Understanding genetic variant functionality is essential for advancing animal genomics and precision breeding.However,the lack of comprehensive functional genomic annotations in animals limits the effectiveness of mos...Understanding genetic variant functionality is essential for advancing animal genomics and precision breeding.However,the lack of comprehensive functional genomic annotations in animals limits the effectiveness of most variant function assessment methods.In this study,we gather 1030 raw epigenomic datasets from 10 animal species and systematically annotate 7 types of key regulatory regions,creating a comprehensive functional annotation map of animal genomic variants.Our findings demonstrate that integrating variants with regulatory annotations can identify tissues and cell types underlying economic traits,underscoring the utility of these annotations in functional variant discovery.Using our functional annotations,we rank the functional potential of genetic variants and classify over 127 million candidate variants into 5 functional confidence categories,with high-confidence variants significantly enriched in eQTLs and trait-associated SNPs.Incorporating these variants into genomic prediction models can improve estimated breeding value accuracy,demonstrating their practical utility in breeding programs.To facilitate the use of our results,we develop the Integrated Functional Mutation(IFmut:http://www.ifmutants.com:8212)platform,enabling researchers to explore regulatory annotations and assess the functional potential of animal variants efficiently.Our study provides a robust framework for functional genomic annotations in farm animals,enhancing variant function assessment and breeding precision.展开更多
Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the g...Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the gut barrier,and the evolution of core microbiota in the gut of calves of different ages.Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves.Disruption of the gut microbiome leads to digestive diseases in calves,such as diarrhea and intestinal inflammation.Microbiota already exists in the gut of calf fetuses,and the colonization of microbiota continues to change dynamically under the influence of various factors,which include probiotics,diet,age,and genotype.Colonization depends on the interaction between the gut microbiota and the immune system of calves.The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.展开更多
Cold stress in low-temperature environments can trigger changes in gene expression,but epigenomics regulation of temperature stability in vital tissues,including the fat and diencephalon,is still unclear.Here,we explo...Cold stress in low-temperature environments can trigger changes in gene expression,but epigenomics regulation of temperature stability in vital tissues,including the fat and diencephalon,is still unclear.Here,we explore the cold-induced changes in epigenomic features in the diencephalon and fat tissues of two cold-resistant Chinese pig breeds,Min and Enshi black(ES)pigs,utilizing H3K27ac CUT&Tag,RNA-seq,and selective signature analysis.Our results show significant alterations in H3K27ac modifications in the diencephalon of Min pigs and the fat of ES pigs after cold exposure.Dramatic changes in H3K27ac modifications in the diencephalon of Min pig are primarily associated with genes involved in energy metabolism and hormone regulation,whereas those in the fat of ES pig are primarily associated with immunity-related genes.Moreover,transcription factors PRDM1 and HSF1,which show evidence of selection,are enriched in genomic regions presenting cold-responsive alterations in H3K27ac modification in the Min pig diencephalon and ES pig fat,respectively.Our results indicate the diversity of epigenomic response mechanisms to cold exposure between Min and ES pigs,providing unique epigenetic resources for studies of low-temperature adaptation in large mammals.展开更多
Compared to intravenous injection,oral administration is attractive due to its many advantages for cancer therapy.Taken physiological barriers and other profiles of oral anticancer drug carriers into consideration,tar...Compared to intravenous injection,oral administration is attractive due to its many advantages for cancer therapy.Taken physiological barriers and other profiles of oral anticancer drug carriers into consideration,targeted and pH-sensitive polyzwitterionic liposomes(ZL)based on zwitterionic poly(carboxybetaine)(PCB)were constructed for oral delivery of doxorubicin hydrochloride(DOX·HCl)for cancer therapy.The DOX-ZL with 40%trehalose had good lyophilization stability,which would be packaged into enteric capsules to enhance their stability in stomach.In addition,DOX-ZL exhibited good storage stability and serum stability.The DOX-ZL could achieve controlled release of DOX·HCl at the endosomal pH 5.0 due to the pH-sensitive of zwitterionic PCB.Importantly,DOX-ZL could targeted deliver DOX·HCl to Caco-2 cells to cross the intestinal epithelial cell layer.The empty ZL had good biocompatibility,while DOX-ZL significantly inhibited tumor cells growth due to their high cellular uptake and controlled drug release ability.Therefore,this work provided a promising approach for oral cancer therapy.展开更多
Power sharing can improve the benefit of the multi-microgrid(MMG)system.However,the information disclosure may appear during the sharing process,which would bring privacy risk to a local microgrid.Actually,the risk an...Power sharing can improve the benefit of the multi-microgrid(MMG)system.However,the information disclosure may appear during the sharing process,which would bring privacy risk to a local microgrid.Actually,the risk and coordination cost are different in different sharing modes.Therefore,this paper develops a decision-making method to decide the most suitable one of three mostly used sharing modes(i.e.,cooperative game with complete information,cooperative game with incomplete information,and noncooperative game).Firstly,power sharing paradigms and coordination mechanisms in the three modes are formulated in detail.Particularly,different economic operation models of MMG system are included to analyze the economic benefit from different sharing modes.Based on the different disclosed information,the risk cost is evaluated by using the simplified fuzzy analytic hierarchy process(FAHP).And the coordination cost for different sharing modes is expressed in different functions.In addition,a hierarchical evaluation system including three decision-making factors(e.g.,economics,risk,and coordination)is set up.Meanwhile,a combination weighting method(e.g.,the simplified FAHP combined with the anti-entropy weight method)is applied to obtain the weight of each factor for comprehensive evaluation.Finally,the optimal sharing solution of MMG system is decided by comparing and analyzing the difference among the three sharing modes.Numerical results validate that the proposed method can provide a reference to deciding a suitable sharing mode.展开更多
基金supported by the National Natural Science Foundation of China(32341051)the grant from Department of Agriculture and Rural Affairs of Hubei Province(HBZY2023B006-02)+2 种基金the National Funding(2023ZD04050)the National Natural Science Foundation of China Outstanding Youth(32125035)the National Key R&D Young Scientists Project(2022YFD1302000).
文摘Understanding genetic variant functionality is essential for advancing animal genomics and precision breeding.However,the lack of comprehensive functional genomic annotations in animals limits the effectiveness of most variant function assessment methods.In this study,we gather 1030 raw epigenomic datasets from 10 animal species and systematically annotate 7 types of key regulatory regions,creating a comprehensive functional annotation map of animal genomic variants.Our findings demonstrate that integrating variants with regulatory annotations can identify tissues and cell types underlying economic traits,underscoring the utility of these annotations in functional variant discovery.Using our functional annotations,we rank the functional potential of genetic variants and classify over 127 million candidate variants into 5 functional confidence categories,with high-confidence variants significantly enriched in eQTLs and trait-associated SNPs.Incorporating these variants into genomic prediction models can improve estimated breeding value accuracy,demonstrating their practical utility in breeding programs.To facilitate the use of our results,we develop the Integrated Functional Mutation(IFmut:http://www.ifmutants.com:8212)platform,enabling researchers to explore regulatory annotations and assess the functional potential of animal variants efficiently.Our study provides a robust framework for functional genomic annotations in farm animals,enhancing variant function assessment and breeding precision.
基金funded by the grants from the National Key R&D Program of China(No.2022YFD1301004)National Natural Science Foundation of China(No.31601962)+1 种基金Fundamental Research Funds for the Central Universities(2662019QD021)Key Laboratory of Molecular Animal Nutrition of Zhejiang University(KLMAN202101 and KLMAN202205)。
文摘Colonization and development of the gut microbiome are crucial for the growth and health of calves.In this review,we summarized the colonization,beneficial nutrition,immune function of gut microbiota,function of the gut barrier,and the evolution of core microbiota in the gut of calves of different ages.Homeostasis of gut microbiome is beneficial for nutritional and immune system development of calves.Disruption of the gut microbiome leads to digestive diseases in calves,such as diarrhea and intestinal inflammation.Microbiota already exists in the gut of calf fetuses,and the colonization of microbiota continues to change dynamically under the influence of various factors,which include probiotics,diet,age,and genotype.Colonization depends on the interaction between the gut microbiota and the immune system of calves.The abundance and diversity of these commensal microbiota stabilize and play a critical role in the health of calves.
基金supported by the National Natural Science Foundation of China(32202634)National Natural Science Foundation of China(31961143020)+2 种基金National Natural Science Foundation of China(U20A2052)China Agricultural Research System(CARS-35)the Heilongjiang Provincial Research Institutes Research Business Fund Project(CZKYF2023-1-B009)。
文摘Cold stress in low-temperature environments can trigger changes in gene expression,but epigenomics regulation of temperature stability in vital tissues,including the fat and diencephalon,is still unclear.Here,we explore the cold-induced changes in epigenomic features in the diencephalon and fat tissues of two cold-resistant Chinese pig breeds,Min and Enshi black(ES)pigs,utilizing H3K27ac CUT&Tag,RNA-seq,and selective signature analysis.Our results show significant alterations in H3K27ac modifications in the diencephalon of Min pigs and the fat of ES pigs after cold exposure.Dramatic changes in H3K27ac modifications in the diencephalon of Min pig are primarily associated with genes involved in energy metabolism and hormone regulation,whereas those in the fat of ES pig are primarily associated with immunity-related genes.Moreover,transcription factors PRDM1 and HSF1,which show evidence of selection,are enriched in genomic regions presenting cold-responsive alterations in H3K27ac modification in the Min pig diencephalon and ES pig fat,respectively.Our results indicate the diversity of epigenomic response mechanisms to cold exposure between Min and ES pigs,providing unique epigenetic resources for studies of low-temperature adaptation in large mammals.
基金financially supported by the Fundamental Research Funds for the Central Universities(grant No.06500230,FRF-BR-23-02B)the National Natural Science Foundation of China(grant No.32071391)+1 种基金the Interdisciplinary Research Project for Young Teachers of USTB(Fundamental Research Funds for the Central Universities,FRF-IDRY-23-019)the Beijing Nova Program(grant No.20230484423).
文摘Compared to intravenous injection,oral administration is attractive due to its many advantages for cancer therapy.Taken physiological barriers and other profiles of oral anticancer drug carriers into consideration,targeted and pH-sensitive polyzwitterionic liposomes(ZL)based on zwitterionic poly(carboxybetaine)(PCB)were constructed for oral delivery of doxorubicin hydrochloride(DOX·HCl)for cancer therapy.The DOX-ZL with 40%trehalose had good lyophilization stability,which would be packaged into enteric capsules to enhance their stability in stomach.In addition,DOX-ZL exhibited good storage stability and serum stability.The DOX-ZL could achieve controlled release of DOX·HCl at the endosomal pH 5.0 due to the pH-sensitive of zwitterionic PCB.Importantly,DOX-ZL could targeted deliver DOX·HCl to Caco-2 cells to cross the intestinal epithelial cell layer.The empty ZL had good biocompatibility,while DOX-ZL significantly inhibited tumor cells growth due to their high cellular uptake and controlled drug release ability.Therefore,this work provided a promising approach for oral cancer therapy.
基金supported by the National Key R&D Program of China(No.2019YFE0123600)the National Natural Science Foundation of China(No.52077146)the Sichuan Science and Technology Program(Grant No.2021YFSY0052).
文摘Power sharing can improve the benefit of the multi-microgrid(MMG)system.However,the information disclosure may appear during the sharing process,which would bring privacy risk to a local microgrid.Actually,the risk and coordination cost are different in different sharing modes.Therefore,this paper develops a decision-making method to decide the most suitable one of three mostly used sharing modes(i.e.,cooperative game with complete information,cooperative game with incomplete information,and noncooperative game).Firstly,power sharing paradigms and coordination mechanisms in the three modes are formulated in detail.Particularly,different economic operation models of MMG system are included to analyze the economic benefit from different sharing modes.Based on the different disclosed information,the risk cost is evaluated by using the simplified fuzzy analytic hierarchy process(FAHP).And the coordination cost for different sharing modes is expressed in different functions.In addition,a hierarchical evaluation system including three decision-making factors(e.g.,economics,risk,and coordination)is set up.Meanwhile,a combination weighting method(e.g.,the simplified FAHP combined with the anti-entropy weight method)is applied to obtain the weight of each factor for comprehensive evaluation.Finally,the optimal sharing solution of MMG system is decided by comparing and analyzing the difference among the three sharing modes.Numerical results validate that the proposed method can provide a reference to deciding a suitable sharing mode.