Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid ...Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid and nutrient components between the adipose tissue of Bamei pigs and commercial pigs are still unclear.The study employed UPLC-MS/MS to quantify the composition of lipids and metabolites in the backfat of both Bamei and Large White pigs.A total of 428 lipids and 193 metabolites were significantly different between the 2 groups.Specifically,Bamei pig backfat exhibited altered levels of various lipids and metabolites that may potentially contribute to nutritional and flavor differences,including unsaturated triglycerides,free fatty acids,medium-chain triglycerides,essential amino acids,vitamins and antioxidants,while maintaining reduced cholesterol levels.Furthermore,we delved into the molecular mechanisms underlying these nutritional differences by analyzing significantly different 431 m RNAs and 865 proteins and integrating the regulatory network of protein-metabolite-lipid pathway.Importantly,in the pyruvate metabolic pathway of Bamei pigs,the bioprocess of lactate production was inhibited but the acetyl-Co A production was activated,suggesting the possibility that energy allocation favors the biogenesis of lipid precursors.These findings may contribute to guiding industrial food producers in enhancing the quality of lard at the genetic and molecular levels.展开更多
Understanding the molecular responses of tea leaves to mechanical stress is crucial for elucidating the mechanisms of post-harvest quality formation during oolong tea processing.This study employed an integrated multi...Understanding the molecular responses of tea leaves to mechanical stress is crucial for elucidating the mechanisms of post-harvest quality formation during oolong tea processing.This study employed an integrated multi-omics strategy to characterize the changes and interactions among metabolomic(MB),transcriptomic(TX),and proteomic(PT)profiles in mechanically stressed tea leaves.Mechanical stress initially activated damage-associated molecular patterns(DAMPs),including Ca^(2+)signaling,jasmonic acid signaling,and glutathione metabolism pathways.These processes subsequently induced quality-related metabolic pathways(QRMPs),particularly α-linolenic acid and phenylalanine metabolism.Upregulated expression of LOX,ADH1,and PAR genes,together with the increased abundance of their encoded proteins,respectively promoted the accumulation of jasmine lactone,benzyl alcohol,and 2-phenylethanol.These findings indicate that mechanical stress influences the metabolite biosynthesis in tea leaves through coordinated molecular responses.This study provides new insights into the molecular mechanisms underlying tea leaf responses to mechanical stress and a foundation for future investigations into how early molecular events may contribute to post-harvest metabolic changes during oolong tea processing.展开更多
For chromosome abnormalities(CAs),such as Down syndrome(DS),the influence of genomic variations on chromosome conformation and gene transcription remains elusive.Based on the complete genomic sequences from the parent...For chromosome abnormalities(CAs),such as Down syndrome(DS),the influence of genomic variations on chromosome conformation and gene transcription remains elusive.Based on the complete genomic sequences from the parents of a DS trisomy patient,we systematically delineated an atlas of parental-specific,haplotype-resolved single nucleotide polymorphisms(SNPs),copy number variations(CNVs),threedimensional(3D)genome architecture,and RNA expression profiles in the diencephalon of the DS patient.The integrated haplotype-resolved multi-omics analysis demonstrated that one-dimensional(1D)genomic variations including SNPs and CNVs in the DS patient are highly correlated with the alterations in the 3D genome organization and the subsequent changes in gene transcription.This correlation remains valid at the haplotype level.Moreover,we revealed the 3D genome alteration-associated dysregulation of DS-related genes,which facilitates understanding the pathogenesis of CAs.Together,our study contributes to deciphering the coding from 1D genomic variations to 3D genome architecture and the subsequent gene transcription outcomes in both health and disease.展开更多
BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patien...BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.展开更多
Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterize...Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterized.This study aims to systematically explore the expression patterns,clinical significance,and immune-related functions of NUDT19 in various cancer types through multi-omics analysis,further revealing its potential role in cancer,particularly its functional and therapeutic target value in leukemia.Methods To achieve this goal,various bioinformatics approaches were employed to evaluate the expression patterns,clinical significance,and immune-related functions of NUDT19 in tumors and normal tissues.Additionally,we analyzed the mutation characteristics of NUDT19 and its relationship with epigenetic modifications.Using the single-cell analysis tool SingleCellBase,we explored the distribution of NUDT19 across different cell subpopulations in tumors.To validate these findings,qRT-PCR was used to measure NUDT19 expression levels in specific tumor cell lines,and we established acute myeloid leukemia(AML)cell lines(HL-60 and THP-1)to conduct NUDT19 knockdown and overexpression experiments,assessing its effects on leukemia cell proliferation,apoptosis,and invasion.Results Pan-cancer analysis revealed the dysregulated expression of NUDT19 across multiple cancer types,which was closely associated with poor prognosis,clinical staging,and diagnostic markers.Furthermore,NUDT19 was significantly correlated with tumor biomarkers,immune-related genes,and immune cell infiltration in different cancers.Mutation analysis showed that multiple mutations in NUDT19 were significantly associated with epigenetic changes.Single-cell analysis revealed the heterogeneity of NUDT19 expression in cancer cells,suggesting its potentially diverse functional roles in different cell subpopulations.qRT-PCR experiments confirmed the significant upregulation of NUDT19 in various tumor cell lines.In AML cell lines,NUDT19 knockdown led to reduced cell proliferation and invasion,with increased apoptosis,while NUDT19 overexpression significantly enhanced cell proliferation and invasion while reducing apoptosis.Conclusion This study demonstrates the diverse roles of NUDT19 in various cancer types,with a particularly prominent functional role in leukemia.NUDT19 is not only associated with tumor initiation and progression but may also influence cancer progression through the regulation of immune microenvironment and epigenetic mechanisms.Our research highlights the potential of NUDT19 as a therapeutic target,particularly for targeted therapies in malignancies such as leukemia,with significant clinical application prospects.展开更多
Body weight is a polygenic trait with intricate inheritance patterns.Functional genomics enriched with multi-layer annotations offers essential resources for exploring the genetic architecture of complex traits.In thi...Body weight is a polygenic trait with intricate inheritance patterns.Functional genomics enriched with multi-layer annotations offers essential resources for exploring the genetic architecture of complex traits.In this study,we conducted an extensive characterization of regulatory variants associated with body weight-related traits in cattle using multi-omics analysis.First,we identified seven candidate genes by integrating selective sweep analysis and multiple genome-wide association study(GWAS)strategies using imputed whole-genome sequencing data from a population of 1577 individuals.Subsequently,we uncovered 3340 eGenes(genes whose expression levels are associated with genetic variants)across 227 muscle samples.Transcriptome-wide association studies(TWASs)further revealed a total of 532 distinct candidate genes associated with body weight-related traits.Colocalization analyses unveiled 44 genes shared between expression quantitative trait loci(eQTLs)and GWAS signals.Moreover,a comprehensive analysis by integrating GWAS,selective sweep,eQTL,TWAS,epigenomic profiling,and molecular validation highlighted a positively selected genomic region on Bos taurus autosome 6(BTA6).This locus harbors pleiotropic genes(LAP3,MED28,and NCAPG)and a prioritized functional variant involved in the complex regulation of body weight.Additionally,convergent evolution analysis and phenome-wide association studies underscored the conservation of this locus across species.Our study provides a comprehensive understanding of the genetic regulation of body weight through multi-omics analysis in cattle.Our findings contribute to unraveling the genetic mechanisms governing weight-related traits and shed valuable light on the genetic improvement of farm animals.展开更多
Background As an indigenous livestock species on the Tibetan Plateau,Tibetan sheep exhibit remarkable adaptability to low temperatures and nutrient-scarce environments.During the cold season,Tibetan sheep are typicall...Background As an indigenous livestock species on the Tibetan Plateau,Tibetan sheep exhibit remarkable adaptability to low temperatures and nutrient-scarce environments.During the cold season,Tibetan sheep are typically managed under two feeding regimes:barn feeding(BF)and traditional grazing(TG).However,the molecular mechanisms underlying their adaptation to these distinct management strategies remain unclear.This study aimed to investigate the adaptive strategies of rumen function in Tibetan sheep to cold-season feeding regimes by integrating analyses of rumen morphology,microbiome,metabolome,and transcriptome.Twelve healthy Tibetan sheep with similar body weights were assigned into two groups(BF vs.TG).At the end of the experiment,rumen tissues were subjected to histological observation.Multi-omics techniques were employed to evaluate the effects of cold-season feeding regimes on rumen function in Tibetan sheep.Results The ruminal papilla height,width,and muscular thickness were significantly higher in BF group.The relative abundances of Actinobacteria and Succiniclasticum were significantly elevated in the rumen of BF group,whereas Rikenellaceae,Gracilibacteria,and Lachnospiraceae showed higher abundances in the TG group.Metabolomic analysis identified 19 differential metabolites between the two groups,including upregulated compounds in BF group(fumaric acid,maltose,L-phenylalanine,and L-alanine)and TG group(e.g.,phenylacetic acid,salicyluric acid and ferulic acid).These metabolites were predominantly enriched in phenylalanine metabolism,alanine,aspartate and glutamate metabolism,and phenylalanine,tyrosine and tryptophan biosynthesis pathways.Additionally,210 differentially expressed genes(DEGs)were identified in rumen epithelium:100 upregulated DEGs in the BF group were enriched in nutrient metabolism-related pathways(e.g.,fatty acid degradation and PPAR signaling pathway),while 110 upregulated DEGs in the TG group were associated with immune-related pathways(e.g.,p53 signaling pathway and glutathione metabolism).Conclusions Among these,we observed distinct rumen functional responses to different cold-season feeding regimes in Tibetan sheep and revealed energy allocation strategies mediated by host-microbe interactions.In the BF group,Tibetan sheep adopted a"metabolic efficiency-priority"strategy,driving rumen microbiota to maximize energy capture from high-nutrient diets to support host growth.In contrast,the TG group exhibited an"environmental adaptation-priority"strategy,where rumen microbiota prioritized cellulose degradation and anti-inflammatory functions,reallocating energy toward homeostasis maintenance at the expense of rumen development and growth performance.展开更多
Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty...Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated.Multi-omics analyses,including microarray analysis,single-cell RNA sequencing(scRNA-seq),and metabolomics,were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.Results identified ACSL6,ACSBG2,and OLAH as key genes linked to fatty acid metabolism dysregulation,suggesting their potential causative roles in NOA.A marked reduction in omega-3 polyunsaturated fatty acids,especially docosahexaenoic acid(DHA),was observed,potentially contributing to the pathological process of NOA.Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction,with PPARG identified as a key transcription factor(TF)regulating this process.Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB)integrity and promoting spermatogenesis via regulation of fatty acid metabolism.These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.展开更多
Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,mili...Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.Methods:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise regimen.Omics profiles post-vs.pre-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics modalities.Results:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of samples.The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands.The urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid balance.In saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.Conclusions:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.展开更多
Sesquiterpene valencene is dominant in flavedo tissues of sweet oranges and imparts a unique woody aroma.However,the interaction between the biosynthetic pathways of valencene and other nutritional compounds is less s...Sesquiterpene valencene is dominant in flavedo tissues of sweet oranges and imparts a unique woody aroma.However,the interaction between the biosynthetic pathways of valencene and other nutritional compounds is less studied.Sesquiterpenoids were significantly accumulated in a previously reported glossy mutant of orange(MT)than the wild type(WT),especially valencene and caryophyllene.In addition,we identified several other pathways with variations at both the transcriptional and metabolic levels in MT.It’s interesting to found those upregulated metabolites in MT,such as eukaryotic lipids,kaempferol and proline also showed strong positive correlation with valencene along with fruit maturation while those down-regulated metabolites,such as phenylpropanoid coumarins and most of the modified flavonoids exhibited negative correlation.We then categorized these shifted pathways into the‘sesquitepenoid-identical shunt’and the sesquitepenoid-opposite shunt’and confirmed the classification result at transcriptional level.Our results provide important insights into the connections between various fruit quality-related properties.展开更多
Accurate genomic information is essential for advancing genetic breeding research in specific rice varieties.This study presented a gapless genome assembly of the indica rice cultivar Zhonghui 8015(ZH8015)using Pac Bi...Accurate genomic information is essential for advancing genetic breeding research in specific rice varieties.This study presented a gapless genome assembly of the indica rice cultivar Zhonghui 8015(ZH8015)using Pac Bio HiFi,Hi-C,and ONT(Oxford Nanopore Technologies)ultra-long sequencing technologies,annotating 43037 gene structures.Subsequently,utilizing this genome along with transcriptomic and metabolomic techniques,we explored ZH8015's response to brown planthopper(BPH)infestation.Continuous transcriptomic sampling indicated significant changes in gene expression levels around 48 h after BPH feeding.Enrichment analysis revealed particularly significant alterations in genes related to reactive oxygen species scavenging and cell wall formation.Metabolomic results demonstrated marked increases in levels of several monosaccharides,which are components of the cell wall and dramatic changes in flavonoid contents.Omics association analysis identified differentially expressed genes associated with key metabolites,shedding light on ZH8015's response to BPH infestation.In summary,this study constructed a reliable genome sequence resource for ZH8015,and the preliminary multi-omics results will guide future insect-resistant breeding research.展开更多
BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains el...BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains elusive.AIM To investigate comprehensively the molecular process of esophageal cancer.METHODS Differential expression analysis was performed to identify differentially expressed genes(DEGs)in different stages of esophageal cancer from The Cancer Genome Atlas data.Exacting gene interaction modules were generated,and hub genes in the module interaction network were found.Further,through survival analysis,methylation analysis,pivot analysis,and enrichment analysis,some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.RESULTS A total of 7457 DEGs and 14 gene interaction modules were identified.These module genes were significantly involved in the positive regulation of protein transport,gastric acid secretion,insulin-like growth factor receptor binding,and other biological processes as well as p53 signaling pathway,epidermal growth factor signaling pathway,and epidermal growth factor receptor signaling pathway.Transcription factors(including hypoxia inducible factor 1A)and noncoding RNAs(including colorectal differentially expressed and hsa-miR-330-3p)that significantly regulate dysfunction modules were identified.Survival analysis showed that G protein subunit gamma transducin 2(GNGT2)was closely related to survival of esophageal cancer.DEGs with strong methylation regulation ability were identified,including SST and SH3GL2.Furthermore,the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction,and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines.Moreover,cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.CONCLUSION This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.展开更多
Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recogni...Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.展开更多
Prior exposure to microbial-associated molecular patterns or specific chemical compounds can promote plants into a primed state with stronger defence responses.β-aminobutyric acid(BABA)is an endogenous stress metabol...Prior exposure to microbial-associated molecular patterns or specific chemical compounds can promote plants into a primed state with stronger defence responses.β-aminobutyric acid(BABA)is an endogenous stress metabolite that induces resistance protecting various plants towards diverse stresses.In this study,by integrating BABA-induced changes in selected metabolites with transcriptome and proteome data,we generated a global map of the molecular processes operating in BABA-induced resistance(BABA-IR)in tomato.BABA significantly restricts the growth of the pathogens Oidium neolycopersici and Phytophthora parasitica but not Botrytis cinerea.A cluster analysis of the upregulated processes showed that BABA acts mainly as a stress factor in tomato.The main factor distinguishing BABA-IR from other stress conditions was the extensive induction of signaling and perception machinery playing a key role in effective resistance against pathogens.Interestingly,the signalling processes and immune response activated during BABA-IR in tomato differed from those in Arabidopsis with substantial enrichment of genes associated with jasmonic acid(JA)and ethylene(ET)signalling and no change in Asp levels.Our results revealed key differences between the effect of BABA on tomato and other model plants studied until now.Surprisingly,salicylic acid(SA)is not involved in BABA downstream signalization whereas ET and JA play a crucial role.展开更多
BACKGROUND Angiogenesis plays an important role in colon cancer(CC)progression.AIM To investigate the tumor microenvironment(TME)and intratumor microbes of angiogenesis subtypes(AGSs)and explore potential targets for ...BACKGROUND Angiogenesis plays an important role in colon cancer(CC)progression.AIM To investigate the tumor microenvironment(TME)and intratumor microbes of angiogenesis subtypes(AGSs)and explore potential targets for antiangiogenic therapy in CC.METHODS The data were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database.K-means clustering was used to construct the AGSs.The prognostic model was constructed based on the differential genes between two subtypes.Single-cell analysis was used to analyze the expression level of SLC2A3 on different cells in CC,which was validated by immunofluorescence.Its biological functions were further explored in HUVECs.RESULTS CC samples were grouped into two AGSs(AGS-A and AGS-B)groups and patients in the AGS-B group had poor prognosis.Further analysis revealed that the AGS-B group had high infiltration of TME immune cells,but also exhibited high immune escape.The intratumor microbes were also different between the two subtypes.A convenient 6-gene angiogenesis-related signature(ARS),was established to identify AGSs and predict the prognosis in CC patients.SLC2A3 was selected as the representative gene of ARS,which was higher expressed in endothelial cells and promoted the migration of HUVECs.CONCLUSION Our study identified two AGSs with distinct prognoses,TME,and intratumor microbial compositions,which could provide potential explanations for the impact on the prognosis of CC.The reliable ARS model was further constructed,which could guide the personalized treatment.The SLC2A3 might be a potential target for antiangiogenic therapy.展开更多
Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through...Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.展开更多
Atemoya fruit,prized for their flavor and nutritional value,are susceptible to rapid postharvest deterioration,particularly peel browning,limiting their marketability.This browning process,often linked to oxidative st...Atemoya fruit,prized for their flavor and nutritional value,are susceptible to rapid postharvest deterioration,particularly peel browning,limiting their marketability.This browning process,often linked to oxidative stress and cell wall degradation,remains poorly understood at the molecular level.This study investigated the impact of modified atmosphere packaging(MAP)on atemoya peel browning during cold storage using integrated biochemical,metabolomic,and transcriptomic analyses.Results demonstrated that MAP effectively reduced browning index and extended shelf-life by 12 days.Multi-omics analysis revealed that MAP elevated antioxidant enzyme activities and ascorbic acid accumulation while delaying cell wall degradation.Notably,pectinesterase-encoding genes showed strong correlation with ascorbate and phenylpropanoid metabolism.These findings provide new insights into the molecular basis of MAP-mediated browning reduction in atemoya and suggest potential targets for postharvest quality improvement.展开更多
Background:The CUG-binding protein Elav-like family member 2(CELF2)gene has been linked to the pathogenesis of epilepsy,but its precise role remains unclear.This study aimed to investigate the pathogenic mechanisms of...Background:The CUG-binding protein Elav-like family member 2(CELF2)gene has been linked to the pathogenesis of epilepsy,but its precise role remains unclear.This study aimed to investigate the pathogenic mechanisms of CELF2 mutation in epilepsy,utilizing zebrafish models to explore its molecular pathways and biological impact.Methods:Whole-exome sequencing was performed to identify CELF2mutations associated with epilepsy.CELF2 zebrafish model was generated using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-related protein 9technology and morpholinos,followed by behavioral and electroencephalographic analyses to confirm epileptic phenotypes.Proteomic and metabolomic analyses were conducted to examine the impact of CELF2 deficiency on metabolic pathways,and single-cell sequencing was used to assess alterations in neuronal cell populations.Results:An infant with infantile epileptic spasms syndrome associated with a CELF2(p.Pro520Arg)gene mutation was reported.We established zebrafish models with celf2 gene knockout and knockdown and found that zebrafish with celf2mutations exhibited epilepsy-like behaviors,which could be rescued by injection of CELF2 wild-type mRNA.Significant changes were observed in crucial marker genes associated with the nervous system in the celf2^(+/−)group,including FOS,BDNF,NPAS4,GABRA1,GABRG2,and PYYA.Disruptions in lipid metabolism,heat shock protein 90 beta1(Hsp90b1),were identified in proteomic and metabolomic analyses.Single-cell sequencing showed changes in nucleosome localization,nucleosome DNA binding,arginine and proline metabolic pathways,gonadotropin-releasing hormone signaling pathway,and nucleotide-binding oligomerization domain receptor signaling pathway.Conclusions:Our study has revealed a promising association between defects in the CELF2 gene and epilepsy using a zebrafish model,suggesting that CLEF2 is a causative gene in epilepsy.These findings not only indicate the potential impact on the biological process influenced by the CELF2 gene defect but also offer hopeful insights into the pathogenesis of epilepsy and potential therapeutic targets.展开更多
Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The ...Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The primary endpoints have been met in clinical trials of belimumab involving patients with active SLE without severe organ complications,as well as in trials involving patients with lupus nephritis.In addition,the effects of belimumab in preventing relapses and reducing glucocorticoid use have been confirmed.Moreover,there were no significant differences in the incidences of many adverse events between the belimumab and placebo groups.Recent multiomics analyses have revealed that the cells targeted by belimumab are limited to naïve B cells and a subset of memory B cells.These findings align with the efficacy and safety profile of belimumab.An improved understanding of the mechanism of action of belimumab could support its use earlier during the treatment course or in a broader range of SLE cases.展开更多
Understanding plant-pathogen interactions requires a systems-level perspective that single-omics approaches,such as genomics,transcriptomics,proteomics,or metabolomics alone,often fail to provide.While these methods a...Understanding plant-pathogen interactions requires a systems-level perspective that single-omics approaches,such as genomics,transcriptomics,proteomics,or metabolomics alone,often fail to provide.While these methods are informative,they are limited in their ability to capture the complexity of the dynamic molecular interactions between host and pathogen.Multi-omics strategies offer a powerful solution by integrating complementary data types,enabling a more comprehensive view of the molecular networks and pathways involved in disease progression and defence.Although technological advances have made omics analyses more accessible and affordable,their integration remains underutilised in plant science.This review highlights the limitations of single-omics studies in dissecting plant-pathogen interactions and emphasises the value of multi-omics approaches.We discuss available computational tools for data integration and visualisation,outline current challenges,including data heterogeneity,normalisation issues,and computational demands,and explore future directions such as the exploitation of artificial intelligence-based approaches and single-cell omics.We conclude that the increasing accessibility and affordability of omics analysis means that multi-omics strategies are now indispensable tools to investigate complex biological processes such as plant-pathogen interactions.展开更多
基金supported by the National Key Research and Development Program of China(2021YFF1000602)the National Natural Science Foundations(32202642)the earmarked fund for CARS-35-PIG.
文摘Bamei pigs,an indigenous Chinese breed,yield meat with a delectable flavor and boast higher carcass fat content compared to commercial breeds,making them a rich food source for humans.However,the differences in lipid and nutrient components between the adipose tissue of Bamei pigs and commercial pigs are still unclear.The study employed UPLC-MS/MS to quantify the composition of lipids and metabolites in the backfat of both Bamei and Large White pigs.A total of 428 lipids and 193 metabolites were significantly different between the 2 groups.Specifically,Bamei pig backfat exhibited altered levels of various lipids and metabolites that may potentially contribute to nutritional and flavor differences,including unsaturated triglycerides,free fatty acids,medium-chain triglycerides,essential amino acids,vitamins and antioxidants,while maintaining reduced cholesterol levels.Furthermore,we delved into the molecular mechanisms underlying these nutritional differences by analyzing significantly different 431 m RNAs and 865 proteins and integrating the regulatory network of protein-metabolite-lipid pathway.Importantly,in the pyruvate metabolic pathway of Bamei pigs,the bioprocess of lactate production was inhibited but the acetyl-Co A production was activated,suggesting the possibility that energy allocation favors the biogenesis of lipid precursors.These findings may contribute to guiding industrial food producers in enhancing the quality of lard at the genetic and molecular levels.
基金supported by the National Key Research and Development Program of China(2022YFD2101101)the Earmarked Fund for CARS-19+2 种基金the National Natural Science Foundation of China(32402634)the Modern Agricultural(Tea)Industry Technology System of Fujian Province,China(2025 No.593)the Special Fund for Science and Technology Innovation of Fujian Zhang Tianfu Tea Development Foundation,China(FJZTF01)。
文摘Understanding the molecular responses of tea leaves to mechanical stress is crucial for elucidating the mechanisms of post-harvest quality formation during oolong tea processing.This study employed an integrated multi-omics strategy to characterize the changes and interactions among metabolomic(MB),transcriptomic(TX),and proteomic(PT)profiles in mechanically stressed tea leaves.Mechanical stress initially activated damage-associated molecular patterns(DAMPs),including Ca^(2+)signaling,jasmonic acid signaling,and glutathione metabolism pathways.These processes subsequently induced quality-related metabolic pathways(QRMPs),particularly α-linolenic acid and phenylalanine metabolism.Upregulated expression of LOX,ADH1,and PAR genes,together with the increased abundance of their encoded proteins,respectively promoted the accumulation of jasmine lactone,benzyl alcohol,and 2-phenylethanol.These findings indicate that mechanical stress influences the metabolite biosynthesis in tea leaves through coordinated molecular responses.This study provides new insights into the molecular mechanisms underlying tea leaf responses to mechanical stress and a foundation for future investigations into how early molecular events may contribute to post-harvest metabolic changes during oolong tea processing.
基金supported by the National Natural Science Foundation of China(Grant Nos.32221005 to Gang Cao and 81900063 to He Long)the Natural Science Foundation of Hubei Province,China(Grant No.2022CFB180 to Zhijun Zhang).
文摘For chromosome abnormalities(CAs),such as Down syndrome(DS),the influence of genomic variations on chromosome conformation and gene transcription remains elusive.Based on the complete genomic sequences from the parents of a DS trisomy patient,we systematically delineated an atlas of parental-specific,haplotype-resolved single nucleotide polymorphisms(SNPs),copy number variations(CNVs),threedimensional(3D)genome architecture,and RNA expression profiles in the diencephalon of the DS patient.The integrated haplotype-resolved multi-omics analysis demonstrated that one-dimensional(1D)genomic variations including SNPs and CNVs in the DS patient are highly correlated with the alterations in the 3D genome organization and the subsequent changes in gene transcription.This correlation remains valid at the haplotype level.Moreover,we revealed the 3D genome alteration-associated dysregulation of DS-related genes,which facilitates understanding the pathogenesis of CAs.Together,our study contributes to deciphering the coding from 1D genomic variations to 3D genome architecture and the subsequent gene transcription outcomes in both health and disease.
基金Supported by WBE Liver Foundation,No.WBE20220182022 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYY-YN-2022-092023 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYYYN2023-14.
文摘BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.
文摘Objective Recent studies have highlighted the critical role of NUDT19 in the initiation,progression,and prognosis of specific cancer types.However,its involvement in pan-cancer analysis has not been fully characterized.This study aims to systematically explore the expression patterns,clinical significance,and immune-related functions of NUDT19 in various cancer types through multi-omics analysis,further revealing its potential role in cancer,particularly its functional and therapeutic target value in leukemia.Methods To achieve this goal,various bioinformatics approaches were employed to evaluate the expression patterns,clinical significance,and immune-related functions of NUDT19 in tumors and normal tissues.Additionally,we analyzed the mutation characteristics of NUDT19 and its relationship with epigenetic modifications.Using the single-cell analysis tool SingleCellBase,we explored the distribution of NUDT19 across different cell subpopulations in tumors.To validate these findings,qRT-PCR was used to measure NUDT19 expression levels in specific tumor cell lines,and we established acute myeloid leukemia(AML)cell lines(HL-60 and THP-1)to conduct NUDT19 knockdown and overexpression experiments,assessing its effects on leukemia cell proliferation,apoptosis,and invasion.Results Pan-cancer analysis revealed the dysregulated expression of NUDT19 across multiple cancer types,which was closely associated with poor prognosis,clinical staging,and diagnostic markers.Furthermore,NUDT19 was significantly correlated with tumor biomarkers,immune-related genes,and immune cell infiltration in different cancers.Mutation analysis showed that multiple mutations in NUDT19 were significantly associated with epigenetic changes.Single-cell analysis revealed the heterogeneity of NUDT19 expression in cancer cells,suggesting its potentially diverse functional roles in different cell subpopulations.qRT-PCR experiments confirmed the significant upregulation of NUDT19 in various tumor cell lines.In AML cell lines,NUDT19 knockdown led to reduced cell proliferation and invasion,with increased apoptosis,while NUDT19 overexpression significantly enhanced cell proliferation and invasion while reducing apoptosis.Conclusion This study demonstrates the diverse roles of NUDT19 in various cancer types,with a particularly prominent functional role in leukemia.NUDT19 is not only associated with tumor initiation and progression but may also influence cancer progression through the regulation of immune microenvironment and epigenetic mechanisms.Our research highlights the potential of NUDT19 as a therapeutic target,particularly for targeted therapies in malignancies such as leukemia,with significant clinical application prospects.
基金supported by the National Key R&D Program of China(Grant No.2022YFF1000600)the National Natural Science Foundation of China(Grant No.31972554)+4 种基金supported by the Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(Grant Nos.ASTIP-IAS-TS-16 and ASTIP-IAS03)the National Beef Cattle Industrial Technology System(Grant No.CARS-37)supported in part by the Agriculture and Food Research Initiative(AFRI)(Grant Nos.2019-67015-29321 and 2021-67015-33409)from the United States Department of Agriculture(USDA)National Institute of Food and Agriculture(NIFA)Animal Genome and Reproduction ProgramsLingyang Xu was supported by the Elite Youth Scientists Program of the Chinese Academy of Agricultural Sciences.
文摘Body weight is a polygenic trait with intricate inheritance patterns.Functional genomics enriched with multi-layer annotations offers essential resources for exploring the genetic architecture of complex traits.In this study,we conducted an extensive characterization of regulatory variants associated with body weight-related traits in cattle using multi-omics analysis.First,we identified seven candidate genes by integrating selective sweep analysis and multiple genome-wide association study(GWAS)strategies using imputed whole-genome sequencing data from a population of 1577 individuals.Subsequently,we uncovered 3340 eGenes(genes whose expression levels are associated with genetic variants)across 227 muscle samples.Transcriptome-wide association studies(TWASs)further revealed a total of 532 distinct candidate genes associated with body weight-related traits.Colocalization analyses unveiled 44 genes shared between expression quantitative trait loci(eQTLs)and GWAS signals.Moreover,a comprehensive analysis by integrating GWAS,selective sweep,eQTL,TWAS,epigenomic profiling,and molecular validation highlighted a positively selected genomic region on Bos taurus autosome 6(BTA6).This locus harbors pleiotropic genes(LAP3,MED28,and NCAPG)and a prioritized functional variant involved in the complex regulation of body weight.Additionally,convergent evolution analysis and phenome-wide association studies underscored the conservation of this locus across species.Our study provides a comprehensive understanding of the genetic regulation of body weight through multi-omics analysis in cattle.Our findings contribute to unraveling the genetic mechanisms governing weight-related traits and shed valuable light on the genetic improvement of farm animals.
基金funded by the Chief Scientist Program of Qinghai Province(2024-SF-102)the Joint Special Project of Sanjiangyuan National Park(LHZX-2023-02).
文摘Background As an indigenous livestock species on the Tibetan Plateau,Tibetan sheep exhibit remarkable adaptability to low temperatures and nutrient-scarce environments.During the cold season,Tibetan sheep are typically managed under two feeding regimes:barn feeding(BF)and traditional grazing(TG).However,the molecular mechanisms underlying their adaptation to these distinct management strategies remain unclear.This study aimed to investigate the adaptive strategies of rumen function in Tibetan sheep to cold-season feeding regimes by integrating analyses of rumen morphology,microbiome,metabolome,and transcriptome.Twelve healthy Tibetan sheep with similar body weights were assigned into two groups(BF vs.TG).At the end of the experiment,rumen tissues were subjected to histological observation.Multi-omics techniques were employed to evaluate the effects of cold-season feeding regimes on rumen function in Tibetan sheep.Results The ruminal papilla height,width,and muscular thickness were significantly higher in BF group.The relative abundances of Actinobacteria and Succiniclasticum were significantly elevated in the rumen of BF group,whereas Rikenellaceae,Gracilibacteria,and Lachnospiraceae showed higher abundances in the TG group.Metabolomic analysis identified 19 differential metabolites between the two groups,including upregulated compounds in BF group(fumaric acid,maltose,L-phenylalanine,and L-alanine)and TG group(e.g.,phenylacetic acid,salicyluric acid and ferulic acid).These metabolites were predominantly enriched in phenylalanine metabolism,alanine,aspartate and glutamate metabolism,and phenylalanine,tyrosine and tryptophan biosynthesis pathways.Additionally,210 differentially expressed genes(DEGs)were identified in rumen epithelium:100 upregulated DEGs in the BF group were enriched in nutrient metabolism-related pathways(e.g.,fatty acid degradation and PPAR signaling pathway),while 110 upregulated DEGs in the TG group were associated with immune-related pathways(e.g.,p53 signaling pathway and glutathione metabolism).Conclusions Among these,we observed distinct rumen functional responses to different cold-season feeding regimes in Tibetan sheep and revealed energy allocation strategies mediated by host-microbe interactions.In the BF group,Tibetan sheep adopted a"metabolic efficiency-priority"strategy,driving rumen microbiota to maximize energy capture from high-nutrient diets to support host growth.In contrast,the TG group exhibited an"environmental adaptation-priority"strategy,where rumen microbiota prioritized cellulose degradation and anti-inflammatory functions,reallocating energy toward homeostasis maintenance at the expense of rumen development and growth performance.
基金supported by the National Natural Science Foundation of China (U22A20277,81971373)Jiangsu Provincial Medical Key Discipline Cultivation Unit (JSDW202215)+1 种基金333 High-level Personnel Training Project of Jiangsu Province (BRA2019109)Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX22_1826)。
文摘Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated.Multi-omics analyses,including microarray analysis,single-cell RNA sequencing(scRNA-seq),and metabolomics,were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.Results identified ACSL6,ACSBG2,and OLAH as key genes linked to fatty acid metabolism dysregulation,suggesting their potential causative roles in NOA.A marked reduction in omega-3 polyunsaturated fatty acids,especially docosahexaenoic acid(DHA),was observed,potentially contributing to the pathological process of NOA.Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction,with PPARG identified as a key transcription factor(TF)regulating this process.Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB)integrity and promoting spermatogenesis via regulation of fatty acid metabolism.These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.
基金supported by the BRAVE Agile Investment from the PNNL
文摘Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.Methods:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise regimen.Omics profiles post-vs.pre-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics modalities.Results:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of samples.The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands.The urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid balance.In saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.Conclusions:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.
基金financed by the National Natural Science Foundation of China (31772261)the Huazhong Agricultural University Scientific & Technological Self-Innovation Foundation (Program No.2017RC002) to Dr. Weiwei Wen
文摘Sesquiterpene valencene is dominant in flavedo tissues of sweet oranges and imparts a unique woody aroma.However,the interaction between the biosynthetic pathways of valencene and other nutritional compounds is less studied.Sesquiterpenoids were significantly accumulated in a previously reported glossy mutant of orange(MT)than the wild type(WT),especially valencene and caryophyllene.In addition,we identified several other pathways with variations at both the transcriptional and metabolic levels in MT.It’s interesting to found those upregulated metabolites in MT,such as eukaryotic lipids,kaempferol and proline also showed strong positive correlation with valencene along with fruit maturation while those down-regulated metabolites,such as phenylpropanoid coumarins and most of the modified flavonoids exhibited negative correlation.We then categorized these shifted pathways into the‘sesquitepenoid-identical shunt’and the sesquitepenoid-opposite shunt’and confirmed the classification result at transcriptional level.Our results provide important insights into the connections between various fruit quality-related properties.
基金supported by the Chinese Academy of Agricultural Sciences Innovation Project(Grant No.CAASASTIP-2013CNRRI)Fundamental Research Funds for Central Public Welfare Research Institutes of Chinese Rice Research Institute(Grant No.CPSIBRF-CNRRI-202102)。
文摘Accurate genomic information is essential for advancing genetic breeding research in specific rice varieties.This study presented a gapless genome assembly of the indica rice cultivar Zhonghui 8015(ZH8015)using Pac Bio HiFi,Hi-C,and ONT(Oxford Nanopore Technologies)ultra-long sequencing technologies,annotating 43037 gene structures.Subsequently,utilizing this genome along with transcriptomic and metabolomic techniques,we explored ZH8015's response to brown planthopper(BPH)infestation.Continuous transcriptomic sampling indicated significant changes in gene expression levels around 48 h after BPH feeding.Enrichment analysis revealed particularly significant alterations in genes related to reactive oxygen species scavenging and cell wall formation.Metabolomic results demonstrated marked increases in levels of several monosaccharides,which are components of the cell wall and dramatic changes in flavonoid contents.Omics association analysis identified differentially expressed genes associated with key metabolites,shedding light on ZH8015's response to BPH infestation.In summary,this study constructed a reliable genome sequence resource for ZH8015,and the preliminary multi-omics results will guide future insect-resistant breeding research.
基金Supported by Construction of Engineering Laboratory of Jilin Development and Reform Commission(grant no.3J115AK93429)Jilin Provincial Science and Technology Department Medical Health Project(grant no.3D5195001429)
文摘BACKGROUND Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world.Although a series of studies on esophageal cancer have been reported,the molecular pathogenesis of the disease remains elusive.AIM To investigate comprehensively the molecular process of esophageal cancer.METHODS Differential expression analysis was performed to identify differentially expressed genes(DEGs)in different stages of esophageal cancer from The Cancer Genome Atlas data.Exacting gene interaction modules were generated,and hub genes in the module interaction network were found.Further,through survival analysis,methylation analysis,pivot analysis,and enrichment analysis,some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer.RESULTS A total of 7457 DEGs and 14 gene interaction modules were identified.These module genes were significantly involved in the positive regulation of protein transport,gastric acid secretion,insulin-like growth factor receptor binding,and other biological processes as well as p53 signaling pathway,epidermal growth factor signaling pathway,and epidermal growth factor receptor signaling pathway.Transcription factors(including hypoxia inducible factor 1A)and noncoding RNAs(including colorectal differentially expressed and hsa-miR-330-3p)that significantly regulate dysfunction modules were identified.Survival analysis showed that G protein subunit gamma transducin 2(GNGT2)was closely related to survival of esophageal cancer.DEGs with strong methylation regulation ability were identified,including SST and SH3GL2.Furthermore,the expression of GNGT2 was evaluated by quantitative real time polymerase chain reaction,and the results showed that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines.Moreover,cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines.CONCLUSION This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.
基金supported by the National Natural Science Foundation of China(No.82172408)Shanghai Jiao Tong University Medical College“Two-hundred Talent”Program(No.20191829)+1 种基金The Second Three-Year Action Plan for Promoting Clinical Skills and Clinical Innovation in Municipal Hospitals of Shanghai Shenkang(No.SHDC2020CR4032)Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration(No.20DZ2254100).
文摘Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.
基金This project was supported by the National Infrastructure France Genomique(Commissariat aux Grands Investissements,ANR-10-INBS-09-03,ANR-10-INBS-09-02).
文摘Prior exposure to microbial-associated molecular patterns or specific chemical compounds can promote plants into a primed state with stronger defence responses.β-aminobutyric acid(BABA)is an endogenous stress metabolite that induces resistance protecting various plants towards diverse stresses.In this study,by integrating BABA-induced changes in selected metabolites with transcriptome and proteome data,we generated a global map of the molecular processes operating in BABA-induced resistance(BABA-IR)in tomato.BABA significantly restricts the growth of the pathogens Oidium neolycopersici and Phytophthora parasitica but not Botrytis cinerea.A cluster analysis of the upregulated processes showed that BABA acts mainly as a stress factor in tomato.The main factor distinguishing BABA-IR from other stress conditions was the extensive induction of signaling and perception machinery playing a key role in effective resistance against pathogens.Interestingly,the signalling processes and immune response activated during BABA-IR in tomato differed from those in Arabidopsis with substantial enrichment of genes associated with jasmonic acid(JA)and ethylene(ET)signalling and no change in Asp levels.Our results revealed key differences between the effect of BABA on tomato and other model plants studied until now.Surprisingly,salicylic acid(SA)is not involved in BABA downstream signalization whereas ET and JA play a crucial role.
基金Supported by Beijing Science and Technology Program,No.Z211100002921028Capital’s Funds for Health Improvement and Research,No.CFH2022-2-2025。
文摘BACKGROUND Angiogenesis plays an important role in colon cancer(CC)progression.AIM To investigate the tumor microenvironment(TME)and intratumor microbes of angiogenesis subtypes(AGSs)and explore potential targets for antiangiogenic therapy in CC.METHODS The data were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database.K-means clustering was used to construct the AGSs.The prognostic model was constructed based on the differential genes between two subtypes.Single-cell analysis was used to analyze the expression level of SLC2A3 on different cells in CC,which was validated by immunofluorescence.Its biological functions were further explored in HUVECs.RESULTS CC samples were grouped into two AGSs(AGS-A and AGS-B)groups and patients in the AGS-B group had poor prognosis.Further analysis revealed that the AGS-B group had high infiltration of TME immune cells,but also exhibited high immune escape.The intratumor microbes were also different between the two subtypes.A convenient 6-gene angiogenesis-related signature(ARS),was established to identify AGSs and predict the prognosis in CC patients.SLC2A3 was selected as the representative gene of ARS,which was higher expressed in endothelial cells and promoted the migration of HUVECs.CONCLUSION Our study identified two AGSs with distinct prognoses,TME,and intratumor microbial compositions,which could provide potential explanations for the impact on the prognosis of CC.The reliable ARS model was further constructed,which could guide the personalized treatment.The SLC2A3 might be a potential target for antiangiogenic therapy.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2025ZFJH03)the Central Guidance Fund for Local Science and Technology Development(No.2024ZY01054)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-045).
文摘Background:Giant cell arteritis(GCA),the most common systemic vasculitis affecting elderly individuals,currently lacks specific therapies.This study aimed to systematically identify therapeutic targets for GCA through integration of large-scale multi-omics datasets.Methods:We constructed a multi-stage analytical framework encompassing 32 proteomic datasets(covering 2914 unique plasma proteins)and 6 transcriptomic datasets.Multi-omics integration strategies,including two-sample Mendelian randomization,colocalization analysis,and functional enrichment analysis,were employed to identify and validate causal relationships between candidate targets and GCA risk across 4 independent European-ancestry GCA cohorts.Single-cell RNA sequencing analysis of peripheral blood mononuclear cells from untreated GCA patients was performed to characterize hub gene-immune cell relationships.Results:We identified 43 plasma proteins causally associated with GCA[false discovery rate(FDR)<0.05],with 17 representing novel therapeutic targets.Through dual validation using proteome-wide association studies and transcriptome-wide association studies,we identified 13 high-confidence candidate targets with distinct tissue-specific expression patterns.Unc-51 like kinase 3(ULK3)emerged as the strongest protective factor(odds ratio=0.47,95%confidence interval:0.37–0.71)through autophagy regulation,while SLAMF7 represents an immediate drug repositioning opportunity as the target of food and drug administration-approved elotuzumab.Five targets have existing approved drugs(SLAMF7,ICAM1,IL18,IL6ST,CTSS).Single-cell analysis revealed profound disruption of hub gene-immune cell relationships in untreated GCA patients,with cell-type-specific alterations in inflammatory gene expression,and TYMP as the most critical hub gene.Conclusions:This study provides a clinically-actionable atlas of 43 potential therapeutic targets in GCA,identifying novel mechanisms including autophagy modulation and metabolic reprogramming,with immediate drug repositioning opportunities and precision medicine strategies based on tissue-specific and cell-type-specific expression patterns.These findings require experimental validation before clinical translation.
基金supported by Yunnan Major Science&Technology Programs(202102AE090015)Yunnan Department of Science and Technology Innovation Guidance and Technology Enterprise Cultivation Plan(202204BP090031)National Natural Science Foundation of China(32072270).
文摘Atemoya fruit,prized for their flavor and nutritional value,are susceptible to rapid postharvest deterioration,particularly peel browning,limiting their marketability.This browning process,often linked to oxidative stress and cell wall degradation,remains poorly understood at the molecular level.This study investigated the impact of modified atmosphere packaging(MAP)on atemoya peel browning during cold storage using integrated biochemical,metabolomic,and transcriptomic analyses.Results demonstrated that MAP effectively reduced browning index and extended shelf-life by 12 days.Multi-omics analysis revealed that MAP elevated antioxidant enzyme activities and ascorbic acid accumulation while delaying cell wall degradation.Notably,pectinesterase-encoding genes showed strong correlation with ascorbate and phenylpropanoid metabolism.These findings provide new insights into the molecular basis of MAP-mediated browning reduction in atemoya and suggest potential targets for postharvest quality improvement.
基金supported by grants from the National Science Foundation of China(Nos.82071686 and 82271692)the Clinical Research Fund of West China Second University Hospital(Nos.KL115 and KL072)the Natural Science Foundation of Sichuan Province(No.2022NSFSC0782).
文摘Background:The CUG-binding protein Elav-like family member 2(CELF2)gene has been linked to the pathogenesis of epilepsy,but its precise role remains unclear.This study aimed to investigate the pathogenic mechanisms of CELF2 mutation in epilepsy,utilizing zebrafish models to explore its molecular pathways and biological impact.Methods:Whole-exome sequencing was performed to identify CELF2mutations associated with epilepsy.CELF2 zebrafish model was generated using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-related protein 9technology and morpholinos,followed by behavioral and electroencephalographic analyses to confirm epileptic phenotypes.Proteomic and metabolomic analyses were conducted to examine the impact of CELF2 deficiency on metabolic pathways,and single-cell sequencing was used to assess alterations in neuronal cell populations.Results:An infant with infantile epileptic spasms syndrome associated with a CELF2(p.Pro520Arg)gene mutation was reported.We established zebrafish models with celf2 gene knockout and knockdown and found that zebrafish with celf2mutations exhibited epilepsy-like behaviors,which could be rescued by injection of CELF2 wild-type mRNA.Significant changes were observed in crucial marker genes associated with the nervous system in the celf2^(+/−)group,including FOS,BDNF,NPAS4,GABRA1,GABRG2,and PYYA.Disruptions in lipid metabolism,heat shock protein 90 beta1(Hsp90b1),were identified in proteomic and metabolomic analyses.Single-cell sequencing showed changes in nucleosome localization,nucleosome DNA binding,arginine and proline metabolic pathways,gonadotropin-releasing hormone signaling pathway,and nucleotide-binding oligomerization domain receptor signaling pathway.Conclusions:Our study has revealed a promising association between defects in the CELF2 gene and epilepsy using a zebrafish model,suggesting that CLEF2 is a causative gene in epilepsy.These findings not only indicate the potential impact on the biological process influenced by the CELF2 gene defect but also offer hopeful insights into the pathogenesis of epilepsy and potential therapeutic targets.
基金supported by The Center of Innovation Program from the Japan Science and Technology Agency(JST),Grant/Award Number:JPMJCE1304 to Keishi FujioThe Ministry of Education,Culture,Sports,and the Japan Agency for Medical Research and Development(AMED),Grant/Award Numbers:JP21zf0127004,JP21tm0424221,JP22ek0410074,JP22fa627001,JP23fa627001,JP23gm1810005 to Keishi FujioJSPS Grant-in-Aid for Scientific Research(B),Grant/Award Numbers:JP19H03697,JP22H03110,JP23K24369 to Tomohisa Okamura,Chugai Pharmaceutical Co.,Ltd.,Tokyo,Japan.
文摘Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The primary endpoints have been met in clinical trials of belimumab involving patients with active SLE without severe organ complications,as well as in trials involving patients with lupus nephritis.In addition,the effects of belimumab in preventing relapses and reducing glucocorticoid use have been confirmed.Moreover,there were no significant differences in the incidences of many adverse events between the belimumab and placebo groups.Recent multiomics analyses have revealed that the cells targeted by belimumab are limited to naïve B cells and a subset of memory B cells.These findings align with the efficacy and safety profile of belimumab.An improved understanding of the mechanism of action of belimumab could support its use earlier during the treatment course or in a broader range of SLE cases.
文摘Understanding plant-pathogen interactions requires a systems-level perspective that single-omics approaches,such as genomics,transcriptomics,proteomics,or metabolomics alone,often fail to provide.While these methods are informative,they are limited in their ability to capture the complexity of the dynamic molecular interactions between host and pathogen.Multi-omics strategies offer a powerful solution by integrating complementary data types,enabling a more comprehensive view of the molecular networks and pathways involved in disease progression and defence.Although technological advances have made omics analyses more accessible and affordable,their integration remains underutilised in plant science.This review highlights the limitations of single-omics studies in dissecting plant-pathogen interactions and emphasises the value of multi-omics approaches.We discuss available computational tools for data integration and visualisation,outline current challenges,including data heterogeneity,normalisation issues,and computational demands,and explore future directions such as the exploitation of artificial intelligence-based approaches and single-cell omics.We conclude that the increasing accessibility and affordability of omics analysis means that multi-omics strategies are now indispensable tools to investigate complex biological processes such as plant-pathogen interactions.
