Rui Chena,b,Tangbing Cui a,b,∗a School of Biology and Biological Engineering,South China University of Technology,Guangzhou 510006,China b Guangdong Key Laboratory of Fermentation and Enzyme Engineering,South China Un...Rui Chena,b,Tangbing Cui a,b,∗a School of Biology and Biological Engineering,South China University of Technology,Guangzhou 510006,China b Guangdong Key Laboratory of Fermentation and Enzyme Engineering,South China University of Technology,Guangzhou 510006,China The authors regret that the published version of this article contained several errors and omissions,which are described and corrected below.1.Figs.3 and 4(figure order and legends).In the published article,Figs.3 and 4 were inadvertently published in reversed order.The figures should be swapped so that the figure content matches its caption.The correct figures and their legends are provided on the following page.2.Title correction.The compound name in the published title was incorrectly typeset as“benzo[a]pyrene”The correct spelling is“benzo[a]pyrene.”3.Text corrections in Section 2.4.Several typographical errors occurred in Section 2.4(“Up-regulation of acetoin,lactate,and kanosamine biosynthesis under sodium gluconate treatment”).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
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
As a specific spoilage organism of seafood under refrigerated temperature conditions,Shewanella spp.tend to form biofilms that exacerbate the occurrence of seafood spoilage.Biofilm-promoting factor A(BpfA)has been rep...As a specific spoilage organism of seafood under refrigerated temperature conditions,Shewanella spp.tend to form biofilms that exacerbate the occurrence of seafood spoilage.Biofilm-promoting factor A(BpfA)has been reported to promote the adhesion and biofilm formation of Shewanella spp.,but its role in adhesion and biofilm formation of S.putrefaciens under cold stress needs to be further investigated.To better comprehend the effect of BpfA on adhesion and biofilm formation of S.putrefaciens under cold stress(4℃),bacterial adhesion and biofilm phenotype of S.putrefaciens CN32 WT andΔbpfA at 4℃were analyzed and performed transcriptomics.The results showed that the deletion of bpfA had almost no effect on the growth of S.putrefaciens CN32 at 4℃,but weakened the unicellular adhesion capacity of S.putrefaciens CN32 and destabilized the stability of the multicellular adhesion layer.In addition,the biomass of the mature biofilm formed byΔbpfA was merely around 50%of that observed in the mature biofilm of S.putrefaciens CN32 WT,the average thickness and volume of the biofilm decreased by 18%and 27%,respectively,and the composition of the biofilm changed.Transcriptome analysis demonstrated that the deletion of bpfA led to differential expression of genes involved in metabolic pathways such as bacterial chemotaxis,two-component system,tyrosine metabolism,drug metabolism-other enzymes and biofilm formation-Vibrio cholerae,which in turn influenced bacterial adhesion and biofilm formation.Those results advance our acknowledgment of the character of BpfA on adhesion and biofilm formation of S.putrefaciens CN32,which contributes to understanding bacterial adhesion and the control of biofilm formation.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
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
Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the developmen...Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke.Here,we used a multi-omics approach combining single-cell and bulk transcriptomics.CellChat analysis revealed intercellular communication networks,while key genes were identified and predictive models built through Lasso regression.Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis.Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes.MicroRNA networks and transcription factors were investigated using mircode and RcisTarget.Experimental validation was performed using oxygen-glucose deprivation and transient middle cerebral artery occlusion models,focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function.We observed significantly elevated monocyte content in stroke brain tissue samples,and identified key monocyte genes associated with immune inflammation,chemokine signaling,and cell receptor function.A robust seven-gene predictive model for ischemic stroke was developed.CD274 strongly correlated with these seven genes,suggesting a potential immunomodulatory axis.In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes.In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen-glucose deprivation while reducing reactive oxygen species generation.In conclusion,this study maps post-stroke monocyte communication networks,identifies key signaling pathways,identifies regulatory mechanisms,and validates the functional importance of key genes,particularly abhydrolase domain-containing protein 2.These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.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
Microwave thermochemotherapy(MTC)has been applied to treat lip squamous cell carcinoma(LSCC),but a deeper understanding of its therapeutic mechanisms and molecular biology is needed.To address this,we used single-cell...Microwave thermochemotherapy(MTC)has been applied to treat lip squamous cell carcinoma(LSCC),but a deeper understanding of its therapeutic mechanisms and molecular biology is needed.To address this,we used single-cell transcriptomics(scRNA-seq)and spatial transcriptomics(ST)to highlight the pivotal role of tumor-associated neutrophils(TANs)among tumor-infiltrating immune cells and their therapeutic response to MTC.MNDA+TANs with anti-tumor activity(N1-phenotype)are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion,and these TANs are characterized by enhanced cytotoxicity,ameliorated hypoxia,and upregulated IL1B,activating T&NK cells and fibroblasts via IL1B-IL1R.In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC,fibroblasts accumulated in the tumor front(TF)can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs(pro-tumor phenotype)via CXCL12-CXCR4,which results in the aggregation of N1-TANs and extracellular matrix(ECM)deposition.In addition,we construct an N1-TANs marker,MX2,which positively correlates with better prognosis in LSCC patients,and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin(H&E)-stained images so as to conveniently guide decision making in clinical practice.Collectively,our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.展开更多
Malolactic fermentation,started by lactic acid bacteria,plays a crucial role in the production of high-quality wines.As global warming increases the ethanol content in wines,the success of malolactic fermentation depe...Malolactic fermentation,started by lactic acid bacteria,plays a crucial role in the production of high-quality wines.As global warming increases the ethanol content in wines,the success of malolactic fermentation depends on selecting ethanol-tolerant strains,especially for wines from increasingly warm climates.Lentilactobacillus hilgardii Q19 was isolated and characterized as an indigenous malolactic bacterium with higher ethanol tolerance properties.In this study,it was indicated that ethanol stress had significant effects on ATPase activity,antioxidant system,and cell membrane of L.hilgardii Q19 by measuring the physiological indicators under stress which include H^(+)-ATPase,Na^(+)/K^(+)-ATPase,Ca^(2+)/Mg^(2+)-ATPase activity,glutathione content,superoxide dismutase(SOD)activity and intracellular reactive oxygen species(ROS)content.The main metabolic pathways involved in ethanol stress such as ATP-binding cassette(ABC)transporters,pentose phosphate pathway,phosphotransferase system,glutathione metabolic pathway and two-component systems were screened by transcriptome sequencing analysis.The functions of the pentose phosphate pathway,pyruvate metabolic pathway and glycerolipid metabolism under ethanol stress were verified by constructing the L.hilgardii Q19 ethanol stress related key genes gnt K,pyk,and glp K overexpression vectors.The above findings may contribute to our understanding of the metabolic pathways and regulatory mechanisms of L.hilgardii Q19 in response to ethanol stress.展开更多
Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is...Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.展开更多
Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dyna...Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dynamic transcription of bovine germ cell population.Results In this study,we used Stereo-seq to construct a spatial transcription map of bovine testicular tissue at two ages.Four germ cell groups and five somatic cell groups were determined,and functional enrichment characterized their different biological functions and the differences between calves and adult bulls.At the same time,we also defined the subpopulations of cells and marker genes,then,clarified the communications between germ cells.Conclusion Our study constructed a spatial transcription map of bovine testicular tissue for the first time,and systematically described the dynamic transcription changes during spermatogenesis.These data laid the foundation for the study of spermatogenesis in large mammals and elucidated the transcriptional dynamics underlying male germ cell development.展开更多
Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underl...Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underlying the high anthocyanin accumulation during the fruit development and colouration of rabbiteye blueberry fruit,have not yet been fully clarified so far.The fruit anthocyanin content of rabbiteye blueberry in the karstic area of Guizhou Province,China,is much higher compared to that in other regions,and the fruit colour is highly affected by anthocyanin accumulation.Currently,the untargeted metabolomics and HPLC assays have been carried out using rabbiteye blueberry fruit at various stages,and it was investigated that cyanidin(Cy)and pelargonidin(Pg)reached their peaks at the red fruit(RF)stage,whereas delphinidin(Dp),petudinin(Pt),malvidin(Mv),and peonidin(Pn)got their ceilings at the mature fruit(MF)stage.Transcriptome and co-expression network analyses showed that 27 differentially expressed genes(DEGs)were associated with anthocyanin content,among which VdMYB56,belonging to the R2R3-MYB family,was markedly up-regulated during the development and colouration of fruit,and was significantly higher in the skin than in the pulp.Furthermore,VdMYB56-overexpressing tomato fruits demonstrated a substantial elevation in anthocyanin content on the 35th day after flowering(DAF).It was worth noting that VdMYB56 could directly bind to the promoter of Vd3GT to enhance its expression,thereby further strengthening the anthocyanin accumulation.Meantime,multiple assays verified that VdMYB69,an R2R3-MYB member,might interact with VdMYB56,leading to the promotion of VdMYB56 expression.Conclusively,the VdMYB56-VdMYB69 module is a positive regulator of anthocyanin biosynthesis in rabbiteye blueberry,which may provide new insights into high-anthocyanin breeding,particularly for the southern karstic regions.展开更多
Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations i...Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.展开更多
Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown ...Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.展开更多
Mounting evidence suggests that circadian rhythm disruption may be linked to the onset and progression of Alzheimer’s disease.However,whether this disruption occurs before the appearance of cognitive symptoms and whe...Mounting evidence suggests that circadian rhythm disruption may be linked to the onset and progression of Alzheimer’s disease.However,whether this disruption occurs before the appearance of cognitive symptoms and whether it drives disease development remain unclear.Understanding the temporal relationship between circadian rhythm dysregulation and early Alzheimer’s disease pathological changes may open up new avenues for disease prevention and intervention.To determine if circadian rhythm disruption precedes cognitive decline,we conducted high-resolution transcriptome analyses of the hippocampus in a 5-month-old mouse model of Alzheimer’s disease and age-matched wild-type control mice at multiple time points over a 24-hour period.While the mouse model of Alzheimer’s disease did not exhibit obvious cognitive symptoms at this stage,the expression of circadian-related genes in the hippocampus exhibited extensive abnormalities.In the control group,2109 genes exhibited rhythmic expression characteristics.In the mouse model of Alzheimer’s disease,a marked proportion of these genes lost their rhythmicity,some genes newly developed rhythmicity,and some maintained rhythmicity but with altered expression patterns.Genes related to neuronal function,including those involved in protein homeostasis regulation,neuroinflammation,and ion homeostasis,showed significant changes in circadian rhythm amplitude and phase,and some completely lost their rhythmicity.These findings point to the following critical early events in Alzheimer’s disease:hippocampal circadian gene disruption occurs before cognitive symptoms emerge,genes related to neuronal function are uniquely susceptible to this early dysregulation,and circadian dysfunction may even precede the pathological changes of Alzheimer’s disease and influence disease onset.This work advances Alzheimer’s disease research by clarifying that circadian disruption is an early pre-symptomatic event,reinforcing the potential of circadian rhythm regulation as a strategy for early intervention of Alzheimer’s disease,and identifying neuronal pathways that may serve as intervention targets.展开更多
As a common malignant tumor,the heterogeneity of colorectal cancer plays an important role in tumor progression and treatment response.In recent years,the rapid development of single-cell transcriptomics and spatial t...As a common malignant tumor,the heterogeneity of colorectal cancer plays an important role in tumor progression and treatment response.In recent years,the rapid development of single-cell transcriptomics and spatial transcriptomics technologies has provided new perspectives for resolving the heterogeneity of colorectal cancer.These techniques can reveal the complexity of cellular composition and their interactions in the tumor microenvironment,and thus facilitate a deeper understanding of tumor biology.However,in practical applications,researchers still face technical challenges such as data processing and result interpretation.The aim of this paper is to explore how to use artificial intelligence(AI)technology to enhance the research efficiency of single-cell and spatial transcriptomics,analyze the current research progress and its limitations,and explore how combining AI approaches can provide new ideas for decoding the heterogeneity of colorectal cancer,and ultimately provide theoretical basis and practical guidance for the clinical precision treatment.展开更多
Benzo[a]pyrene(B[a]P)is a carcinogenic environmental pollutant widely present in the environment and can enter the human body through the food chain.It is therefore essential to treat and remediate the B[a]P-contamina...Benzo[a]pyrene(B[a]P)is a carcinogenic environmental pollutant widely present in the environment and can enter the human body through the food chain.It is therefore essential to treat and remediate the B[a]P-contaminated environment.Microbial remediation of B[a]Pcontaminated environments is considered to be one of the most effective strategies,and the addition of biostimulants is a feasible method to further improve the effectiveness of microbial remediation.In this study,we used Bacillus subtilis MSC4 to screen for the stimulation of sodium gluconate,which promoted B[a]P degradation.Based on biochemical and transcriptomic analyses,Sodium gluconate was found to significantly increase the biomass of MSC4 and the expression of most genes involved in B[a]P degradation.Activities of central carbon metabolism,fatty acidβ-oxidation and oxidative phosphorylation were all promoted.The significant increase in acid-induced oxalate decarboxylase expression indicates a decrease in intracellular pH,which promoted the synthesis of acetoin and lactate.Genes involved in the nitrogen cycle,especially nitrification and denitrification,were significantly up-regulated,contributing to B[a]P degradation.Genes involved in the synthesis of enzyme cofactors,including thiamine,molybdenum cofactors,NAD and heme,were up-regulated,which contributes to increasing enzyme activity in metabolic pathways.Up-regulation of genes in flagella assembly,chemotaxis,and lipopeptide synthesis is beneficial for the dissolution and uptake of B[a]P.Genes related to the sugar transport system were upregulated,which facilitates the transport and absorption of monosaccharides and oligosaccharides by MSC4.This study provides a theoretical basis for the further application of sodium gluconate in the treatment of PAH-contaminated sites.展开更多
Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocyt...Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.展开更多
Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditio...Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise therapy.Methods:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker profiles.Data visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and astrocytes.Additionally,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular responses.Results:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius cells.YC showed a significant presence of Olfm3+ganglion neurons.ZEB1 gene knockout revealed changes in SMAD family gene expression,which regulate ferroptosis.Oxidative stress levels were also evaluated.Conclusion:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological research.Exercise may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.展开更多
文摘Rui Chena,b,Tangbing Cui a,b,∗a School of Biology and Biological Engineering,South China University of Technology,Guangzhou 510006,China b Guangdong Key Laboratory of Fermentation and Enzyme Engineering,South China University of Technology,Guangzhou 510006,China The authors regret that the published version of this article contained several errors and omissions,which are described and corrected below.1.Figs.3 and 4(figure order and legends).In the published article,Figs.3 and 4 were inadvertently published in reversed order.The figures should be swapped so that the figure content matches its caption.The correct figures and their legends are provided on the following page.2.Title correction.The compound name in the published title was incorrectly typeset as“benzo[a]pyrene”The correct spelling is“benzo[a]pyrene.”3.Text corrections in Section 2.4.Several typographical errors occurred in Section 2.4(“Up-regulation of acetoin,lactate,and kanosamine biosynthesis under sodium gluconate treatment”).
基金supported by the General Scientific Research Project of the Zhejiang Education Department,China(Grant No.Y202249221).
文摘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,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).
文摘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funded by the National Natural Science Foundation of China(32472401).
文摘As a specific spoilage organism of seafood under refrigerated temperature conditions,Shewanella spp.tend to form biofilms that exacerbate the occurrence of seafood spoilage.Biofilm-promoting factor A(BpfA)has been reported to promote the adhesion and biofilm formation of Shewanella spp.,but its role in adhesion and biofilm formation of S.putrefaciens under cold stress needs to be further investigated.To better comprehend the effect of BpfA on adhesion and biofilm formation of S.putrefaciens under cold stress(4℃),bacterial adhesion and biofilm phenotype of S.putrefaciens CN32 WT andΔbpfA at 4℃were analyzed and performed transcriptomics.The results showed that the deletion of bpfA had almost no effect on the growth of S.putrefaciens CN32 at 4℃,but weakened the unicellular adhesion capacity of S.putrefaciens CN32 and destabilized the stability of the multicellular adhesion layer.In addition,the biomass of the mature biofilm formed byΔbpfA was merely around 50%of that observed in the mature biofilm of S.putrefaciens CN32 WT,the average thickness and volume of the biofilm decreased by 18%and 27%,respectively,and the composition of the biofilm changed.Transcriptome analysis demonstrated that the deletion of bpfA led to differential expression of genes involved in metabolic pathways such as bacterial chemotaxis,two-component system,tyrosine metabolism,drug metabolism-other enzymes and biofilm formation-Vibrio cholerae,which in turn influenced bacterial adhesion and biofilm formation.Those results advance our acknowledgment of the character of BpfA on adhesion and biofilm formation of S.putrefaciens CN32,which contributes to understanding bacterial adhesion and the control of biofilm formation.
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).
文摘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 the National Key R&D Program of China,Nos.2021YFA1101703/2021YFA1101700(to YD).
文摘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.
基金National Natural Science Foundation of China,No.82471361(to MZ)the Natural Science Foundation for Excellent Young Scholars of Hunan Province,No.2021JJ20095(to MZ)+3 种基金the Key Research and Development Program of Hunan Province,No.2020SK2063(to MZ)the Research Project on Education and Teaching Innovation of Central South University,No.2021jy145(to MZ)the Natural Science Foundations of Hunan Province,No.2020JJ4134(to MZ)the Fundamental Research Funds for the Central Universities of Central South University,No.2023ZZTS0595(to YP).
文摘Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke.Here,we used a multi-omics approach combining single-cell and bulk transcriptomics.CellChat analysis revealed intercellular communication networks,while key genes were identified and predictive models built through Lasso regression.Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis.Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes.MicroRNA networks and transcription factors were investigated using mircode and RcisTarget.Experimental validation was performed using oxygen-glucose deprivation and transient middle cerebral artery occlusion models,focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function.We observed significantly elevated monocyte content in stroke brain tissue samples,and identified key monocyte genes associated with immune inflammation,chemokine signaling,and cell receptor function.A robust seven-gene predictive model for ischemic stroke was developed.CD274 strongly correlated with these seven genes,suggesting a potential immunomodulatory axis.In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes.In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen-glucose deprivation while reducing reactive oxygen species generation.In conclusion,this study maps post-stroke monocyte communication networks,identifies key signaling pathways,identifies regulatory mechanisms,and validates the functional importance of key genes,particularly abhydrolase domain-containing protein 2.These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.
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.
文摘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supported by National Natural Science Foundation of China grants(Nos.82173326 and 82473058)Key Research and Development Project of Sichuan Province(Nos.2024YFFK0374 and 2024YFFK0198)Interdisciplinary Innovation Project of West China College of Stomatology,Sichuan University(RD-03-202004).
文摘Microwave thermochemotherapy(MTC)has been applied to treat lip squamous cell carcinoma(LSCC),but a deeper understanding of its therapeutic mechanisms and molecular biology is needed.To address this,we used single-cell transcriptomics(scRNA-seq)and spatial transcriptomics(ST)to highlight the pivotal role of tumor-associated neutrophils(TANs)among tumor-infiltrating immune cells and their therapeutic response to MTC.MNDA+TANs with anti-tumor activity(N1-phenotype)are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion,and these TANs are characterized by enhanced cytotoxicity,ameliorated hypoxia,and upregulated IL1B,activating T&NK cells and fibroblasts via IL1B-IL1R.In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC,fibroblasts accumulated in the tumor front(TF)can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs(pro-tumor phenotype)via CXCL12-CXCR4,which results in the aggregation of N1-TANs and extracellular matrix(ECM)deposition.In addition,we construct an N1-TANs marker,MX2,which positively correlates with better prognosis in LSCC patients,and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin(H&E)-stained images so as to conveniently guide decision making in clinical practice.Collectively,our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
基金financially supported by the National Natural Science Foundation of China(32160578)Natural Science Foundation of Ningxia Hui Autonomous Region(2025AAC020032).
文摘Malolactic fermentation,started by lactic acid bacteria,plays a crucial role in the production of high-quality wines.As global warming increases the ethanol content in wines,the success of malolactic fermentation depends on selecting ethanol-tolerant strains,especially for wines from increasingly warm climates.Lentilactobacillus hilgardii Q19 was isolated and characterized as an indigenous malolactic bacterium with higher ethanol tolerance properties.In this study,it was indicated that ethanol stress had significant effects on ATPase activity,antioxidant system,and cell membrane of L.hilgardii Q19 by measuring the physiological indicators under stress which include H^(+)-ATPase,Na^(+)/K^(+)-ATPase,Ca^(2+)/Mg^(2+)-ATPase activity,glutathione content,superoxide dismutase(SOD)activity and intracellular reactive oxygen species(ROS)content.The main metabolic pathways involved in ethanol stress such as ATP-binding cassette(ABC)transporters,pentose phosphate pathway,phosphotransferase system,glutathione metabolic pathway and two-component systems were screened by transcriptome sequencing analysis.The functions of the pentose phosphate pathway,pyruvate metabolic pathway and glycerolipid metabolism under ethanol stress were verified by constructing the L.hilgardii Q19 ethanol stress related key genes gnt K,pyk,and glp K overexpression vectors.The above findings may contribute to our understanding of the metabolic pathways and regulatory mechanisms of L.hilgardii Q19 in response to ethanol stress.
基金financially supported by the Science and Technology Project of Nantong City(Grant No.JC2021097)the Key Project Fund for Clinical Medicine Special Program of Nantong University(Grant No.2024JZ043)Jiangsu Provincial Administration for Market Regulation Science and Technology Program Project(Grant No.KJ2026104).
文摘Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.
基金supported by Biological Breeding-Major Projects to Yun Ma(Grant No.2023ZD0404803)Key R&D Program of Ningxia Hui Autonomous Region to Lingkai Zhang(2023BBF01007)and(2023BCF01006)。
文摘Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dynamic transcription of bovine germ cell population.Results In this study,we used Stereo-seq to construct a spatial transcription map of bovine testicular tissue at two ages.Four germ cell groups and five somatic cell groups were determined,and functional enrichment characterized their different biological functions and the differences between calves and adult bulls.At the same time,we also defined the subpopulations of cells and marker genes,then,clarified the communications between germ cells.Conclusion Our study constructed a spatial transcription map of bovine testicular tissue for the first time,and systematically described the dynamic transcription changes during spermatogenesis.These data laid the foundation for the study of spermatogenesis in large mammals and elucidated the transcriptional dynamics underlying male germ cell development.
基金supported by grants from the Core Program grants of Guizhou Province,China(Grant No.QKHZDZXZ[2024]28)the Guizhou Provincial Science and Technology Projects of China(Grant No.YQK[2023]008)the Guizhou Provincial Scientific and Technological Program(Grant No.QKHFQ[2024]004-1).
文摘Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underlying the high anthocyanin accumulation during the fruit development and colouration of rabbiteye blueberry fruit,have not yet been fully clarified so far.The fruit anthocyanin content of rabbiteye blueberry in the karstic area of Guizhou Province,China,is much higher compared to that in other regions,and the fruit colour is highly affected by anthocyanin accumulation.Currently,the untargeted metabolomics and HPLC assays have been carried out using rabbiteye blueberry fruit at various stages,and it was investigated that cyanidin(Cy)and pelargonidin(Pg)reached their peaks at the red fruit(RF)stage,whereas delphinidin(Dp),petudinin(Pt),malvidin(Mv),and peonidin(Pn)got their ceilings at the mature fruit(MF)stage.Transcriptome and co-expression network analyses showed that 27 differentially expressed genes(DEGs)were associated with anthocyanin content,among which VdMYB56,belonging to the R2R3-MYB family,was markedly up-regulated during the development and colouration of fruit,and was significantly higher in the skin than in the pulp.Furthermore,VdMYB56-overexpressing tomato fruits demonstrated a substantial elevation in anthocyanin content on the 35th day after flowering(DAF).It was worth noting that VdMYB56 could directly bind to the promoter of Vd3GT to enhance its expression,thereby further strengthening the anthocyanin accumulation.Meantime,multiple assays verified that VdMYB69,an R2R3-MYB member,might interact with VdMYB56,leading to the promotion of VdMYB56 expression.Conclusively,the VdMYB56-VdMYB69 module is a positive regulator of anthocyanin biosynthesis in rabbiteye blueberry,which may provide new insights into high-anthocyanin breeding,particularly for the southern karstic regions.
基金supported by the National Natural Science Foundation of China(32270887,82272507,32200654,82430079,and 82472519)the National Key Research and Development Program of China(2022YFA1103202)+7 种基金the Chongqing High-End Medical Talents for Middle-aged and Young(YXGD202408)the Army Scientific and Technological Innovation Talents Prioritized Suppor t Program(2023-124)the Natural Science Foundation of Chongqing(CSTB2023NSCQ-ZDJO008)the Postdoctoral Innovative Talent Support Program(BX20220397)the Open Project of State Key Laboratory of TraumaBurns and Combined Injury(SFLKF202201)the Project for Enhancing Innovation of Army Medical University(2023XJS39)the Talent Innovation Training Program at the Army Medical Center(ZXZYTSYS09)。
文摘Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.
基金supported by the National Natural Science Foundation of China,Nos.82471123,82171053the Jilin Province Special Project for Talent in Medical and Health Sciences,No.2024WSXK-E01the Natural Science Foundation of Jilin Province,YDZJ202501ZYTS318(all to GL).
文摘Retinal ganglion cells,a crucial component of the central nervous system,are often affected by irreversible visual impairment due to various conditions,including trauma,tumors,ischemia,and glaucoma.Studies have shown that the optic nerve crush model and glaucoma model are commonly used to study retinal ganglion cell injury.While these models differ in their mechanisms,both ultimately result in retinal ganglion cell injury.With advancements in high-throughput technologies,techniques such as microarray analysis,RNA sequencing,and single-cell RNA sequencing have been widely applied to characterize the transcriptomic profiles of retinal ganglion cell injury,revealing underlying molecular mechanisms.This review focuses on optic nerve crush and glaucoma models,elucidating the mechanisms of optic nerve injury and neuron degeneration induced by glaucoma through single-cell transcriptomics,transcriptome analysis,and chip analysis.Research using the optic nerve crush model has shown that different retinal ganglion cell subtypes exhibit varying survival and regenerative capacities following injury.Single-cell RNA sequencing has identified multiple genes associated with retinal ganglion cell protection and regeneration,such as Gal,Ucn,and Anxa2.In glaucoma models,high-throughput sequencing has revealed transcriptomic changes in retinal ganglion cells under elevated intraocular pressure,identifying genes related to immune response,oxidative stress,and apoptosis.These genes are significantly upregulated early after optic nerve injury and may play key roles in neuroprotection and axon regeneration.Additionally,CRISPR-Cas9 screening and ATAC-seq analysis have identified key transcription factors that regulate retinal ganglion cell survival and axon regeneration,offering new potential targets for neurorepair strategies in glaucoma.In summary,single-cell transcriptomic technologies provide unprecedented insights into the molecular mechanisms underlying optic nerve injury,aiding in the identification of novel therapeutic targets.Future researchers should integrate advanced single-cell sequencing with multi-omics approaches to investigate cell-specific responses in retinal ganglion cell injury and regeneration.Furthermore,computational models and systems biology methods could help predict molecular pathways interactions,providing valuable guidance for clinical research on optic nerve regeneration and repair.
基金Shenzhen Science Technology and Innovation Commission,No.JCYJ20220531100811026Shenzhen Clinical Research Center for Trauma Treatment,No.LCYSSQ20220823091405012(both to YZ)Shenzhen Science and Technology Program,No.KQTD20240729102249044.
文摘Mounting evidence suggests that circadian rhythm disruption may be linked to the onset and progression of Alzheimer’s disease.However,whether this disruption occurs before the appearance of cognitive symptoms and whether it drives disease development remain unclear.Understanding the temporal relationship between circadian rhythm dysregulation and early Alzheimer’s disease pathological changes may open up new avenues for disease prevention and intervention.To determine if circadian rhythm disruption precedes cognitive decline,we conducted high-resolution transcriptome analyses of the hippocampus in a 5-month-old mouse model of Alzheimer’s disease and age-matched wild-type control mice at multiple time points over a 24-hour period.While the mouse model of Alzheimer’s disease did not exhibit obvious cognitive symptoms at this stage,the expression of circadian-related genes in the hippocampus exhibited extensive abnormalities.In the control group,2109 genes exhibited rhythmic expression characteristics.In the mouse model of Alzheimer’s disease,a marked proportion of these genes lost their rhythmicity,some genes newly developed rhythmicity,and some maintained rhythmicity but with altered expression patterns.Genes related to neuronal function,including those involved in protein homeostasis regulation,neuroinflammation,and ion homeostasis,showed significant changes in circadian rhythm amplitude and phase,and some completely lost their rhythmicity.These findings point to the following critical early events in Alzheimer’s disease:hippocampal circadian gene disruption occurs before cognitive symptoms emerge,genes related to neuronal function are uniquely susceptible to this early dysregulation,and circadian dysfunction may even precede the pathological changes of Alzheimer’s disease and influence disease onset.This work advances Alzheimer’s disease research by clarifying that circadian disruption is an early pre-symptomatic event,reinforcing the potential of circadian rhythm regulation as a strategy for early intervention of Alzheimer’s disease,and identifying neuronal pathways that may serve as intervention targets.
基金Supported by the Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Yantai Science and Technology Program,No.2024YD005,No.2024YD007 and No.2024YD010and Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06。
文摘As a common malignant tumor,the heterogeneity of colorectal cancer plays an important role in tumor progression and treatment response.In recent years,the rapid development of single-cell transcriptomics and spatial transcriptomics technologies has provided new perspectives for resolving the heterogeneity of colorectal cancer.These techniques can reveal the complexity of cellular composition and their interactions in the tumor microenvironment,and thus facilitate a deeper understanding of tumor biology.However,in practical applications,researchers still face technical challenges such as data processing and result interpretation.The aim of this paper is to explore how to use artificial intelligence(AI)technology to enhance the research efficiency of single-cell and spatial transcriptomics,analyze the current research progress and its limitations,and explore how combining AI approaches can provide new ideas for decoding the heterogeneity of colorectal cancer,and ultimately provide theoretical basis and practical guidance for the clinical precision treatment.
基金supported by the National Key R&D Program of China(No.2020YFC1808803).
文摘Benzo[a]pyrene(B[a]P)is a carcinogenic environmental pollutant widely present in the environment and can enter the human body through the food chain.It is therefore essential to treat and remediate the B[a]P-contaminated environment.Microbial remediation of B[a]Pcontaminated environments is considered to be one of the most effective strategies,and the addition of biostimulants is a feasible method to further improve the effectiveness of microbial remediation.In this study,we used Bacillus subtilis MSC4 to screen for the stimulation of sodium gluconate,which promoted B[a]P degradation.Based on biochemical and transcriptomic analyses,Sodium gluconate was found to significantly increase the biomass of MSC4 and the expression of most genes involved in B[a]P degradation.Activities of central carbon metabolism,fatty acidβ-oxidation and oxidative phosphorylation were all promoted.The significant increase in acid-induced oxalate decarboxylase expression indicates a decrease in intracellular pH,which promoted the synthesis of acetoin and lactate.Genes involved in the nitrogen cycle,especially nitrification and denitrification,were significantly up-regulated,contributing to B[a]P degradation.Genes involved in the synthesis of enzyme cofactors,including thiamine,molybdenum cofactors,NAD and heme,were up-regulated,which contributes to increasing enzyme activity in metabolic pathways.Up-regulation of genes in flagella assembly,chemotaxis,and lipopeptide synthesis is beneficial for the dissolution and uptake of B[a]P.Genes related to the sugar transport system were upregulated,which facilitates the transport and absorption of monosaccharides and oligosaccharides by MSC4.This study provides a theoretical basis for the further application of sodium gluconate in the treatment of PAH-contaminated sites.
基金supported by the National Natural Science Foundation of China,No.82301403(to DZ)。
文摘Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.
文摘Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise therapy.Methods:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker profiles.Data visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and astrocytes.Additionally,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular responses.Results:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius cells.YC showed a significant presence of Olfm3+ganglion neurons.ZEB1 gene knockout revealed changes in SMAD family gene expression,which regulate ferroptosis.Oxidative stress levels were also evaluated.Conclusion:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological research.Exercise may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.
