Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More r...Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.展开更多
The sedimentary ecosystems of deep-sea floors harbor abundant biological resources,with fungi emerging as predominant eukaryotic taxa that perform crucial ecological roles.However,the adaptive strategies enabling fung...The sedimentary ecosystems of deep-sea floors harbor abundant biological resources,with fungi emerging as predominant eukaryotic taxa that perform crucial ecological roles.However,the adaptive strategies enabling fungal survival in these extreme low-oxygen environments remain poorly understood.We elucidated the hypoxic adaptation mechanisms of Chaetomium globosum YP-106,an oxygen-sensitive fungus isolated from 6215-m deep seawater in Yap Trench in the western Pacific.Under hypoxic conditions,the strain growth rate was reduced with significant mycelial morphological alterations.Multi-omics analyses revealed 313 differentially abundant metabolites(DAMs)and 661 differential expression genes(DEGs),enriched in mainly fatty acid metabolism(degradation/synthesis)and carbohydrate utilization pathways.It is noteworthy that gene ontology(GO)enrichment analysis identified 171 membrane-associated genes,suggesting that structural membrane remodeling may serve as a key adaptive strategy.Integrated pathway analysis demonstrated metabolic reprogramming characterized by suppressed tricarboxylic acid(TCA)cycle activity and preferential activation of anaerobic glycolysis for ATP production.Importantly,the NADH dehydrogenase-mediated NAD+regeneration was enhanced as a compensatory mechanism sustaining residual TCA cycle function.These findings elucidated hypoxic metabolic mechanisms in deep-sea ascomycetes,enhanced our understanding of microbial energy conservation strategies in oxygen-deprived environments,and offered novel perspectives on eukaryotic extremophile adaptation mechanisms in benthic ecosystems.展开更多
Ustiloxins are the primary secondary metabolites of Ustilaginoidea virens(teleomorph:Villosiclava virens).While these toxins are known to exhibit toxicity in certain animals,their potential risks to human health requi...Ustiloxins are the primary secondary metabolites of Ustilaginoidea virens(teleomorph:Villosiclava virens).While these toxins are known to exhibit toxicity in certain animals,their potential risks to human health require further investigation.Therefore,this study was conducted using male mice as experimental animal to explore their potential health risks.We observed morphological changes in cells and structural lesions in mitochondria using electron microscopy,combined with Hematoxylin and Eosin(H&E)staining.We utilized transcriptomics,proteomics,and bioinformatics techniques to analyze the regulatory networks associated with ustiloxins in the context of liver damage and study the mechanism of liver injury caused by ustiloxins in mice.Differentially expressed genes(DEGs)were linked to terms such as‘metabolism of exogenous substances with cytochrome P450’,‘peroxisomes’,and‘negative regulation of the inflammatory response’.Western blotting and quantitative real-time PCR(qRT-PCR)demonstrated that ustiloxins can further activate the inflammatory pathways of Nrf2/HO-1 and NLRP3 by activating cytochrome P450(CYP450),leading to liver damage in mice.展开更多
Drought severely affects sustainable agricultural production worldwide.Upland rice ecotypes perform favorably under drought conditions;however,the underlying mechanisms remain largely unclear.In this study,we investig...Drought severely affects sustainable agricultural production worldwide.Upland rice ecotypes perform favorably under drought conditions;however,the underlying mechanisms remain largely unclear.In this study,we investigated changes in the transcriptome,metabolome,and physio-biochemical attributes of rice subjected to drought and supplemented with nitric oxide(NO)and hydrogen sulfide(H2S).Drought stress reduced growth and triggered lipid peroxidation;however,NO and H2S application alleviated the growth decline and lipid peroxidation.In addition,NO and H2S upregulated the activity of antioxidant enzymes,thereby mitigating the drought-induced oxidative stress.展开更多
Anthocyanins play a crucial role in plant growth,development,reproduction,and stress response.Additionally,anthocyanins enhance the quality of fruits and vegetables due to their antioxidant properties.While numerous p...Anthocyanins play a crucial role in plant growth,development,reproduction,and stress response.Additionally,anthocyanins enhance the quality of fruits and vegetables due to their antioxidant properties.While numerous previous studies have been conducted on anthocyanins,limited information exists regarding their composition and the role of the anthocyanin pathway gene dihydroflavonol 4-reductase(DFR) in chili pepper leaves.In this study,we used a purple leaf pepper cultivar H18 in which the anthocyanin content in leaves decreases with plant growth and development.Targeted anthocyanin metabolite assays revealed that the contents of delphinidin,malvidin,and petunidin derivatives followed the same trend as the overall anthocyanin content,with delphinidin derivatives being the predominant component of H18pepper leaves.Transcriptome sequencing was performed on H18 leaves at four different stages.The results showed that differentially expressed genes(DEGs) at various stages were primarily associated with biological processes and flavonoid metabolic pathways.Through phylogenetic tree and expression analysis,we identified three candidate genes involved in DFR function.Substrate catalysis assays of CaDFRs demonstrated that only CaDFR1 was active,catalyzing dihydroquercetin(DHQ),dihydromyricetin(DHM),and dihydrokaempferol(DHK).VIGS-mediated silencing of CaDFR1resulted in a significant decrease in anthocyanin levels in H18 pepper leaves and stems,along with a reduction in the expression levels of other candidate functional genes in the anthocyanin metabolic pathway.This study identifies the key anthocyanin components in the leaves of H18 peppers and validates the function of CaDFR1,providing a theoretical foundation for modifying anthocyanin content in pepper plants through molecular breeding.展开更多
Salinization affects over 800 million hectares of irrigated land globally.As a typical salt-sensitive crop,rice(Oryza sativa L.)suffers from high ionic stress,elevated osmotic pressure,and excessive accumulation of re...Salinization affects over 800 million hectares of irrigated land globally.As a typical salt-sensitive crop,rice(Oryza sativa L.)suffers from high ionic stress,elevated osmotic pressure,and excessive accumulation of reactive oxygen species(ROS)in saline soils,resulting in growth inhibition(Goyal et al.,2021;Jia et al.,2022).Salt tolerance in rice involves complex mechanisms across morphological,physiological,and molecular levels(Zhu,2016;Alkahtani and Dwiningsih,2023;Li et al.,2024).展开更多
Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on ...Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on repairing skeletal muscle injuries has been rarely reported.In this study,a mouse model of muscle injury was constructed and found that OVA significantly increased muscle weight,muscle thickness,and exercise capacity in muscle-injured mice.Meanwhile,OVA improved the morphology of muscle tissues by reducing serum levels of urea nitrogen,creatine kinase,and lactate dehydrogenase,as well as decreasing the levels of inflammatory factors interleukin(IL)-1β,tumor necrosis factor α,and IL-6,respectively.In addition,transcriptomic and metabolomic analyses revealed that OVA could enhance muscle tissue morphology by upregulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and improving amino acid metabolism through the upregulation of Col11a2,Ccn2,Thbs1,Tnc,Klf2,Bcl2l1,Adh3a1,and Rsad1.The study provided a theoretical foundation for understanding the molecular mechanisms in OVA-aided muscle injury repair.展开更多
Background:Partial epithelial-mesenchymal transition(p-EMT)is a dynamic cellular state associated with metastasis and adverse outcomes in multiple cancers,but its prognostic significance in ovarian cancer remains uncl...Background:Partial epithelial-mesenchymal transition(p-EMT)is a dynamic cellular state associated with metastasis and adverse outcomes in multiple cancers,but its prognostic significance in ovarian cancer remains unclear.This study aimed to develop and validate an ovarian cancer-specific transcriptomic signature based on p-EMT-related genes,and to determine whether this signature can improve prognostic stratification and overall survival prediction across independent cohorts.Methods:A pan-cancer p-EMT gene set was curated from ten published studies.Using transcriptomic and clinical data from TCGA-OV(n=488),a six-gene p-EMT signature was developed via LASSO regression to generate a patient-specific risk score.The score was integrated with clinical variables to construct a prognostic nomogram and validated in the external GEO cohort GSE140082(n=380)and GSE165808(n=51).Results:A six-gene p-EMT transcriptomic signature(ADAM9,ANXA8L1,FSTL3,RABAC1,TPM4,and TWIST1)was significantly associated with overall survival(OS)and stratified patients into high-and low-risk groups(adjusted HR=1.74,p<0.001).Incorporation with age and FIGO stage in a nomogram improved predictive performance,with AUCs of 0.727,0.700,and 0.656 at 1-,3-,and 5-year OS,respectively.External validation in GSE140082 and GSE165808 confirmed model robustness,yielding 3-year AUCs of 0.630 and 0.826,respectively,demonstrating preserved prognostic value across independent cohorts and disease stages.Conclusions:This six-gene p-EMT transcriptomic signature demonstrates prognostic value in ovarian cancer and offers potential for individualized risk stratification and clinical decisionsupport.展开更多
Rheumatoid arthritis(RA)is a common long-term autoimmune disease that causes synovial tissue to grow and behave like a tumor when inflammatory factors are present.This can cause joint pain,muscle loss,and other seriou...Rheumatoid arthritis(RA)is a common long-term autoimmune disease that causes synovial tissue to grow and behave like a tumor when inflammatory factors are present.This can cause joint pain,muscle loss,and other serious problems.Therefore,finding natural anti-RA products and effective treatment strategies is crucial for achieving good prognoses in RA patients.The deer bone is rich in protein,which has the effect of eliminating rheumatism and strengthening muscles and bones.Through multiple gel chromatography purifications,we obtained the deer bone protein(DBP)with a protein content of 76.43%,which was then analyzed using label-free proteomics.Subsequently,an adjuvant arthritis(AA)rat model was established.The ferroptosis pathway was chosen for study based on transcriptomic analysis of AA rat synovial tissue.The molecules with the best docking scores,Nrf2 and Keapl,were then visualized to confirm their validity.Additionally,results from electron microscopy observations,and Western blot(WB)experiments indicated that deer bone protein activates the ferroptosis signaling pathway,alleviating synovial hyperplasia.Therefore,regulating the Keapl/Nrf2 signaling pathway is key to promoting ferroptosis of deer bone protein to improve RA.This study provides new insights into the search for natural foods to improve RA and offers theoretical support for the full development and utilization of Sika deer resources and deer bone products.展开更多
BACKGROUND Chronic hepatitis B(CHB)is a significant global health issue,and interferon(IFN)is one of the main first-line therapies for CHB.AIM To investigate the altered transcriptome,metabolites,and their correlation...BACKGROUND Chronic hepatitis B(CHB)is a significant global health issue,and interferon(IFN)is one of the main first-line therapies for CHB.AIM To investigate the altered transcriptome,metabolites,and their correlations,as well as the effects and mechanisms of IFN treatment for CHB.METHODS The patients received peginterferon alfa-2b at a dose of 180μg for 0,1,3,and 6 months and serum samples were collected for clinical biological assays,transcriptomics,and metabolomics analyses.RESULTS The results showed that IFN-related immune pathways and neutrophil extracellular traps(NETs)were the most significantly altered pathways following IFN treatment.Correlation analysis revealed a strong link between immune system-related genes in the transcriptome and dipeptides in the metabolome during IFN-αtreatment.Notably,core components of NETs,including histones H2A clustered histone 14,H2B clustered histone 5,H3 clustered histone 1,and H4 clustered histone 4,were significantly increased after IFN treatment.The positively charged histones may bind to the negatively charged viral envelope,potentially enhancing the antiviral effect.CONCLUSION Integrated non-targeted transcriptomic and metabolomic analyses to CHB patients undergoing IFN-αtreatment revealed that IFN-related immune pathways and NETs were the most significantly affected pathways during IFN treatment.These findings provide a deeper understanding of the role of NETs and dipeptides in the antiviral response to IFN treatment for CHB.展开更多
Bone and skeletal muscle are essential components of musculoskeletal system,enabling movement,load-bearing,and systemic homeostasis.These tissues communicate through dynamic bone-muscle crosstalk mediated by cytokines...Bone and skeletal muscle are essential components of musculoskeletal system,enabling movement,load-bearing,and systemic homeostasis.These tissues communicate through dynamic bone-muscle crosstalk mediated by cytokines,growth factors,and extracellular-matrix(ECM)proteins.The spatial organization of these mediators is critical for maintaining tissue integrity,and its disruption contributes to diseases,such as osteoporosis,sarcopenia,and metabolic syndrome.Despite this importance,spatial transcriptomics(ST)studies of bone-muscle interactions remain limited.Here,we applied 10x Genomics Visium ST with computational tools,e.g.,SMART and CellChat,to deconvolute cell-type composition and characterize cell-cell communication networks and ligand-receptor(L-R)interactions in mouse femur and adjacent skeletal muscle.We identified eight major cell types(erythroid cells,endothelial cells,skeletal muscle cells,osteoblasts,myeloid cells,monocytes/macrophages,mesenchymal stem cells,and adipocytes)with distinct spatial transcriptional profiles and thirteen CellChat-inferred pathways,such as ECM-receptor related(e.g.,COLLAGEN,TENASCIN,THBS)and secreted-signaling involved(e.g.,VEGF)pathways.Representative L-R pairs include Col1a1/Col1a2-Sdc4,mediating osteoblast-to-muscle interactions,and Col4a1-Sdc4,facilitating muscle-to-osteoblast interactions in COLLAGEN,Tnxb-Sdc4 in TENASCIN,supporting muscle-to-osteoblast/muscle/myeloid/endothelial communication,Comp-Sdc4 in THBS,driving monocyte/macrophage-to-osteoblast/muscle signaling,and Vegfa-Vegfr1/Vegfr2 in VEGF,mediating muscle-toendothelial/myeloid signaling.Immunostaining validated colocalization of several representative L-R pairs with their corresponding cells.Additionally,independent mouse and human bone scRNA-seq datasets reproduced most of the pathways and L-R pairs identified in ST,underscoring the robustness and cross-species relevance of our findings.Together,we present an initial spatially resolved transcriptome-wide map of bone-muscle intercellular communication,providing novel insights into molecular crosstalk and establishing groundwork for future studies in musculoskeletal disorders.展开更多
Tomato(Solanum lycopersicum L.)is an herbaceous annual belonging to the genus Solanum in the family Solanaceae,native to South America.Protected cultivation has significantly increased annual tomato yields(Zhang et al...Tomato(Solanum lycopersicum L.)is an herbaceous annual belonging to the genus Solanum in the family Solanaceae,native to South America.Protected cultivation has significantly increased annual tomato yields(Zhang et al.,2024;Lou et al.,2025).Balancing quality and yield improvement has therefore become essential to meeting market needs(Gao et al.,2023).Numerous studies on protected tomato production highlight theeffectiveness of mulch cultivation(Dhaliwal et al.,2016).展开更多
Biological systems exhibit high complexity and heterogeneity:the maintenance of physiological homeostasis and the progression of disease in the human body are fundamentally driven by the discrete states,behaviors,and ...Biological systems exhibit high complexity and heterogeneity:the maintenance of physiological homeostasis and the progression of disease in the human body are fundamentally driven by the discrete states,behaviors,and interactions of billions of individual cells[1].展开更多
Methcathinone,a widely abused synthetic cathinone,poses a significant public health risk because of its severe neurotoxicity and high addictive potential.In this study,we used a zebrafish model to investigate the mech...Methcathinone,a widely abused synthetic cathinone,poses a significant public health risk because of its severe neurotoxicity and high addictive potential.In this study,we used a zebrafish model to investigate the mechanisms underlying its neurobehavioural effects.Methcathinone exposure reduced larval survival and induced a range of abnormal behaviours.Most notably,conditioned place preference(CPP)tests demonstrated the potent rewarding properties of methcathinone,as shown by a significant 22.2%increase in time spent in the drug-paired light zone compared with baseline(P<0.01).Transcriptomic analysis of brain tissue revealed systemic disruption of the neuroactive ligand-receptor interaction pathway.Gene set enrichment analysis(GSEA)further revealed significant suppression ofγ-aminobutyric acid(GABA)signalling(NES=-1.64,P<0.05)and glutamate receptor signalling,including ionotropic and AMPA receptor signalling(P<0.05).Quantitative PCR validation confirmed the marked downregulation of key genes involved in these pathways:the mRNA expression of GABAergic receptors(e.g.,gabra 1 and gabra 2),glutamatergic receptors(e.g.,gria 2 and grin2B),and the dopamine transporter slc6a3 decreased by 67.0%to 97.9%(all P<0.01).These results suggest that methcathinone drives reward-seeking behaviour through a synergistic dual-target mechanism;specifically,the concurrent suppression of GABAergic inhibition and slc6a3-mediated reuptake likely facilitates dopaminergic hyperactivity,whereas the downregulation of glutamate receptors reflects a homeostatic response to overstimulation.Our findings provide novel mechanistic insight into the development of methcathinone use disorder in humans.展开更多
Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,t...Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.展开更多
Background:Experimental animal models are essential for understanding the molecular mechanisms of human leukemia and testing potential therapies.Chemical induction using 7,12-dimethylbenz[a]anthracene(DMBA)has shown p...Background:Experimental animal models are essential for understanding the molecular mechanisms of human leukemia and testing potential therapies.Chemical induction using 7,12-dimethylbenz[a]anthracene(DMBA)has shown promise in recapitulating features of leukemogenesis in rodents,but its molecular fidelity to human disease remains underexplored.The aim of this study was to evaluate the transcriptomic landscape of a DMBA-induced leukemia rat model and assess its alignment with known gene expression signatures and oncogenic pathways in human leukemia.Methods:Male Wistar rats were treated with DMBA to induce leukemia.RNA was extracted from whole blood and subjected to RNA sequencing.Differentially expressed genes(DEG)were identified using RNA-seq by expectation-maximization and NOISeq.Functional enrichment analysis,Gene Ontology mapping,and protein interaction networks were analyzed via STRING.Prognostic relevance of key DEGs was explored using data from the Human Protein Atlas.Results:The DMBA-induced model showed significant upregulation of leukemiaassociated genes,including FLT3,NRAS,KRAS,ABL1,BCR,and NPM1.The top 10 upand downregulated genes were enriched in pathways related to cell fate,proliferation,apoptosis,and immune regulation.Particularly,genes such as MEIS2,CXCL9,and WIF1 were linked to hematopoietic dysregulation and poor prognosis in various cancers.Comparative analysis revealed strong transcriptomic overlap with human leukemia/carcinogenesis gene signatures,supporting the model's translational validity.Conclusion:In conclusion,the DMBA-induced leukemia rat model exhibits a transcriptomic profile that closely mirrors key oncogenic and prognostic features of human leukemia.This model holds significant promise for preclinical studies targeting leukemogenesis and therapeutic intervention strategies.展开更多
We read with interest the recent study by Zeber-Lubecka et al,published in the World Journal of Hepatology,investigating transcriptome profiles of peripheral blood mononuclear cells(PBMCs)in male adolescents with non-...We read with interest the recent study by Zeber-Lubecka et al,published in the World Journal of Hepatology,investigating transcriptome profiles of peripheral blood mononuclear cells(PBMCs)in male adolescents with non-alcoholic fatty liver disease(NAFLD).To maintain consistency with the original publication,we retain the term“NAFLD”throughout this commentary,while recognizing the recent shift toward the MASLD nomenclature.The authors stimulated PBMCs ex vivo with autologous fecal extracts to explore immune-microbiota interactions.Their results revealed distinct transcriptomic and cytokine patterns,including elevated pro-inflammatory mediators indicative of early immune dysregulation.These findings underscore the impact of host-specific gut microbiota on systemic immunity and suggest that PBMC-based immune signatures could serve as minimally invasive biomarkers.This work provides valuable insights into gutimmune crosstalk in pediatric NAFLD and offers a foundation for future research on early diagnosis and therapeutic strategies.展开更多
This article presents a Hierarchical Pathway-Masked Attention Autoencoder(H-PAAE),a biologically inspired representation-learning framework that enables explainable AI-guided cancer diagnosis.The model directly integr...This article presents a Hierarchical Pathway-Masked Attention Autoencoder(H-PAAE),a biologically inspired representation-learning framework that enables explainable AI-guided cancer diagnosis.The model directly integrates the curated MSigDB Hallmark pathways,introducing pathway-constrained information flow and mechanistic interpretability through multi-level attention mechanisms.Based on TCGA RNA-seq data from 33 tumor types,H-PAAE compresses approximately 20,000 genes into a 128-dimensional latent space while preserving biologically meaningful structure.When used with XGBoost classification,H-PAAE delivers 92.37%test accuracy and 99.38%macro-AUROC with robust cross-validation results(92.5±0.6%).SHAP analysis identifies a small number of key latent features,corresponding to conserved oncogenic processes,and pathway enrichment analysis shows strong overlap with cancer hallmarks.H-PAAE provides a clear and interpretable biological foundation for pan-cancer classification,with well-calibrated posterior probabilities that can be used for clinical decision-making,and can be easily integrated into multimodal diagnostic workflows.展开更多
Objective:Exposure to extreme cold temperatures may increase the risk of cardiovascular diseases.This study aimed to investigate the effects of cold exposure on the heart and its underlying mechanisms using an integra...Objective:Exposure to extreme cold temperatures may increase the risk of cardiovascular diseases.This study aimed to investigate the effects of cold exposure on the heart and its underlying mechanisms using an integrated transcriptomic and metabolomic approach.Methods:C57BL/6 mice were subjected to cold exposure at 4°C for 12 hours per day for 4 weeks.Transcriptomics and metabolomics profiles of the heart were analyzed.Differentially expressed genes(DEGs)and differentially expressed metabolites(DEMs)were identified,and mRNA expression levels were validated by qRT-PCR.Enrichment analyses were performed to identify significantly affected pathways.Transcriptomic and metabolomic data were then integrated to provide a comprehensive view of molecular alterations induced by cold exposure.To further evaluate the relationship between cold exposure and cardiovascular diseases,a myocardial infarction(MI)mouse model was established,and overlapping genes between cold exposure and MI were analyzed.Results:Cold exposure significantly altered both the transcriptomic and metabolomic profiles of mouse hearts.Pathway enrichment analyses based on DEGs and DEMs identified several signaling pathways affected by cold stress.Integrated transcriptomic and metabolomic analyses further highlighted potential metabolic and signaling pathways associated with cold exposure.By cross-referencing DEGs associated with cold exposure with those from the MI model in the GEO database(GSE223208),34 overlapping genes were identified.Integrated analyses implicated key genes(Tnfrsf12a and Nppb)in cold-aggravated cardiac remodeling,which were further validated in MI models.Conclusion:Cold exposure reprograms the cardiac transcriptome and metabolome in mice.Cold exposure and MI share a subset of DEGs,which may help illuminate the pathophysiological interplay between cold stress and MI,highlighting potential therapeutic targets for cold-exacerbated cardiovascular diseases.展开更多
Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms o...Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82404892(to QY),82061160374(to ZZ)the Science and Technology Development Fund,Macao Special Administrative Region,China,Nos.0023/2020/AFJ,0035/2020/AGJ+2 种基金the University of Macao Research Grant,Nos.MYRG2022-00248-ICMS,MYRG-CRG2022-00010-ICMS(to MPMH)the Natural Science Foundation of Guangdong Province,No.2024A1515012818(to ZZ)the Fundamental Research Funds for the Central Universities,No.21623114(to ZZ).
摘要Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.
基金Supported by the National Key R&D Program of China(No.2022YFC2804600)the National Natural Science Foundation of China(No.42006096)+1 种基金the Doctoral Start-Up Fund of Qingdao Agricultural University(No.663-1117004)the Horizontal Project:Development of Antarctic Krill Feed for Turbot and Research on Nutrition and Disease Resistance(No.H20220193)。
摘要The sedimentary ecosystems of deep-sea floors harbor abundant biological resources,with fungi emerging as predominant eukaryotic taxa that perform crucial ecological roles.However,the adaptive strategies enabling fungal survival in these extreme low-oxygen environments remain poorly understood.We elucidated the hypoxic adaptation mechanisms of Chaetomium globosum YP-106,an oxygen-sensitive fungus isolated from 6215-m deep seawater in Yap Trench in the western Pacific.Under hypoxic conditions,the strain growth rate was reduced with significant mycelial morphological alterations.Multi-omics analyses revealed 313 differentially abundant metabolites(DAMs)and 661 differential expression genes(DEGs),enriched in mainly fatty acid metabolism(degradation/synthesis)and carbohydrate utilization pathways.It is noteworthy that gene ontology(GO)enrichment analysis identified 171 membrane-associated genes,suggesting that structural membrane remodeling may serve as a key adaptive strategy.Integrated pathway analysis demonstrated metabolic reprogramming characterized by suppressed tricarboxylic acid(TCA)cycle activity and preferential activation of anaerobic glycolysis for ATP production.Importantly,the NADH dehydrogenase-mediated NAD+regeneration was enhanced as a compensatory mechanism sustaining residual TCA cycle function.These findings elucidated hypoxic metabolic mechanisms in deep-sea ascomycetes,enhanced our understanding of microbial energy conservation strategies in oxygen-deprived environments,and offered novel perspectives on eukaryotic extremophile adaptation mechanisms in benthic ecosystems.
基金supported by the General Scientific Research Project of the Zhejiang Education Department,China(Grant No.Y202249221).
摘要Ustiloxins are the primary secondary metabolites of Ustilaginoidea virens(teleomorph:Villosiclava virens).While these toxins are known to exhibit toxicity in certain animals,their potential risks to human health require further investigation.Therefore,this study was conducted using male mice as experimental animal to explore their potential health risks.We observed morphological changes in cells and structural lesions in mitochondria using electron microscopy,combined with Hematoxylin and Eosin(H&E)staining.We utilized transcriptomics,proteomics,and bioinformatics techniques to analyze the regulatory networks associated with ustiloxins in the context of liver damage and study the mechanism of liver injury caused by ustiloxins in mice.Differentially expressed genes(DEGs)were linked to terms such as‘metabolism of exogenous substances with cytochrome P450’,‘peroxisomes’,and‘negative regulation of the inflammatory response’.Western blotting and quantitative real-time PCR(qRT-PCR)demonstrated that ustiloxins can further activate the inflammatory pathways of Nrf2/HO-1 and NLRP3 by activating cytochrome P450(CYP450),leading to liver damage in mice.
基金supported by the National Natural Science Foundation of China(Grant No.32270133)the Yunnan Revitalization Talent Project,China(Grant Nos.XDYC-QNRC-2023-0672 and XDYCCYCX-2022-0026)+4 种基金the Yunnan Applied Basic Research,China(Grant No.202301AT070329)the Major Science and Technology Project in Yunnan,China(Grant No.202402AE090026)the West Light Foundation of Chinese Academy of Sciences(CAS)the 14th Five-Year Plan of Xishuangbanna Tropical Botanical Garden,CASthe Yunnan Province Key Research and Development Plan Project,China(Grant Nos.202303AM140023 and 202403AM140005)。
摘要Drought severely affects sustainable agricultural production worldwide.Upland rice ecotypes perform favorably under drought conditions;however,the underlying mechanisms remain largely unclear.In this study,we investigated changes in the transcriptome,metabolome,and physio-biochemical attributes of rice subjected to drought and supplemented with nitric oxide(NO)and hydrogen sulfide(H2S).Drought stress reduced growth and triggered lipid peroxidation;however,NO and H2S application alleviated the growth decline and lipid peroxidation.In addition,NO and H2S upregulated the activity of antioxidant enzymes,thereby mitigating the drought-induced oxidative stress.
基金supported by the Postdoctoral Research Program Support of Anhui Province, China (2024C863)the China Agriculture Research System of MOF and MARA (CARS-23-G40, CARS-23-G49)the Youth Development Fund from Anhui Academy of Agricultural Science, China (QNYC-202121)。
摘要Anthocyanins play a crucial role in plant growth,development,reproduction,and stress response.Additionally,anthocyanins enhance the quality of fruits and vegetables due to their antioxidant properties.While numerous previous studies have been conducted on anthocyanins,limited information exists regarding their composition and the role of the anthocyanin pathway gene dihydroflavonol 4-reductase(DFR) in chili pepper leaves.In this study,we used a purple leaf pepper cultivar H18 in which the anthocyanin content in leaves decreases with plant growth and development.Targeted anthocyanin metabolite assays revealed that the contents of delphinidin,malvidin,and petunidin derivatives followed the same trend as the overall anthocyanin content,with delphinidin derivatives being the predominant component of H18pepper leaves.Transcriptome sequencing was performed on H18 leaves at four different stages.The results showed that differentially expressed genes(DEGs) at various stages were primarily associated with biological processes and flavonoid metabolic pathways.Through phylogenetic tree and expression analysis,we identified three candidate genes involved in DFR function.Substrate catalysis assays of CaDFRs demonstrated that only CaDFR1 was active,catalyzing dihydroquercetin(DHQ),dihydromyricetin(DHM),and dihydrokaempferol(DHK).VIGS-mediated silencing of CaDFR1resulted in a significant decrease in anthocyanin levels in H18 pepper leaves and stems,along with a reduction in the expression levels of other candidate functional genes in the anthocyanin metabolic pathway.This study identifies the key anthocyanin components in the leaves of H18 peppers and validates the function of CaDFR1,providing a theoretical foundation for modifying anthocyanin content in pepper plants through molecular breeding.
基金supported by the Hainan Excellent Talent Team and the Basic Research Project in 2023 of Yazhouwan National Laboratory.
摘要Salinization affects over 800 million hectares of irrigated land globally.As a typical salt-sensitive crop,rice(Oryza sativa L.)suffers from high ionic stress,elevated osmotic pressure,and excessive accumulation of reactive oxygen species(ROS)in saline soils,resulting in growth inhibition(Goyal et al.,2021;Jia et al.,2022).Salt tolerance in rice involves complex mechanisms across morphological,physiological,and molecular levels(Zhu,2016;Alkahtani and Dwiningsih,2023;Li et al.,2024).
基金funded by the Project of National Key Research and Development Program of China(2022YFD2101001)the Project of National Natural Science Foundation of China(32172226)+4 种基金China Agriculture Research System(CARS-40-K25CARS-40-S11)the Special Fund for Anhui Agriculture Research System(AHCYJSTX-NCPJG)-15the Project of Key Laboratory for Animal Food Green Manufacturing and Resource Ming of Anhui Province(PA2023GDSK0125)the Cooperative Project of Hefei University of Technology-Anhui Rongda Food Co.,Ltd.(W2020JSKF0489).
摘要Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on repairing skeletal muscle injuries has been rarely reported.In this study,a mouse model of muscle injury was constructed and found that OVA significantly increased muscle weight,muscle thickness,and exercise capacity in muscle-injured mice.Meanwhile,OVA improved the morphology of muscle tissues by reducing serum levels of urea nitrogen,creatine kinase,and lactate dehydrogenase,as well as decreasing the levels of inflammatory factors interleukin(IL)-1β,tumor necrosis factor α,and IL-6,respectively.In addition,transcriptomic and metabolomic analyses revealed that OVA could enhance muscle tissue morphology by upregulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and improving amino acid metabolism through the upregulation of Col11a2,Ccn2,Thbs1,Tnc,Klf2,Bcl2l1,Adh3a1,and Rsad1.The study provided a theoretical foundation for understanding the molecular mechanisms in OVA-aided muscle injury repair.
基金supported by grants from Chi Mei Medical Center(CMFJ11003,CMFJ11205,CMNCKU 11303)Chi Mei Medical Center,Liouying(CLFHR 11106,CLFHR11305).
摘要Background:Partial epithelial-mesenchymal transition(p-EMT)is a dynamic cellular state associated with metastasis and adverse outcomes in multiple cancers,but its prognostic significance in ovarian cancer remains unclear.This study aimed to develop and validate an ovarian cancer-specific transcriptomic signature based on p-EMT-related genes,and to determine whether this signature can improve prognostic stratification and overall survival prediction across independent cohorts.Methods:A pan-cancer p-EMT gene set was curated from ten published studies.Using transcriptomic and clinical data from TCGA-OV(n=488),a six-gene p-EMT signature was developed via LASSO regression to generate a patient-specific risk score.The score was integrated with clinical variables to construct a prognostic nomogram and validated in the external GEO cohort GSE140082(n=380)and GSE165808(n=51).Results:A six-gene p-EMT transcriptomic signature(ADAM9,ANXA8L1,FSTL3,RABAC1,TPM4,and TWIST1)was significantly associated with overall survival(OS)and stratified patients into high-and low-risk groups(adjusted HR=1.74,p<0.001).Incorporation with age and FIGO stage in a nomogram improved predictive performance,with AUCs of 0.727,0.700,and 0.656 at 1-,3-,and 5-year OS,respectively.External validation in GSE140082 and GSE165808 confirmed model robustness,yielding 3-year AUCs of 0.630 and 0.826,respectively,demonstrating preserved prognostic value across independent cohorts and disease stages.Conclusions:This six-gene p-EMT transcriptomic signature demonstrates prognostic value in ovarian cancer and offers potential for individualized risk stratification and clinical decisionsupport.
基金supported by funding from the Major Science and Technology Projects in Jilin Province(20220304001YY,20220304003YY).
摘要Rheumatoid arthritis(RA)is a common long-term autoimmune disease that causes synovial tissue to grow and behave like a tumor when inflammatory factors are present.This can cause joint pain,muscle loss,and other serious problems.Therefore,finding natural anti-RA products and effective treatment strategies is crucial for achieving good prognoses in RA patients.The deer bone is rich in protein,which has the effect of eliminating rheumatism and strengthening muscles and bones.Through multiple gel chromatography purifications,we obtained the deer bone protein(DBP)with a protein content of 76.43%,which was then analyzed using label-free proteomics.Subsequently,an adjuvant arthritis(AA)rat model was established.The ferroptosis pathway was chosen for study based on transcriptomic analysis of AA rat synovial tissue.The molecules with the best docking scores,Nrf2 and Keapl,were then visualized to confirm their validity.Additionally,results from electron microscopy observations,and Western blot(WB)experiments indicated that deer bone protein activates the ferroptosis signaling pathway,alleviating synovial hyperplasia.Therefore,regulating the Keapl/Nrf2 signaling pathway is key to promoting ferroptosis of deer bone protein to improve RA.This study provides new insights into the search for natural foods to improve RA and offers theoretical support for the full development and utilization of Sika deer resources and deer bone products.
摘要BACKGROUND Chronic hepatitis B(CHB)is a significant global health issue,and interferon(IFN)is one of the main first-line therapies for CHB.AIM To investigate the altered transcriptome,metabolites,and their correlations,as well as the effects and mechanisms of IFN treatment for CHB.METHODS The patients received peginterferon alfa-2b at a dose of 180μg for 0,1,3,and 6 months and serum samples were collected for clinical biological assays,transcriptomics,and metabolomics analyses.RESULTS The results showed that IFN-related immune pathways and neutrophil extracellular traps(NETs)were the most significantly altered pathways following IFN treatment.Correlation analysis revealed a strong link between immune system-related genes in the transcriptome and dipeptides in the metabolome during IFN-αtreatment.Notably,core components of NETs,including histones H2A clustered histone 14,H2B clustered histone 5,H3 clustered histone 1,and H4 clustered histone 4,were significantly increased after IFN treatment.The positively charged histones may bind to the negatively charged viral envelope,potentially enhancing the antiviral effect.CONCLUSION Integrated non-targeted transcriptomic and metabolomic analyses to CHB patients undergoing IFN-αtreatment revealed that IFN-related immune pathways and NETs were the most significantly affected pathways during IFN treatment.These findings provide a deeper understanding of the role of NETs and dipeptides in the antiviral response to IFN treatment for CHB.
基金supported or benefited by grants from the National Institutes of Health[U19AG055373,P20GM109036,R01AR069055,and R01AG061917].
摘要Bone and skeletal muscle are essential components of musculoskeletal system,enabling movement,load-bearing,and systemic homeostasis.These tissues communicate through dynamic bone-muscle crosstalk mediated by cytokines,growth factors,and extracellular-matrix(ECM)proteins.The spatial organization of these mediators is critical for maintaining tissue integrity,and its disruption contributes to diseases,such as osteoporosis,sarcopenia,and metabolic syndrome.Despite this importance,spatial transcriptomics(ST)studies of bone-muscle interactions remain limited.Here,we applied 10x Genomics Visium ST with computational tools,e.g.,SMART and CellChat,to deconvolute cell-type composition and characterize cell-cell communication networks and ligand-receptor(L-R)interactions in mouse femur and adjacent skeletal muscle.We identified eight major cell types(erythroid cells,endothelial cells,skeletal muscle cells,osteoblasts,myeloid cells,monocytes/macrophages,mesenchymal stem cells,and adipocytes)with distinct spatial transcriptional profiles and thirteen CellChat-inferred pathways,such as ECM-receptor related(e.g.,COLLAGEN,TENASCIN,THBS)and secreted-signaling involved(e.g.,VEGF)pathways.Representative L-R pairs include Col1a1/Col1a2-Sdc4,mediating osteoblast-to-muscle interactions,and Col4a1-Sdc4,facilitating muscle-to-osteoblast interactions in COLLAGEN,Tnxb-Sdc4 in TENASCIN,supporting muscle-to-osteoblast/muscle/myeloid/endothelial communication,Comp-Sdc4 in THBS,driving monocyte/macrophage-to-osteoblast/muscle signaling,and Vegfa-Vegfr1/Vegfr2 in VEGF,mediating muscle-toendothelial/myeloid signaling.Immunostaining validated colocalization of several representative L-R pairs with their corresponding cells.Additionally,independent mouse and human bone scRNA-seq datasets reproduced most of the pathways and L-R pairs identified in ST,underscoring the robustness and cross-species relevance of our findings.Together,we present an initial spatially resolved transcriptome-wide map of bone-muscle intercellular communication,providing novel insights into molecular crosstalk and establishing groundwork for future studies in musculoskeletal disorders.
基金supported by the earmarked fund for National Natural Science Foundation of China(Grant No.32372793)Beijing Rural Revitalization Agricultural Science and Technology Project(Grant No.NY2502120425)+4 种基金The Ningxia Hui Autonomous Region key Research and Development Program project(Grant No.2023BCF01046)Earmarked Fund for Modern Agro-industry Technology Research System(Grant Nos.CARS-24-B04CARS-23-B05)The Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(Grant No.CAASASTIP-IVFCAAS)provided by the Key Laboratory of Biology and Genetic Improvement of Horticultural Crops(Vegetables),Ministry of Agriculture and Rural Affairs,China。
摘要Tomato(Solanum lycopersicum L.)is an herbaceous annual belonging to the genus Solanum in the family Solanaceae,native to South America.Protected cultivation has significantly increased annual tomato yields(Zhang et al.,2024;Lou et al.,2025).Balancing quality and yield improvement has therefore become essential to meeting market needs(Gao et al.,2023).Numerous studies on protected tomato production highlight theeffectiveness of mulch cultivation(Dhaliwal et al.,2016).
摘要Biological systems exhibit high complexity and heterogeneity:the maintenance of physiological homeostasis and the progression of disease in the human body are fundamentally driven by the discrete states,behaviors,and interactions of billions of individual cells[1].
基金Supported by the Natural Science Foundation of Zhejiang Province(No.LTGY23H230001,LGF19H280003)。
摘要Methcathinone,a widely abused synthetic cathinone,poses a significant public health risk because of its severe neurotoxicity and high addictive potential.In this study,we used a zebrafish model to investigate the mechanisms underlying its neurobehavioural effects.Methcathinone exposure reduced larval survival and induced a range of abnormal behaviours.Most notably,conditioned place preference(CPP)tests demonstrated the potent rewarding properties of methcathinone,as shown by a significant 22.2%increase in time spent in the drug-paired light zone compared with baseline(P<0.01).Transcriptomic analysis of brain tissue revealed systemic disruption of the neuroactive ligand-receptor interaction pathway.Gene set enrichment analysis(GSEA)further revealed significant suppression ofγ-aminobutyric acid(GABA)signalling(NES=-1.64,P<0.05)and glutamate receptor signalling,including ionotropic and AMPA receptor signalling(P<0.05).Quantitative PCR validation confirmed the marked downregulation of key genes involved in these pathways:the mRNA expression of GABAergic receptors(e.g.,gabra 1 and gabra 2),glutamatergic receptors(e.g.,gria 2 and grin2B),and the dopamine transporter slc6a3 decreased by 67.0%to 97.9%(all P<0.01).These results suggest that methcathinone drives reward-seeking behaviour through a synergistic dual-target mechanism;specifically,the concurrent suppression of GABAergic inhibition and slc6a3-mediated reuptake likely facilitates dopaminergic hyperactivity,whereas the downregulation of glutamate receptors reflects a homeostatic response to overstimulation.Our findings provide novel mechanistic insight into the development of methcathinone use disorder in humans.
基金the National Natural Science Foundation of China(82204935)the construction project of Zhao Feng National Old Pharmacist Inheritance Studio of State Administration of Traditional Chinese Medicine(National Traditional Chinese Medicine Education Letter[2024]255)+1 种基金the open project of the Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine in Shaanxi Province(KF202302)the project of Xi’an Municipal Bureau of Science and Technology(23YXYJ0042)for financial support.
摘要Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.
基金Deanship of Scientific Research at Imam Abdulrahman Bin Faisal University,Grant/Award Number:CAMS-099-2017。
摘要Background:Experimental animal models are essential for understanding the molecular mechanisms of human leukemia and testing potential therapies.Chemical induction using 7,12-dimethylbenz[a]anthracene(DMBA)has shown promise in recapitulating features of leukemogenesis in rodents,but its molecular fidelity to human disease remains underexplored.The aim of this study was to evaluate the transcriptomic landscape of a DMBA-induced leukemia rat model and assess its alignment with known gene expression signatures and oncogenic pathways in human leukemia.Methods:Male Wistar rats were treated with DMBA to induce leukemia.RNA was extracted from whole blood and subjected to RNA sequencing.Differentially expressed genes(DEG)were identified using RNA-seq by expectation-maximization and NOISeq.Functional enrichment analysis,Gene Ontology mapping,and protein interaction networks were analyzed via STRING.Prognostic relevance of key DEGs was explored using data from the Human Protein Atlas.Results:The DMBA-induced model showed significant upregulation of leukemiaassociated genes,including FLT3,NRAS,KRAS,ABL1,BCR,and NPM1.The top 10 upand downregulated genes were enriched in pathways related to cell fate,proliferation,apoptosis,and immune regulation.Particularly,genes such as MEIS2,CXCL9,and WIF1 were linked to hematopoietic dysregulation and poor prognosis in various cancers.Comparative analysis revealed strong transcriptomic overlap with human leukemia/carcinogenesis gene signatures,supporting the model's translational validity.Conclusion:In conclusion,the DMBA-induced leukemia rat model exhibits a transcriptomic profile that closely mirrors key oncogenic and prognostic features of human leukemia.This model holds significant promise for preclinical studies targeting leukemogenesis and therapeutic intervention strategies.
摘要We read with interest the recent study by Zeber-Lubecka et al,published in the World Journal of Hepatology,investigating transcriptome profiles of peripheral blood mononuclear cells(PBMCs)in male adolescents with non-alcoholic fatty liver disease(NAFLD).To maintain consistency with the original publication,we retain the term“NAFLD”throughout this commentary,while recognizing the recent shift toward the MASLD nomenclature.The authors stimulated PBMCs ex vivo with autologous fecal extracts to explore immune-microbiota interactions.Their results revealed distinct transcriptomic and cytokine patterns,including elevated pro-inflammatory mediators indicative of early immune dysregulation.These findings underscore the impact of host-specific gut microbiota on systemic immunity and suggest that PBMC-based immune signatures could serve as minimally invasive biomarkers.This work provides valuable insights into gutimmune crosstalk in pediatric NAFLD and offers a foundation for future research on early diagnosis and therapeutic strategies.
基金by the Deanship of Graduate Studies and Scientific Research at Jouf University under grant No.DGSSR-2025-FC-01029.
摘要This article presents a Hierarchical Pathway-Masked Attention Autoencoder(H-PAAE),a biologically inspired representation-learning framework that enables explainable AI-guided cancer diagnosis.The model directly integrates the curated MSigDB Hallmark pathways,introducing pathway-constrained information flow and mechanistic interpretability through multi-level attention mechanisms.Based on TCGA RNA-seq data from 33 tumor types,H-PAAE compresses approximately 20,000 genes into a 128-dimensional latent space while preserving biologically meaningful structure.When used with XGBoost classification,H-PAAE delivers 92.37%test accuracy and 99.38%macro-AUROC with robust cross-validation results(92.5±0.6%).SHAP analysis identifies a small number of key latent features,corresponding to conserved oncogenic processes,and pathway enrichment analysis shows strong overlap with cancer hallmarks.H-PAAE provides a clear and interpretable biological foundation for pan-cancer classification,with well-calibrated posterior probabilities that can be used for clinical decision-making,and can be easily integrated into multimodal diagnostic workflows.
基金supported by the National Natural Science Foundation of China(Grant No.82370269)。
摘要Objective:Exposure to extreme cold temperatures may increase the risk of cardiovascular diseases.This study aimed to investigate the effects of cold exposure on the heart and its underlying mechanisms using an integrated transcriptomic and metabolomic approach.Methods:C57BL/6 mice were subjected to cold exposure at 4°C for 12 hours per day for 4 weeks.Transcriptomics and metabolomics profiles of the heart were analyzed.Differentially expressed genes(DEGs)and differentially expressed metabolites(DEMs)were identified,and mRNA expression levels were validated by qRT-PCR.Enrichment analyses were performed to identify significantly affected pathways.Transcriptomic and metabolomic data were then integrated to provide a comprehensive view of molecular alterations induced by cold exposure.To further evaluate the relationship between cold exposure and cardiovascular diseases,a myocardial infarction(MI)mouse model was established,and overlapping genes between cold exposure and MI were analyzed.Results:Cold exposure significantly altered both the transcriptomic and metabolomic profiles of mouse hearts.Pathway enrichment analyses based on DEGs and DEMs identified several signaling pathways affected by cold stress.Integrated transcriptomic and metabolomic analyses further highlighted potential metabolic and signaling pathways associated with cold exposure.By cross-referencing DEGs associated with cold exposure with those from the MI model in the GEO database(GSE223208),34 overlapping genes were identified.Integrated analyses implicated key genes(Tnfrsf12a and Nppb)in cold-aggravated cardiac remodeling,which were further validated in MI models.Conclusion:Cold exposure reprograms the cardiac transcriptome and metabolome in mice.Cold exposure and MI share a subset of DEGs,which may help illuminate the pathophysiological interplay between cold stress and MI,highlighting potential therapeutic targets for cold-exacerbated cardiovascular diseases.
基金supported by the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
摘要Ischemic stroke remains a leading cause of disability and death,with mesenchymal stem cell-derived exosomes emerging as a promising therapeutic avenue.However,the optimal timing and underlying therapeutic mechanisms of exosome treatment require further elucidation.In this study,we used a murine model of middle cerebral artery occlusion to investigate the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes administered intravenously at an early(6 hours)or delayed(3 days)time point post-ischemia.Compared with delayed treatment,early administration of exosomes resulted in significantly superior efficacy,as evidenced by improved neurological function scores and reduced infarct volumes.Transcriptomic analysis of brain tissues from mice receiving early exosome treatment revealed marked downregulation of inflammation-related genes,including Ccl2,Ccl5,Cxcl10,Il-1β,Il-6,Itgam,Itgax,and Tnf-α.Metabolomic profiling of these brain tissues further identified modulation of key metabolites,including trimethylamine N-oxide,glutathione,1-stearoyl-rac-glycerol,and phosphatidylcholine,suggesting that alteration of metabolic pathways contributes to the therapeutic effect.Integrated transcriptomic and metabolomic analysis pinpointed significant modulation of pathways involving metabolism of eicosapentaenoic acid,lysine,propanoate,and tyrosine.These findings suggest that umbilical cord mesenchymal stem cell-derived exosomes,particularly when administered early post-ischemia,exert their neuroprotective effects by broadly suppressing inflammatory pathways and modulating key metabolic processes in the ischemic brain,highlighting their potential as a therapeutic intervention for ischemic stroke.