative enhancers and promoters and their target genes by combining H3K27ac-targeted Ch IP-Seq and RNA-Seq in fetal(prenatal days 74–75) and adult(postnatal days 132–150) tissues(brain, liver, heart, muscle and small intestine) sampled from Asian aboriginal Bama Xiang and European highly selected Large White pigs of both sexes. We identified 101,290 H3K27ac peaks, marking 18,521promoters and 82,769 enhancers, including peaks that were active across all tissues and developmental stages(which could indicate safe harbor locus for exogenous gene insertion) and tissue-and developmental stage-specific peaks(which regulate gene pathways matching tissue-and developmental stage-specific physiological functions). We found that H3K27ac and DNA methylation in the promoter region of the XIST gene may be involved in X chromosome inactivation and demonstrated the utility of the present resource for revealing the regulatory patterns of known causal genes and prioritizing candidate causal variants for complex traits in pigs. In addition, we identified an average of 1,124 super-enhancers per sample and found that they were more likely to show tissue-specific activity than ordinary peaks. We have developed a web browser to improve the accessibility of the results(http://segtp.jxau.edu.cn/pencode/?genome=sus Scr11).
基金supported by the National Key R&D Program of China(2021YFA1102100 to J.X.)the National Natural Science Foundation of China(32070644)to J.X.,the Guangdong Basic and Applied Basic Research Foundation(2019A1515110387,2019B1515130004 to J.X.)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(No.22lgqb30 to JX).
文摘Assays for transposase-accessible chromatin through high-throughput sequencing(ATAC-seq)are effective tools in the study of genome-wide chromatin accessibility landscapes.With the rapid development of single-cell technology,open chromatin regions that play essential roles in epigenetic regulation have been measured at the single-cell level using single-cell ATAC-seq approaches.The application of scATAC-seq has become as popular as that of scRNA-seq.However,owing to the nature of scATAC-seq data,which are sparse and noisy,processing the data requires different methodologies and empirical experience.This review presents a practical guide for processing scATAC-seq data,from quality evaluation to downstream analysis,for various applications.In addition to the epigenomic profiling from scATAC-seq,we also discuss recent studies in which the function of non-coding variants has been investigated based on cell type-specific cis-regulatory elements and how to use the by-product genetic information obtained from scATAC-seq to infer single-cell copy number variants and trace cell lineage.We anticipate that this review will assist researchers in designing and implementing scATAC-seq assays to facilitate research in diverse fields.