Background Domestic goose breeds are descended from either the Swan goose(Anser cygnoides)or the Greylag goose(Anser anser),exhibiting variations in body size,reproductive performance,egg production,feather color,and ...Background Domestic goose breeds are descended from either the Swan goose(Anser cygnoides)or the Greylag goose(Anser anser),exhibiting variations in body size,reproductive performance,egg production,feather color,and other phenotypic traits.Constructing a pan-genome facilitates a thorough identification of genetic variations,thereby deepening our comprehension of the molecular mechanisms underlying genetic diversity and phenotypic variability.Results To comprehensively facilitate population genomic and pan-genomic analyses in geese,we embarked on the task of 659 geese whole genome resequencing data and compiling a database of 155 RNA-seq samples.By constructing the pan-genome for geese,we generated non-reference contigs totaling 612 Mb,unveiling a collection of 2,813 novel genes and pinpointing 15,567 core genes,1,324 softcore genes,2,734 shell genes,and 878 cloud genes in goose genomes.Furthermore,we detected an 81.97 Mb genomic region showing signs of genome selection,encompassing the TGFBR2 gene correlated with variations in body weight among geese.Genome-wide association studies utilizing single nucleotide polymorphisms(SNPs)and presence-absence variation revealed significant genomic associations with various goose meat quality,reproductive,and body composition traits.For instance,a gene encoding the SVEP1 protein was linked to carcass oblique length,and a distinct gene-CDS haplotype of the SVEP1 gene exhibited an association with carcass oblique length.Notably,the pan-genome analysis revealed enrichment of variable genes in the“hair follicle maturation”Gene Ontology term,potentially linked to the selection of feather-related traits in geese.A gene presence-absence variation analysis suggested a reduced frequency of genes associated with“regulation of heart contraction”in domesticated geese compared to their wild counterparts.Our study provided novel insights into gene expression features and functions by integrating gene expression patterns across multiple organs and tissues in geese and analyzing population variation.Conclusion This accomplishment originates from the discernment of a multitude of selection signals and candidate genes associated with a wide array of traits,thereby markedly enhancing our understanding of the processes underlying domestication and breeding in geese.Moreover,assembling the pan-genome for geese has yielded a comprehensive apprehension of the goose genome,establishing it as an indispensable asset poised to offer innovative viewpoints and make substantial contributions to future geese breeding initiatives.展开更多
Background Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant ener...Background Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant energy intake. As a result, goose offers an excellent model for studying obesity, metabolic disorders, and liver diseases in mammals. Although the impact of the three-dimensional arrangement of chromatin within the cell nucleus on gene expression and transcriptional regulation is widely acknowledged, the precise functions of chromatin architecture reorganization during fat deposition in goose liver tissues still need to be fully comprehended.Results In this study, geese exhibited more pronounced changes in the liver index and triglyceride(TG) content following the consumption of the high-fat diet(HFD) than mice without significant signs of inflammation. Additionally, we performed comprehensive analyses on 10 goose liver tissues(5 HFD, 5 normal), including generating highresolution maps of chromatin architecture, conducting whole-genome gene expression profiling, and identifying H3K27ac peaks in the livers of geese and mice subjected to the HFD. Our results unveiled a multiscale restructuring of chromatin architecture, encompassing Compartment A/B, topologically associated domains, and interactions between promoters and enhancers. The dynamism of the three-dimensional genome architecture, prompted by the HFD, assumed a pivotal role in the transcriptional regulation of crucial genes. Furthermore, we identified genes that regulate chromatin conformation changes, contributing to the metabolic adaptation process of lipid deposition and hepatic fat changes in geese in response to excessive energy intake. Moreover, we conducted a cross-species analysis comparing geese and mice exposed to the HFD, revealing unique characteristics specific to the goose liver compared to a mouse. These chromatin conformation changes help elucidate the observed characteristics of fat deposition and hepatic fat regulation in geese under conditions of excessive energy intake.Conclusions We examined the dynamic modifications in three-dimensional chromatin architecture and gene expression induced by an HFD in goose liver tissues. We conducted a cross-species analysis comparing that of mice. Our results contribute significant insights into the chromatin architecture of goose liver tissues, offering a novel perspective for investigating mammal liver diseases.展开更多
Colorectal cancer(CRC)is among the leading causes of cancer mortality.The lifetime risk of developing CRC is about 5%in adult males and females.CRC is usually diagnosed at an advanced stage,and at this point therapy h...Colorectal cancer(CRC)is among the leading causes of cancer mortality.The lifetime risk of developing CRC is about 5%in adult males and females.CRC is usually diagnosed at an advanced stage,and at this point therapy has a limited impact on cure rates and long-term survival.Novel and/or improved CRC therapeutic options are needed.The involvement of microRNAs(miRNAs)in cancer development has been reported,and their regulation in many oncogenic pathways suggests their potent tumor suppressor action.Although miRNAs provide a promising therapeutic approach for cancer,challenges such as biodegradation,specificity,stability and toxicity,impede their progression into clinical trials.Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy.The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.展开更多
Poly-β-(1,6)-N-acetylglucosamine (PNAG), the chief mediator of intercellular adhesion in many bacteria, plays an important role in biofilm formation. The pgaABCD locus was recognized from the whole genome sequence of...Poly-β-(1,6)-N-acetylglucosamine (PNAG), the chief mediator of intercellular adhesion in many bacteria, plays an important role in biofilm formation. The pgaABCD locus was recognized from the whole genome sequence of A. junii SH205. The enzyme glycosyltransferase, PgaC, catalyzes the production of PNAG with N-acetyl-D-glucosamine monomer. In this study, the possibility of PNAG biosynthesis in A. junii SH205 with its own PgaC was explored with the aid of bioinformatics. Multiple alignments of PgaC sequences of different bacteria were used to identify conserved amino acid residues that might be critical for the functioning of the protein. Three-dimensional model of A. junii SH205 PgaC was generated for spatial visualization of amino acid residues. The analyses have shown that the protein PgaC has five conserved amino acids, Asp<sup>140</sup>, Asp<sup>233</sup>, Gln<sup>269</sup>, Arg<sup>272</sup> and Trp<sup>273</sup>, critical for the activity of enzyme. Interaction of UDP-N-acetylglucosamine within the conserved pocket of glycosyltransferase was explored from molecular docking studies.展开更多
Diabetic retinopathy(DR)affects approximately one-third of diabetic patients and,if left untreated,progresses to proliferative DR(PDR)with associated vitreous hemorrhage,retinal detachment,iris neovascularization,glau...Diabetic retinopathy(DR)affects approximately one-third of diabetic patients and,if left untreated,progresses to proliferative DR(PDR)with associated vitreous hemorrhage,retinal detachment,iris neovascularization,glaucoma and irreversible blindness.In vitreous samples of human patients with PDR,we found elevated levels of hypoxia inducible factor 1 alpha(HIF1α).HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases.To recreate the human PDR phenotype for a preclinical animal model,we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein,a protein that targets HIF1αfor ubiquitination.We found that the neuroretinal cells in these mice overexpressed HIF1αand developed severe,irreversible ischemic retinopathy that has features of human PDR.Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders.In addition,this model system can be used to manipulate the modulation of the hypoxia signaling pathways,for the treatment of non-ocular ischemic and inflammatory disorders.展开更多
Apples are rich sources of bioactive compounds(e.g.,anthocyanins,flavanols,flavonols,and antioxidant activity),and micronutrients(e.g.,vitamins,zinc,and iron)that are essential for normal human body functions.These co...Apples are rich sources of bioactive compounds(e.g.,anthocyanins,flavanols,flavonols,and antioxidant activity),and micronutrients(e.g.,vitamins,zinc,and iron)that are essential for normal human body functions.These compounds in apples help to regulate immune responses and protect against chronic diseases by neutralizing and eliminating cellular free radicals.Apple fruit production is ranked second globally,which has economic implication.The conventional industry practice of using chlorine-based chemical disinfectants has been discouraged based on public health concerns,and by strict policies limiting chemical residues on fresh or minimally processed ready to eat fruit.Therefore,the aim of this review is to provide a critical assessment on the status of emerging non-thermal technologies such as cold plasma,pulsed electric fields,ozone,electrolyzed water,and edible coatings for the whole and minimally processed apple fruit industry.The influence of these non-thermal technologies on microbial decontamination,preservation of bioactive compounds,and overall quality of apples during storage is discussed.In addition,based on extensive report on various studies about non-thermal technologies for apples.This review concluded that future investigations should focus on balancing the decontamination performance of these non-thermal technologies with the preservation of essential nutritional quality attributes,providing guidance for the apple fruit industry.展开更多
基金funding from several sources,including the Chongqing Scientific Research Institution Performance Incentive Project(grant number cstc2022jxjl80007)the Earmarked Fund for China Agriculture Research System(grant number CARS-42-51)+5 种基金the Chongqing Scientific Research Institution Performance Incentive Project(grant number 22527 J)the Key R&D Project in Agriculture and Animal Husbandry of Rongchang(grant number No.22534C-22)Natural Science Foundation of Chongqing Project,grant number CSTB2022NSCQ-MSX0434Natural Science Foundation of Sichuan Project,grant number 2022NSFSC0605Natural Science Foundation of Sichuan Project,grant number 2021YFS0379the Chongqing Technology Innovation and Application Development Project(grant number No.cstc2021ycjh-bgzxm0248)。
文摘Background Domestic goose breeds are descended from either the Swan goose(Anser cygnoides)or the Greylag goose(Anser anser),exhibiting variations in body size,reproductive performance,egg production,feather color,and other phenotypic traits.Constructing a pan-genome facilitates a thorough identification of genetic variations,thereby deepening our comprehension of the molecular mechanisms underlying genetic diversity and phenotypic variability.Results To comprehensively facilitate population genomic and pan-genomic analyses in geese,we embarked on the task of 659 geese whole genome resequencing data and compiling a database of 155 RNA-seq samples.By constructing the pan-genome for geese,we generated non-reference contigs totaling 612 Mb,unveiling a collection of 2,813 novel genes and pinpointing 15,567 core genes,1,324 softcore genes,2,734 shell genes,and 878 cloud genes in goose genomes.Furthermore,we detected an 81.97 Mb genomic region showing signs of genome selection,encompassing the TGFBR2 gene correlated with variations in body weight among geese.Genome-wide association studies utilizing single nucleotide polymorphisms(SNPs)and presence-absence variation revealed significant genomic associations with various goose meat quality,reproductive,and body composition traits.For instance,a gene encoding the SVEP1 protein was linked to carcass oblique length,and a distinct gene-CDS haplotype of the SVEP1 gene exhibited an association with carcass oblique length.Notably,the pan-genome analysis revealed enrichment of variable genes in the“hair follicle maturation”Gene Ontology term,potentially linked to the selection of feather-related traits in geese.A gene presence-absence variation analysis suggested a reduced frequency of genes associated with“regulation of heart contraction”in domesticated geese compared to their wild counterparts.Our study provided novel insights into gene expression features and functions by integrating gene expression patterns across multiple organs and tissues in geese and analyzing population variation.Conclusion This accomplishment originates from the discernment of a multitude of selection signals and candidate genes associated with a wide array of traits,thereby markedly enhancing our understanding of the processes underlying domestication and breeding in geese.Moreover,assembling the pan-genome for geese has yielded a comprehensive apprehension of the goose genome,establishing it as an indispensable asset poised to offer innovative viewpoints and make substantial contributions to future geese breeding initiatives.
基金supported by the National Key R&D Program of China (2022YFF1000100 to Long Jin and 2023YFD1300012 to Long Jin)the Sichuan Science and Technology Program (2022JDJQ0054 to Long Jin and 2021YFYZ0009 to Mingzhou Li)the National Natural Science Foundation of China (32225046 to Mingzhou Li)。
文摘Background Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant energy intake. As a result, goose offers an excellent model for studying obesity, metabolic disorders, and liver diseases in mammals. Although the impact of the three-dimensional arrangement of chromatin within the cell nucleus on gene expression and transcriptional regulation is widely acknowledged, the precise functions of chromatin architecture reorganization during fat deposition in goose liver tissues still need to be fully comprehended.Results In this study, geese exhibited more pronounced changes in the liver index and triglyceride(TG) content following the consumption of the high-fat diet(HFD) than mice without significant signs of inflammation. Additionally, we performed comprehensive analyses on 10 goose liver tissues(5 HFD, 5 normal), including generating highresolution maps of chromatin architecture, conducting whole-genome gene expression profiling, and identifying H3K27ac peaks in the livers of geese and mice subjected to the HFD. Our results unveiled a multiscale restructuring of chromatin architecture, encompassing Compartment A/B, topologically associated domains, and interactions between promoters and enhancers. The dynamism of the three-dimensional genome architecture, prompted by the HFD, assumed a pivotal role in the transcriptional regulation of crucial genes. Furthermore, we identified genes that regulate chromatin conformation changes, contributing to the metabolic adaptation process of lipid deposition and hepatic fat changes in geese in response to excessive energy intake. Moreover, we conducted a cross-species analysis comparing geese and mice exposed to the HFD, revealing unique characteristics specific to the goose liver compared to a mouse. These chromatin conformation changes help elucidate the observed characteristics of fat deposition and hepatic fat regulation in geese under conditions of excessive energy intake.Conclusions We examined the dynamic modifications in three-dimensional chromatin architecture and gene expression induced by an HFD in goose liver tissues. We conducted a cross-species analysis comparing that of mice. Our results contribute significant insights into the chromatin architecture of goose liver tissues, offering a novel perspective for investigating mammal liver diseases.
基金funded by the Department of Science and Innovation/Mintek Nanotechnology Innovation Centre.
文摘Colorectal cancer(CRC)is among the leading causes of cancer mortality.The lifetime risk of developing CRC is about 5%in adult males and females.CRC is usually diagnosed at an advanced stage,and at this point therapy has a limited impact on cure rates and long-term survival.Novel and/or improved CRC therapeutic options are needed.The involvement of microRNAs(miRNAs)in cancer development has been reported,and their regulation in many oncogenic pathways suggests their potent tumor suppressor action.Although miRNAs provide a promising therapeutic approach for cancer,challenges such as biodegradation,specificity,stability and toxicity,impede their progression into clinical trials.Nanotechnology strategies offer diverse advantages for the use of miRNAs for CRC-targeted delivery and therapy.The merits of using nanocarriers for targeted delivery of miRNA-formulations are presented herein to highlight the role they can play in miRNA-based CRC therapy by targeting different stages of the disease.
文摘Poly-β-(1,6)-N-acetylglucosamine (PNAG), the chief mediator of intercellular adhesion in many bacteria, plays an important role in biofilm formation. The pgaABCD locus was recognized from the whole genome sequence of A. junii SH205. The enzyme glycosyltransferase, PgaC, catalyzes the production of PNAG with N-acetyl-D-glucosamine monomer. In this study, the possibility of PNAG biosynthesis in A. junii SH205 with its own PgaC was explored with the aid of bioinformatics. Multiple alignments of PgaC sequences of different bacteria were used to identify conserved amino acid residues that might be critical for the functioning of the protein. Three-dimensional model of A. junii SH205 PgaC was generated for spatial visualization of amino acid residues. The analyses have shown that the protein PgaC has five conserved amino acids, Asp<sup>140</sup>, Asp<sup>233</sup>, Gln<sup>269</sup>, Arg<sup>272</sup> and Trp<sup>273</sup>, critical for the activity of enzyme. Interaction of UDP-N-acetylglucosamine within the conserved pocket of glycosyltransferase was explored from molecular docking studies.
基金This work was supported by the National Institute of Health Core(5P30EY019007)National Cancer Institute Core(5P30CA013696)and unrestricted funds from Research to Prevent Blindness+6 种基金New York,NY,USA.KJW was supported by the National Institute of Health(5T32EY013933 and 5T32DK007647-20)during these experiments and is currently supported by the National Cancer Institute(F32CA196065)SHT is a member of the RD-CURE Consortium and is supported by the Tistou and Charlotte Kerstan Foundation,the National Institute of Health(R01EY018213)the Research to Prevent Blindness Physician-Scientist Award,Association for Research in Vision and Ophthalmology Foundation,Macula Society,the Barbara and Donald Jonas Family Fund,the Schneeweiss Stem Cell Fund,New York State(C029572)the Foundation Fighting Blindness New York Regional Research Center Grant(C-NY05-0705-0312)the Joel Hoffman Fund,the Professor Gertrude Rothschild Stem Cell Foundation,and the Gebroe Family FoundationVBM is supported by NIH Grants K08EY020530,R01EY016822 and Research to Prevent Blindness,New York,NY,USAMBG is supported by R01EY07739,R01EY012601,R01HL110170 and R01DK090730.
文摘Diabetic retinopathy(DR)affects approximately one-third of diabetic patients and,if left untreated,progresses to proliferative DR(PDR)with associated vitreous hemorrhage,retinal detachment,iris neovascularization,glaucoma and irreversible blindness.In vitreous samples of human patients with PDR,we found elevated levels of hypoxia inducible factor 1 alpha(HIF1α).HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases.To recreate the human PDR phenotype for a preclinical animal model,we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein,a protein that targets HIF1αfor ubiquitination.We found that the neuroretinal cells in these mice overexpressed HIF1αand developed severe,irreversible ischemic retinopathy that has features of human PDR.Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders.In addition,this model system can be used to manipulate the modulation of the hypoxia signaling pathways,for the treatment of non-ocular ischemic and inflammatory disorders.
基金research supported by the National Research Foundation(NRF)of South Africa(Grant Nos.137990 and 146360)awarded to Dr OJ CalebThe HORTGRO science project(Grant No.NF8-2021)awarded to Dr ZA Belay is also gratefully acknowledged.
文摘Apples are rich sources of bioactive compounds(e.g.,anthocyanins,flavanols,flavonols,and antioxidant activity),and micronutrients(e.g.,vitamins,zinc,and iron)that are essential for normal human body functions.These compounds in apples help to regulate immune responses and protect against chronic diseases by neutralizing and eliminating cellular free radicals.Apple fruit production is ranked second globally,which has economic implication.The conventional industry practice of using chlorine-based chemical disinfectants has been discouraged based on public health concerns,and by strict policies limiting chemical residues on fresh or minimally processed ready to eat fruit.Therefore,the aim of this review is to provide a critical assessment on the status of emerging non-thermal technologies such as cold plasma,pulsed electric fields,ozone,electrolyzed water,and edible coatings for the whole and minimally processed apple fruit industry.The influence of these non-thermal technologies on microbial decontamination,preservation of bioactive compounds,and overall quality of apples during storage is discussed.In addition,based on extensive report on various studies about non-thermal technologies for apples.This review concluded that future investigations should focus on balancing the decontamination performance of these non-thermal technologies with the preservation of essential nutritional quality attributes,providing guidance for the apple fruit industry.
