Based upon motion capture,a semi-automatic technique for fast facial animation was implemented. While capturing the facial expressions from a performer,a camera was used to record her /his front face as a texture map....Based upon motion capture,a semi-automatic technique for fast facial animation was implemented. While capturing the facial expressions from a performer,a camera was used to record her /his front face as a texture map. The radial basis function( RBF) technique was utilized to deform a generic facial model and the texture was remapped to generate a personalized face.Partitioning the personalized face into three regions and using the captured facial expression data,the RBF and Laplacian operator,and mean-value coordinates were implemented to deform each region respectively. With shape blending,the three regions were combined together to construct the final face model. Our results show that the technique is efficient in generating realistic facial animation.展开更多
Why it needs to take the initiative in the shape in the painting？ Refine images of the shape of the objective initiatively, not only can enhance the artistic appeal and creators emotions, can also highlight the aesth...Why it needs to take the initiative in the shape in the painting？ Refine images of the shape of the objective initiatively, not only can enhance the artistic appeal and creators emotions, can also highlight the aesthetic orientation creators to make their paintings to impress the audience and resonate, so works of art have a higher aesthetic value. Similarly, in the entire animation movie, animation character modeling also has an important position, and a good cartoon must have a good role model to fully convey the story and character. This article attempts to analyze the shape of the image of the Disney animated start, make deep analysis on necessity of initiative modeling in the art of painting and development of initiative modeling, to enhance the performance of artists and diverse personality development, which is a requirement of modem art, but also the law of development of the arts.展开更多
Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,wi...Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.展开更多
Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is...Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.展开更多
The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays a...The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.展开更多
Background There is a growing focus on using various plant-derived agricultural by-products to increase the benefits of pig farming,but these feedstuffs are fibrous in nature.This study investigated the relationship b...Background There is a growing focus on using various plant-derived agricultural by-products to increase the benefits of pig farming,but these feedstuffs are fibrous in nature.This study investigated the relationship between dietary fiber physicochemical properties and feedstuff fermentation characteristics and their effects on nutrient utilization,energy metabolism,and gut microbiota in growing pigs.Methods Thirty-six growing barrows(47.2±1.5 kg)were randomly allotted to 6 dietary treatments with 2 apparent viscosity levels and 3β-glucan-to-arabinoxylan ratios.In the experiment,nutrient utilization,energy metabolism,fecal microbial community,and production and absorption of short-chain fatty acid(SCFA)of pigs were investigated.In vitro digestion and fermentation models were used to compare the fermentation characteristics of feedstuffs and ileal digesta in the pig’s hindgut.Results The production dynamics of SCFA and dry matter corrected gas production of different feedstuffs during in vitro fermentation were different and closely related to the physical properties and chemical structure of the fiber.In animal experiments,increasing the dietary apparent viscosity and theβ-glucan-to-arabinoxylan ratios both increased the apparent ileal digestibility(AID),apparent total tract digestibility(ATTD),and hindgut digestibility of fiber components while decreasing the AID and ATTD of dry matter and organic matter(P<0.05).In addition,increasing dietary apparent viscosity andβ-glucan-to-arabinoxylan ratios both increased gas exchange,heat production,and protein oxidation,and decreased energy deposition(P<0.05).The dietary apparent viscosity andβ-glucanto-arabinoxylan ratios had linear interaction effects on the digestible energy,metabolizable energy,retained energy(RE),and net energy(NE)of the diets(P<0.05).At the same time,the increase of dietary apparent viscosity andβ-glucan-to-arabinoxylan ratios both increased SCFA production and absorption(P<0.05).Increasing the dietary apparent viscosity andβ-glucan-to-arabinoxylan ratios increased the diversity and abundance of bacteria(P<0.05)and the relative abundance of beneficial bacteria.Furthermore,increasing the dietaryβ-glucan-to-arabinoxylan ratios led to a linear increase in SCFA production during the in vitro fermentation of ileal digesta(P<0.001).Finally,the prediction equations for RE and NE were established.Conclusion Dietary fiber physicochemical properties alter dietary fermentation patterns and regulate nutrient utilization,energy metabolism,and pig gut microbiota composition and metabolites.展开更多
Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,ma...Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,making it a potentially superior feed additive.However,the efficacy,mechanistic differences,and comparative impacts of CA and CGA on fatty liver disease in laying hens remain unclear.This study aimed to evaluate and compare the effects of CA and CGA on production performance,egg quality,and fatty liver disease in laying hens.Results A total of 1,44061-week-old Hyline Brown laying hens were randomly divided into 8 groups and fed diets supplemented with basal diet,25,50,100 and 200 mg/kg of CA,and 100,200 and 400 mg/kg of CGA(CON,CA25,CA50,CA100,CA200,CGA100,CGA200 and CGA400,respectively)for 12 weeks.Both CA and CGA improved production performance and egg quality,while reducing markers of hepatic damage and lipid accumulation.CA and CGA significantly decreased TG,TC,and LDL-C levels and increased T-SOD activity.Transcriptomic and proteomic analyses revealed that CA and CGA reduced hepatic lipid accumulation through downregulation of lipid biosynthesis-related genes(ACLY,ACACA,FASN,and SCD1)and enhanced lipid transport and oxidation genes(FABPs,CD36,CPT1A,ACOX1,and SCP2).Of note,low-dose CA25 exhibited equivalent efficacy to the higher dose CGA100 group in alleviating fatty liver conditions.Mechanistically,CA and CGA alleviated lipid accumulation via activation of the ADPN-AMPK-PPARαsignaling pathway.Conclusions This study demonstrates that dietary CA and CGA effectively improve laying performance,egg quality,and hepatic lipid metabolism in laying hens,with CA potentially being more economical and efficient.Transcriptomic and proteomic evidence highlight shared mechanisms between CA25 and CGA100.These findings provide a foundation for CA and CGA as therapeutic agents for fatty liver disease and related metabolic diseases in hens,and also offer insights into the targeted modification of CGA(including the isomer of CGA)into CA,thereby providing novel strategies for the efficient utilization of CGA.Highlights(1)Dietary CA and CGA improve fatty liver,laying performance and egg quality.(2)Lower dose of CA25 achieves the equivalent improvement as CGA100 or CGA200.(3)CA and CGA mediate the ADPN-AMPK-PPARαpathway to alleviate fatty liver.展开更多
Background India harbors the world’s largest cattle population,encompassing over 50 distinct Bos indicus breeds.This rich genetic diversity underscores the inadequacy of a single reference genome to fully capture the...Background India harbors the world’s largest cattle population,encompassing over 50 distinct Bos indicus breeds.This rich genetic diversity underscores the inadequacy of a single reference genome to fully capture the genomic landscape of Indian cattle.To comprehensively characterize the genomic variation within Bos indicus and,specifically,dairy breeds,we aim to identify non-reference sequences and construct a comprehensive pangenome.Results Five representative genomes of prominent dairy breeds,including Gir,Kankrej,Tharparkar,Sahiwal,and Red Sindhi,were sequenced using 10X Genomics‘linked-read’technology.Assemblies generated from these linked-reads ranged from 2.70 Gb to 2.77 Gb,comparable to the Bos indicus Brahman reference genome.A pangenome of Bos indicus cattle was constructed by comparing the newly assembled genomes with the reference using alignment and graph-based methods,revealing 8 Mb and 17.7 Mb of novel sequence respectively.A confident set of 6,844 Non-reference Unique Insertions(NUIs)spanning 7.57 Mb was identified through both methods,representing the pange-nome of Indian Bos indicus breeds.Comparative analysis with previously published pangenomes unveiled 2.8 Mb(37%)commonality with the Chinese indicine pangenome and only 1%commonality with the Bos taurus pange-nome.Among these,2,312 NUIs encompassing~2 Mb,were commonly found in 98 samples of the 5 breeds and des-ignated as Bos indicus Common Insertions(BICIs)in the population.Furthermore,926 BICIs were identified within 682 protein-coding genes,54 long non-coding RNAs(lncRNA),and 18 pseudogenes.These protein-coding genes were enriched for functions such as chemical synaptic transmission,cell junction organization,cell-cell adhesion,and cell morphogenesis.The protein-coding genes were found in various prominent quantitative trait locus(QTL)regions,suggesting potential roles of BICIs in traits related to milk production,reproduction,exterior,health,meat,and carcass.Notably,63.21%of the bases within the BICIs call set contained interspersed repeats,predominantly Long Inter-spersed Nuclear Elements(LINEs).Additionally,70.28%of BICIs are shared with other domesticated and wild species,highlighting their evolutionary significance.Conclusions This is the first report unveiling a robust set of NUIs defining the pangenome of Bos indicus breeds of India.The analyses contribute valuable insights into the genomic landscape of desi cattle breeds.展开更多
Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first t...Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.展开更多
Background Copper(Cu)is a pervasive environmental pollutant with significant hepatotoxic effects in animals.The endoplasmic reticulum(ER)interacts closely with lysosomes to maintain intracellular homeostasis.However,t...Background Copper(Cu)is a pervasive environmental pollutant with significant hepatotoxic effects in animals.The endoplasmic reticulum(ER)interacts closely with lysosomes to maintain intracellular homeostasis.However,the role and mechanism of ER-lysosome crosstalk in Cu-induced liver injury in ducks remains unclear.To investigate this,we established both an in vivo model of Cu-exposed ducks and an in vitro model of duck hepatocytes,and added baicalin(Ba)to further explore its protective effects.Results The results of this study demonstrated that exposure to Cu resulted in vacuolar degeneration and oxidative stress in duck hepatocytes,while ultrastructural observations revealed ER swelling and an increased number of autophagic lysosomes.Furthermore,Cu exposure significantly upregulated mRNA and protein levels related to ER stress,autophagy,and lysosomal membrane factors.It also markedly increased ER-lysosomal co-localization.Further experiments showed that knockdown of LAPTM4B significantly attenuated Cu-induced ER autophagy and reduced ER-lysosomal co-localization in hepatocytes.Molecular docking and molecular dynamics simulations confirmed that LAPTM4B has a stable binding site to Ba;in vitro experiments demonstrated that Ba could effectively alleviate Cuinduced ER-lysosome crosstalk in duck hepatocytes and reduce hepatocyte injury by targeting LAPTM4B;additionally,in vivo experiments showed that Ba significantly inhibits Cu-induced liver injury in ducks.Conclusions In summary,the present study demonstrates that Cu exposure disrupts ER-lysosomal crosstalk in duck liver,leading to ER-lysosomal damage and subsequent hepatocyte injury.In contrast,Ba alleviates this injury by selectively targeting LAPTM4B,ultimately attenuating Cu-induced hepatotoxicity.展开更多
Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.N...Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prog-nosis in several types of tumors.Methods:We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells.We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer.The development of colorectal tumors were investigated using post-necropsy quantification,immunohistochemistry,and enzyme-linked immunosorbent assay(ELISA).Results:Compared with wild-type(WT)control mice,NSD2^(fl/fl)-Vil1-Cre mice exhib-ited significantly decreased tumor numbers,histopathological changes,and cytokine expression in colorectal tumors.Conclusions:Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.展开更多
Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA le...Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.展开更多
Background Necrotic enteritis(NE)can cause intestinal barrier dysfunction in broilers,leading to secondary liver injury(SLI).In this process,the gut-liver axis plays a crucial role.Lonicerae flos and turmeric extracts...Background Necrotic enteritis(NE)can cause intestinal barrier dysfunction in broilers,leading to secondary liver injury(SLI).In this process,the gut-liver axis plays a crucial role.Lonicerae flos and turmeric extracts(LTE),containing chlorogenic acid and curcumin,have been reported to possess anti-inflammatory,and antioxidant properties.Based on these potential biological benefits,this study aims to investigate the reparative effects of LTE on the intestinal barrier dysfunction in NE-infected broilers and assess its therapeutic efficacy in alleviating SLI.By elucidating the regulatory mechanisms of LTE on gut-liver axis health,this research provides new insights into the prevention and treatment of NE in broilers.Results LTE improved body weight and average daily gain while reducing intestinal lesion scores,coccidia oocysts,and Clostridium perfringens counts in NE broilers(P<0.05).LTE enhanced intestinal morphology and up-regulated the expression of tight junction protein genes(CLDN1,TJP1)and MUC2,suppressed pro-inflammatory cytokine and myeloperoxidase(MPO)levels,and minimized endotoxin(ET)accumulation in NE broilers(P<0.05).Furthermore,LTE alleviated oxidative stress in ileal cells and protected mitochondrial structure and function in NE broilers.NE infection induced intestinal permeability in broilers,leading to increased serum pro-inflammatory cytokines and intestinal-derived endotoxin levels,which caused liver damage.LTE significantly reduced liver pathologic damage,pro-inflammatory cytokine levels,aspartate transaminase,alanine aminotransferase,and ROS levels in NE broilers(P<0.05).Additionally,16S rRNA sequencing revealed that NE significantly increased the relative abundance of Barnesiella and decreased the relative abundance of Bacteroidota,Desulfobacterota and Bacteroides in the cecum of broilers.LTE enhanced intestinal microbiota diversity and reduced the segregation of intestinal microbiota induced by NE infection.Conclusions In summary,LTE can alleviate NE and SLI by modulating the microbiota,inhibiting inflammation and oxidative stress,and ameliorating mitochondrial dysfunction,thereby enhancing gut-liver axis health and growth performance.展开更多
Background Milk synthesis is an energy-intensive process influenced by oxygen availability.This study investigates how hypoxia affects milk synthesis in BMECs,focusing on key genes involved in lactation and energy met...Background Milk synthesis is an energy-intensive process influenced by oxygen availability.This study investigates how hypoxia affects milk synthesis in BMECs,focusing on key genes involved in lactation and energy metabolism.Methods BMECs were cultured in a normoxic environment and then transferred to a hypoxia chamber with 1%O2 for specified durations.The study evaluated cellular responses through various molecular experiments and RNA sequencing.Small interfering RNA was employed to knock down HIF-1αto investigate whether the lactation-related phenotype alteration depends on HIF-1α.Results Hypoxia disrupted milk protein production by reducing mTOR/P70S6K/4EBP1 signaling and downregulating genes critical for amino acid transport and protein synthesis.Triglyceride synthesis increased due to enhanced fatty acid uptake and the upregulation of regulatory proteins,including FASN and PPARγ.Although glucose uptake was elevated under hypoxia,key enzymes for lactose synthesis were downregulated,suggesting a redirection of glucose toward energy production.Mitochondrial function was impaired under hypoxia,with reduced gene expression in TCA cycle,ETC,cytosol-mitochondrial transport,decreased ATP levels,increased ROS levels,and structural alterations.Additionally,lipid synthesis and glucose uptake depend on HIF-1α,while milk protein synthesis alterations occurred independently of HIF-1α.Conclusions Hypoxia alters milk synthesis in BMECs by disrupting milk protein synthesis,enhancing lipid metabolism,and impairing energy production.These findings provide valuable insights into the molecular mechanisms underlying the effect of oxygen deprivation on lactation efficiency,offering potential targets for mitigating hypoxic stress in the mammary glands of dairy animals.展开更多
Background Oxidative stress significantly impacts growth performance and liver function in piglets.Ferulic acid(FA)works as an antioxidant,however,the role and mechanism of FA in the regulation of diquat-induced oxida...Background Oxidative stress significantly impacts growth performance and liver function in piglets.Ferulic acid(FA)works as an antioxidant,however,the role and mechanism of FA in the regulation of diquat-induced oxidative stress in piglets are less known.This study was designed to investigate the effects of FA on growth performance and antioxi-dant capacity in piglets with diquat challenge.Methods Thirty-two healthy DLY(Duroc×Landrace×Yorkshire)piglets(13.24±0.19 kg)were randomly divided into one of two diets including 0 or 4 g/kg FA for 14 d.On d 15,all pigs were intraperitoneally injected diquat or sterile saline.Results Dietary supplementation with ferulic acid(FA)significantly improved the average daily gain(ADG)and decreased feed-gain ratio(F/G)of piglets.Here,dietary FA supplementation reduced serum aspartate aminotrans-ferase(AST),alanine aminotransferase(ALT)activities in diquat challenged piglets.Furthermore,diquat infusion increased reactive oxygen radicals(ROS)level in liver,decreased the activities of total superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px),total antioxidant capacity(T-AOC)and increased malondialdehyde(MDA)con-tent in the liver and serum.Supplementation with FA significantly increased T-AOC and T-SOD activities and decreased MDA and ROS levels.FA down-regulated gene and protein expression of Keap1,and up-regulated protein expression of Nrf2 and HO-1 in the liver of piglets with diquat challenge.Importantly,diquat challenge increased the ratio of late apoptosis,increased serum levels of IL-1β,IL-18 and lactate dehydrogenase(LDH),and up-regulated pyroptosis-related genes in the liver.FA supplementation reduced the ratio of late apoptosis and down-regulated mRNA expression of Caspase-1.Accordingly,FA addition reduced concentration of IL-1β,IL-18,and LDH under diquat challenge.Conclusions Diquat-induced oxidative stress reduced growth performance and impaired liver function in piglets.Dietary FA supplementation enhanced the antioxidant capacity and reduced the degree of hepatocyte pyroptosis,thereby alleviating the oxidative damage in the liver and mitigating the impact of diquat on growth performance of piglets.展开更多
Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived mi...Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived miRNAs may play a key role in modulating embryonic oxidation-reduction process,whereas the exact function and mechanism were still poorly understood.The present study aimed to investigate the roles of egg exosome miRNAs in maintaining dynamic equilibrium of free radicals and peroxide agents in embryonic liver,as well as demonstrate the specific mechanism using oxidative stress-challenged hepatocytes.Results Compared to 36-week-old breeding hens,decreased hatchability and increased embryonic mortality were observed in 65-week-old breeding hens.Meanwhile,the older group showed the increased MDA levels and decreased SOD and GSH-Px activities in embryonic liver,muscle and serum.Embryonic mortality was significantly positively correlated with MDA level and negatively correlated with GSH-Px activity in embryonic liver.In addition,363 differentially expressed genes(DEGs)were identified in embryonic liver,13 differentially expressed miRNAs(DE-miRNAs)were identified in egg exosomes.These DEGs and DE-miRNAs were involved in oxidoreductase activity,glutathione metabolic process,MAPK signaling pathway,apoptosis and autophagy.miRNA-mRNA network analysis further found that DEGs targeted by DE-miRNAs were mainly enriched in programmed cell death,such as apoptosis and autophagy.Wherein,MAPK10 with highest MCC and AUC values was significantly related to GSH-Px activity and MDA level,and served as the target gene of miR-145-5p based on dual luciferase reporter experiment and correlation analysis.Bioinformatics analysis found that miR-145-5p/MAPK10 axis might alleviate peroxide generation and apoptosis.In primary hepatocytes of chick embryos,miR-145-5p transfection significantly reversed H_(2)O_(2)-induced mitochondrial ROS increase,MAPK10,BAX and CASP3 overexpression and excessive apoptosis.Conclusion Exosome miR-145-5p in eggs could target MAPK10 and decrease mitochondrial ROS,attenuating oxidative damage and apoptosis in hepatocytes of chick embryos.These findings may provide new theoretical basis for the improvement of maternal physiological status to maintain embryonic redox homeostasis by nutritional or genetic modifications.展开更多
Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biologic...Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biological functions as nutritional interventions.Despite the interest in organic acids and monoglycerides,few studies have examined the effects of the combination of these acid-based additives in weaned pigs under disease challenge conditions.Therefore,this study aimed to investigate the effects of dietary supplementation with blend of organic acids and/or medium-chain fatty acid monoglycerides on intestinal health and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC)F18 at 4-week of age.Results Dietary supplementation of organic acids,monoglycerides,or both organic acids and monoglycerides(combination)reduced(P<0.05)the diarrhea frequency of ETEC F18-infected pigs throughout the experimental period(d−7 to 21 post-inoculation).This is consistent with the reduced(P<0.05)proportion ofβ-hemolytic coliforms in feces observed for the organic acid and combination treatments on d 10 post-inoculation.Supplementation of organic acids,monoglycerides,or combination also reduced(P<0.05)bacterial translocation in mesenteric lymph nodes on d 21 post-inoculation.Pigs fed with monoglycerides or combination had lower(P<0.05)white blood cells on d 5 post-inoculation,and pigs fed the combination also had lower(P<0.05)lymphocytes than pigs in control group.Monoglyceride supplementation increased(P<0.05)white blood cells and neutrophils compared with control group on d 14 post-inoculation.However,supplementation with organic acid blend,monoglyceride blend,or combination did not affect growth performance in this experiment.Conclusions Supplementation with monoglycerides or organic acids alone or in combination improves the detrimental effects of ETEC F18 infection in weaned pigs,as indicated by reduced diarrhea,fecal shedding ofβ-hemolytic coliforms,and bacterial translocation,and thus enhancing disease resistance.Monoglycerides reduced the inflammatory response during peak infection,but their immunomodulatory and possible synergistic effects with organic acids need to be further investigated.展开更多
基金Youth Foundation of Higher Education Scientific Research of Hebei Province,China(No.2010228)Foundation for Returned Overseas Scholars of Hebei Province,China(No.C2013003015)
文摘Based upon motion capture,a semi-automatic technique for fast facial animation was implemented. While capturing the facial expressions from a performer,a camera was used to record her /his front face as a texture map. The radial basis function( RBF) technique was utilized to deform a generic facial model and the texture was remapped to generate a personalized face.Partitioning the personalized face into three regions and using the captured facial expression data,the RBF and Laplacian operator,and mean-value coordinates were implemented to deform each region respectively. With shape blending,the three regions were combined together to construct the final face model. Our results show that the technique is efficient in generating realistic facial animation.
文摘Why it needs to take the initiative in the shape in the painting？ Refine images of the shape of the objective initiatively, not only can enhance the artistic appeal and creators emotions, can also highlight the aesthetic orientation creators to make their paintings to impress the audience and resonate, so works of art have a higher aesthetic value. Similarly, in the entire animation movie, animation character modeling also has an important position, and a good cartoon must have a good role model to fully convey the story and character. This article attempts to analyze the shape of the image of the Disney animated start, make deep analysis on necessity of initiative modeling in the art of painting and development of initiative modeling, to enhance the performance of artists and diverse personality development, which is a requirement of modem art, but also the law of development of the arts.
基金financially supported by the Hainan Province Science and Technology Special Fund(Grant no:ZDYF2024XDNY187).
文摘Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.
基金supported by the Notional Natural Science Foundation of Chino,No.82160690Colloborotive Innovation Center of Chinese Ministry of Education,No.2020-39Science and Technology Foundation of Guizhou Province,No.ZK[2021]-014(all to FZ)。
文摘Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.
文摘The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.
基金supported by the National Key Research and Development Program(No.2021YFD1300201)Jilin Provincial Department of Science and Technology Innovation Platform and Talent Special Project(No.20230508090RC).
文摘Background There is a growing focus on using various plant-derived agricultural by-products to increase the benefits of pig farming,but these feedstuffs are fibrous in nature.This study investigated the relationship between dietary fiber physicochemical properties and feedstuff fermentation characteristics and their effects on nutrient utilization,energy metabolism,and gut microbiota in growing pigs.Methods Thirty-six growing barrows(47.2±1.5 kg)were randomly allotted to 6 dietary treatments with 2 apparent viscosity levels and 3β-glucan-to-arabinoxylan ratios.In the experiment,nutrient utilization,energy metabolism,fecal microbial community,and production and absorption of short-chain fatty acid(SCFA)of pigs were investigated.In vitro digestion and fermentation models were used to compare the fermentation characteristics of feedstuffs and ileal digesta in the pig’s hindgut.Results The production dynamics of SCFA and dry matter corrected gas production of different feedstuffs during in vitro fermentation were different and closely related to the physical properties and chemical structure of the fiber.In animal experiments,increasing the dietary apparent viscosity and theβ-glucan-to-arabinoxylan ratios both increased the apparent ileal digestibility(AID),apparent total tract digestibility(ATTD),and hindgut digestibility of fiber components while decreasing the AID and ATTD of dry matter and organic matter(P<0.05).In addition,increasing dietary apparent viscosity andβ-glucan-to-arabinoxylan ratios both increased gas exchange,heat production,and protein oxidation,and decreased energy deposition(P<0.05).The dietary apparent viscosity andβ-glucanto-arabinoxylan ratios had linear interaction effects on the digestible energy,metabolizable energy,retained energy(RE),and net energy(NE)of the diets(P<0.05).At the same time,the increase of dietary apparent viscosity andβ-glucan-to-arabinoxylan ratios both increased SCFA production and absorption(P<0.05).Increasing the dietary apparent viscosity andβ-glucan-to-arabinoxylan ratios increased the diversity and abundance of bacteria(P<0.05)and the relative abundance of beneficial bacteria.Furthermore,increasing the dietaryβ-glucan-to-arabinoxylan ratios led to a linear increase in SCFA production during the in vitro fermentation of ileal digesta(P<0.001).Finally,the prediction equations for RE and NE were established.Conclusion Dietary fiber physicochemical properties alter dietary fermentation patterns and regulate nutrient utilization,energy metabolism,and pig gut microbiota composition and metabolites.
基金supported by National Key R&D Program of China(2023YFD1301200)China Agriculture Research Systems(CARS-40-K11)+2 种基金Beijing Agriculture Innovation Consortium(BAIC06-2024-G05)Strategic Priority Research Program of the National Center of Technology Innovation for Pigs(NCTIP-XD/C08)The Chinese Academy of Agricultural Science and Technology Innovation Project(ASTIP-IAS-12)。
文摘Background Caffeic acid(CA)and its derivative,chlorogenic acid(CGA),have shown promise in preventing and alleviating fatty liver disease.CA,compared to CGA,has much lower production costs and higher bioavailability,making it a potentially superior feed additive.However,the efficacy,mechanistic differences,and comparative impacts of CA and CGA on fatty liver disease in laying hens remain unclear.This study aimed to evaluate and compare the effects of CA and CGA on production performance,egg quality,and fatty liver disease in laying hens.Results A total of 1,44061-week-old Hyline Brown laying hens were randomly divided into 8 groups and fed diets supplemented with basal diet,25,50,100 and 200 mg/kg of CA,and 100,200 and 400 mg/kg of CGA(CON,CA25,CA50,CA100,CA200,CGA100,CGA200 and CGA400,respectively)for 12 weeks.Both CA and CGA improved production performance and egg quality,while reducing markers of hepatic damage and lipid accumulation.CA and CGA significantly decreased TG,TC,and LDL-C levels and increased T-SOD activity.Transcriptomic and proteomic analyses revealed that CA and CGA reduced hepatic lipid accumulation through downregulation of lipid biosynthesis-related genes(ACLY,ACACA,FASN,and SCD1)and enhanced lipid transport and oxidation genes(FABPs,CD36,CPT1A,ACOX1,and SCP2).Of note,low-dose CA25 exhibited equivalent efficacy to the higher dose CGA100 group in alleviating fatty liver conditions.Mechanistically,CA and CGA alleviated lipid accumulation via activation of the ADPN-AMPK-PPARαsignaling pathway.Conclusions This study demonstrates that dietary CA and CGA effectively improve laying performance,egg quality,and hepatic lipid metabolism in laying hens,with CA potentially being more economical and efficient.Transcriptomic and proteomic evidence highlight shared mechanisms between CA25 and CGA100.These findings provide a foundation for CA and CGA as therapeutic agents for fatty liver disease and related metabolic diseases in hens,and also offer insights into the targeted modification of CGA(including the isomer of CGA)into CA,thereby providing novel strategies for the efficient utilization of CGA.Highlights(1)Dietary CA and CGA improve fatty liver,laying performance and egg quality.(2)Lower dose of CA25 achieves the equivalent improvement as CGA100 or CGA200.(3)CA and CGA mediate the ADPN-AMPK-PPARαpathway to alleviate fatty liver.
基金the project “Genomics for Conservation of Indigenous Cattle Breeds and for Enhancing Milk Yield, Phase-I” [BT/ PR26466/AAQ/1/704/2017], funded by the Department of Biotechnology (DBT ), Indiathe project “Identification of key molecular factors involved in resistance/susceptibility to paratuberculosis infection in indigenous breeds of cows” [BT/PR32758/AAQ/1/760/2019], which was also funded by Department of Biotechnology (DBT ), India。
文摘Background India harbors the world’s largest cattle population,encompassing over 50 distinct Bos indicus breeds.This rich genetic diversity underscores the inadequacy of a single reference genome to fully capture the genomic landscape of Indian cattle.To comprehensively characterize the genomic variation within Bos indicus and,specifically,dairy breeds,we aim to identify non-reference sequences and construct a comprehensive pangenome.Results Five representative genomes of prominent dairy breeds,including Gir,Kankrej,Tharparkar,Sahiwal,and Red Sindhi,were sequenced using 10X Genomics‘linked-read’technology.Assemblies generated from these linked-reads ranged from 2.70 Gb to 2.77 Gb,comparable to the Bos indicus Brahman reference genome.A pangenome of Bos indicus cattle was constructed by comparing the newly assembled genomes with the reference using alignment and graph-based methods,revealing 8 Mb and 17.7 Mb of novel sequence respectively.A confident set of 6,844 Non-reference Unique Insertions(NUIs)spanning 7.57 Mb was identified through both methods,representing the pange-nome of Indian Bos indicus breeds.Comparative analysis with previously published pangenomes unveiled 2.8 Mb(37%)commonality with the Chinese indicine pangenome and only 1%commonality with the Bos taurus pange-nome.Among these,2,312 NUIs encompassing~2 Mb,were commonly found in 98 samples of the 5 breeds and des-ignated as Bos indicus Common Insertions(BICIs)in the population.Furthermore,926 BICIs were identified within 682 protein-coding genes,54 long non-coding RNAs(lncRNA),and 18 pseudogenes.These protein-coding genes were enriched for functions such as chemical synaptic transmission,cell junction organization,cell-cell adhesion,and cell morphogenesis.The protein-coding genes were found in various prominent quantitative trait locus(QTL)regions,suggesting potential roles of BICIs in traits related to milk production,reproduction,exterior,health,meat,and carcass.Notably,63.21%of the bases within the BICIs call set contained interspersed repeats,predominantly Long Inter-spersed Nuclear Elements(LINEs).Additionally,70.28%of BICIs are shared with other domesticated and wild species,highlighting their evolutionary significance.Conclusions This is the first report unveiling a robust set of NUIs defining the pangenome of Bos indicus breeds of India.The analyses contribute valuable insights into the genomic landscape of desi cattle breeds.
基金supported by the National Natural Science Foundation of China Regional Joint Innovation Fund (No.U22A20524)the Heilongjiang Province Natural Science Foundation Key projects (No.ZD2023C002).
文摘Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.
基金supported by the program of Introduce and cultivate high-level innovative and entrepreneurial personnel:Thousand Talents Program of Jiangxi province(jxsg2023201121)the National Natural Science Foundation of China(32460908)Natural Science Foundation of Jiangxi province(20232ACB215004).
文摘Background Copper(Cu)is a pervasive environmental pollutant with significant hepatotoxic effects in animals.The endoplasmic reticulum(ER)interacts closely with lysosomes to maintain intracellular homeostasis.However,the role and mechanism of ER-lysosome crosstalk in Cu-induced liver injury in ducks remains unclear.To investigate this,we established both an in vivo model of Cu-exposed ducks and an in vitro model of duck hepatocytes,and added baicalin(Ba)to further explore its protective effects.Results The results of this study demonstrated that exposure to Cu resulted in vacuolar degeneration and oxidative stress in duck hepatocytes,while ultrastructural observations revealed ER swelling and an increased number of autophagic lysosomes.Furthermore,Cu exposure significantly upregulated mRNA and protein levels related to ER stress,autophagy,and lysosomal membrane factors.It also markedly increased ER-lysosomal co-localization.Further experiments showed that knockdown of LAPTM4B significantly attenuated Cu-induced ER autophagy and reduced ER-lysosomal co-localization in hepatocytes.Molecular docking and molecular dynamics simulations confirmed that LAPTM4B has a stable binding site to Ba;in vitro experiments demonstrated that Ba could effectively alleviate Cuinduced ER-lysosome crosstalk in duck hepatocytes and reduce hepatocyte injury by targeting LAPTM4B;additionally,in vivo experiments showed that Ba significantly inhibits Cu-induced liver injury in ducks.Conclusions In summary,the present study demonstrates that Cu exposure disrupts ER-lysosomal crosstalk in duck liver,leading to ER-lysosomal damage and subsequent hepatocyte injury.In contrast,Ba alleviates this injury by selectively targeting LAPTM4B,ultimately attenuating Cu-induced hepatotoxicity.
基金supported by the National Key Research and Development Program of China (2022YFF0710705)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-0 13)+2 种基金funding support from the Special Research Fund for Central UniversitiesPeking Union Medical College (3332022182)the 111 Project (B20095)
文摘Background:Nuclear receptor-binding SET domain 2(NSD2)is a histone methyltrans-ferase,that catalyzes dimethylation of lysine 36 of histone 3(H3K36me2)and is asso-ciated with active transcription of a series of genes.NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prog-nosis in several types of tumors.Methods:We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells.We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer.The development of colorectal tumors were investigated using post-necropsy quantification,immunohistochemistry,and enzyme-linked immunosorbent assay(ELISA).Results:Compared with wild-type(WT)control mice,NSD2^(fl/fl)-Vil1-Cre mice exhib-ited significantly decreased tumor numbers,histopathological changes,and cytokine expression in colorectal tumors.Conclusions:Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.
基金supported by the National Key R&D Program of China(2021YFD1300404)。
文摘Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.
基金provided by the precise assessment of the combined toxic effects of major mycotoxins on monogastric animals(2023YFD1301002).
文摘Background Necrotic enteritis(NE)can cause intestinal barrier dysfunction in broilers,leading to secondary liver injury(SLI).In this process,the gut-liver axis plays a crucial role.Lonicerae flos and turmeric extracts(LTE),containing chlorogenic acid and curcumin,have been reported to possess anti-inflammatory,and antioxidant properties.Based on these potential biological benefits,this study aims to investigate the reparative effects of LTE on the intestinal barrier dysfunction in NE-infected broilers and assess its therapeutic efficacy in alleviating SLI.By elucidating the regulatory mechanisms of LTE on gut-liver axis health,this research provides new insights into the prevention and treatment of NE in broilers.Results LTE improved body weight and average daily gain while reducing intestinal lesion scores,coccidia oocysts,and Clostridium perfringens counts in NE broilers(P<0.05).LTE enhanced intestinal morphology and up-regulated the expression of tight junction protein genes(CLDN1,TJP1)and MUC2,suppressed pro-inflammatory cytokine and myeloperoxidase(MPO)levels,and minimized endotoxin(ET)accumulation in NE broilers(P<0.05).Furthermore,LTE alleviated oxidative stress in ileal cells and protected mitochondrial structure and function in NE broilers.NE infection induced intestinal permeability in broilers,leading to increased serum pro-inflammatory cytokines and intestinal-derived endotoxin levels,which caused liver damage.LTE significantly reduced liver pathologic damage,pro-inflammatory cytokine levels,aspartate transaminase,alanine aminotransferase,and ROS levels in NE broilers(P<0.05).Additionally,16S rRNA sequencing revealed that NE significantly increased the relative abundance of Barnesiella and decreased the relative abundance of Bacteroidota,Desulfobacterota and Bacteroides in the cecum of broilers.LTE enhanced intestinal microbiota diversity and reduced the segregation of intestinal microbiota induced by NE infection.Conclusions In summary,LTE can alleviate NE and SLI by modulating the microbiota,inhibiting inflammation and oxidative stress,and ameliorating mitochondrial dysfunction,thereby enhancing gut-liver axis health and growth performance.
基金supported by grants from the National Natural Science Foundation of China(grant number:32072756)Agricultural Research System of China(grant number:CARS-36).
文摘Background Milk synthesis is an energy-intensive process influenced by oxygen availability.This study investigates how hypoxia affects milk synthesis in BMECs,focusing on key genes involved in lactation and energy metabolism.Methods BMECs were cultured in a normoxic environment and then transferred to a hypoxia chamber with 1%O2 for specified durations.The study evaluated cellular responses through various molecular experiments and RNA sequencing.Small interfering RNA was employed to knock down HIF-1αto investigate whether the lactation-related phenotype alteration depends on HIF-1α.Results Hypoxia disrupted milk protein production by reducing mTOR/P70S6K/4EBP1 signaling and downregulating genes critical for amino acid transport and protein synthesis.Triglyceride synthesis increased due to enhanced fatty acid uptake and the upregulation of regulatory proteins,including FASN and PPARγ.Although glucose uptake was elevated under hypoxia,key enzymes for lactose synthesis were downregulated,suggesting a redirection of glucose toward energy production.Mitochondrial function was impaired under hypoxia,with reduced gene expression in TCA cycle,ETC,cytosol-mitochondrial transport,decreased ATP levels,increased ROS levels,and structural alterations.Additionally,lipid synthesis and glucose uptake depend on HIF-1α,while milk protein synthesis alterations occurred independently of HIF-1α.Conclusions Hypoxia alters milk synthesis in BMECs by disrupting milk protein synthesis,enhancing lipid metabolism,and impairing energy production.These findings provide valuable insights into the molecular mechanisms underlying the effect of oxygen deprivation on lactation efficiency,offering potential targets for mitigating hypoxic stress in the mammary glands of dairy animals.
基金Sichuan Science and Technology Program(No.2021ZDZX0009).
文摘Background Oxidative stress significantly impacts growth performance and liver function in piglets.Ferulic acid(FA)works as an antioxidant,however,the role and mechanism of FA in the regulation of diquat-induced oxidative stress in piglets are less known.This study was designed to investigate the effects of FA on growth performance and antioxi-dant capacity in piglets with diquat challenge.Methods Thirty-two healthy DLY(Duroc×Landrace×Yorkshire)piglets(13.24±0.19 kg)were randomly divided into one of two diets including 0 or 4 g/kg FA for 14 d.On d 15,all pigs were intraperitoneally injected diquat or sterile saline.Results Dietary supplementation with ferulic acid(FA)significantly improved the average daily gain(ADG)and decreased feed-gain ratio(F/G)of piglets.Here,dietary FA supplementation reduced serum aspartate aminotrans-ferase(AST),alanine aminotransferase(ALT)activities in diquat challenged piglets.Furthermore,diquat infusion increased reactive oxygen radicals(ROS)level in liver,decreased the activities of total superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px),total antioxidant capacity(T-AOC)and increased malondialdehyde(MDA)con-tent in the liver and serum.Supplementation with FA significantly increased T-AOC and T-SOD activities and decreased MDA and ROS levels.FA down-regulated gene and protein expression of Keap1,and up-regulated protein expression of Nrf2 and HO-1 in the liver of piglets with diquat challenge.Importantly,diquat challenge increased the ratio of late apoptosis,increased serum levels of IL-1β,IL-18 and lactate dehydrogenase(LDH),and up-regulated pyroptosis-related genes in the liver.FA supplementation reduced the ratio of late apoptosis and down-regulated mRNA expression of Caspase-1.Accordingly,FA addition reduced concentration of IL-1β,IL-18,and LDH under diquat challenge.Conclusions Diquat-induced oxidative stress reduced growth performance and impaired liver function in piglets.Dietary FA supplementation enhanced the antioxidant capacity and reduced the degree of hepatocyte pyroptosis,thereby alleviating the oxidative damage in the liver and mitigating the impact of diquat on growth performance of piglets.
基金supported by China Agriculture Research System of MOF and MARA(CARS-40)the National Natural Science Foundation of China(32302776)。
文摘Background Higher embryonic mortality,especially in aged breeding hens,is associated with insufficient hepatic functionality in maintaining redox homeostasis.Our previous study demonstrated that egg exosome-derived miRNAs may play a key role in modulating embryonic oxidation-reduction process,whereas the exact function and mechanism were still poorly understood.The present study aimed to investigate the roles of egg exosome miRNAs in maintaining dynamic equilibrium of free radicals and peroxide agents in embryonic liver,as well as demonstrate the specific mechanism using oxidative stress-challenged hepatocytes.Results Compared to 36-week-old breeding hens,decreased hatchability and increased embryonic mortality were observed in 65-week-old breeding hens.Meanwhile,the older group showed the increased MDA levels and decreased SOD and GSH-Px activities in embryonic liver,muscle and serum.Embryonic mortality was significantly positively correlated with MDA level and negatively correlated with GSH-Px activity in embryonic liver.In addition,363 differentially expressed genes(DEGs)were identified in embryonic liver,13 differentially expressed miRNAs(DE-miRNAs)were identified in egg exosomes.These DEGs and DE-miRNAs were involved in oxidoreductase activity,glutathione metabolic process,MAPK signaling pathway,apoptosis and autophagy.miRNA-mRNA network analysis further found that DEGs targeted by DE-miRNAs were mainly enriched in programmed cell death,such as apoptosis and autophagy.Wherein,MAPK10 with highest MCC and AUC values was significantly related to GSH-Px activity and MDA level,and served as the target gene of miR-145-5p based on dual luciferase reporter experiment and correlation analysis.Bioinformatics analysis found that miR-145-5p/MAPK10 axis might alleviate peroxide generation and apoptosis.In primary hepatocytes of chick embryos,miR-145-5p transfection significantly reversed H_(2)O_(2)-induced mitochondrial ROS increase,MAPK10,BAX and CASP3 overexpression and excessive apoptosis.Conclusion Exosome miR-145-5p in eggs could target MAPK10 and decrease mitochondrial ROS,attenuating oxidative damage and apoptosis in hepatocytes of chick embryos.These findings may provide new theoretical basis for the improvement of maternal physiological status to maintain embryonic redox homeostasis by nutritional or genetic modifications.
基金supported by Animal Nutrition,Eastman Chemical Company,Kingsport,TN,USA.
文摘Background The emergence of antibiotic resistant microorganisms associated with conventional swine production practices has increased interest in acid-based compounds having antimicrobial properties and other biological functions as nutritional interventions.Despite the interest in organic acids and monoglycerides,few studies have examined the effects of the combination of these acid-based additives in weaned pigs under disease challenge conditions.Therefore,this study aimed to investigate the effects of dietary supplementation with blend of organic acids and/or medium-chain fatty acid monoglycerides on intestinal health and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC)F18 at 4-week of age.Results Dietary supplementation of organic acids,monoglycerides,or both organic acids and monoglycerides(combination)reduced(P<0.05)the diarrhea frequency of ETEC F18-infected pigs throughout the experimental period(d−7 to 21 post-inoculation).This is consistent with the reduced(P<0.05)proportion ofβ-hemolytic coliforms in feces observed for the organic acid and combination treatments on d 10 post-inoculation.Supplementation of organic acids,monoglycerides,or combination also reduced(P<0.05)bacterial translocation in mesenteric lymph nodes on d 21 post-inoculation.Pigs fed with monoglycerides or combination had lower(P<0.05)white blood cells on d 5 post-inoculation,and pigs fed the combination also had lower(P<0.05)lymphocytes than pigs in control group.Monoglyceride supplementation increased(P<0.05)white blood cells and neutrophils compared with control group on d 14 post-inoculation.However,supplementation with organic acid blend,monoglyceride blend,or combination did not affect growth performance in this experiment.Conclusions Supplementation with monoglycerides or organic acids alone or in combination improves the detrimental effects of ETEC F18 infection in weaned pigs,as indicated by reduced diarrhea,fecal shedding ofβ-hemolytic coliforms,and bacterial translocation,and thus enhancing disease resistance.Monoglycerides reduced the inflammatory response during peak infection,but their immunomodulatory and possible synergistic effects with organic acids need to be further investigated.
