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
Anthocyanins are vital secondary metabolites contributing to fruit pigmentation and antioxidative properties.While light is a well-known regulator of anthocyanin biosynthesis,the molecular basis of light-independent a...Anthocyanins are vital secondary metabolites contributing to fruit pigmentation and antioxidative properties.While light is a well-known regulator of anthocyanin biosynthesis,the molecular basis of light-independent anthocyanin accumulation remains underexplored.In this study,integrated analysis of metabolome and transcriptome showed that the anthocyanin content in blueberry(Vaccinium corymbosum‘Bluetta’)fruit was slightly decreased by light-impermeable bagging treatment,while anthocyanin biosynthetic genes were transcriptionally inhibited to different levels,suggesting a slight influence of the bagging treatment on anthocyanin accumulation.Further observation showed that fruit bagging did not alter ethylene production but decreased ABA content.Noticeably,two VcMYBA/MYB1s were not transcriptionally altered by the light-impermeable bagging treatment.Consistently,histochemical GUS analysis and pharmacological manipulation suggested light-independent and ethylene-inducible expression of VcMYBA/MYB1.Moreover,WGCNA analysis revealed 3759 genes positively associated with MYBA/MYB1 such as ethylene-associated genes,etc.Additionally,VcbZIP55s and VcCOP1s were activated and inactivated by the bagging treatment,respectively.These findings provided a framework of light-independent anthocyanin biosynthesis in blueberry fruit.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
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
Atmospheric carbon dioxide(CO_(2))levels are escalating at an unprecedented rate,leading to the phenomenon of ocean acidification(OA).Parental exposure to acidification has the potential to enhance offspring resilienc...Atmospheric carbon dioxide(CO_(2))levels are escalating at an unprecedented rate,leading to the phenomenon of ocean acidification(OA).Parental exposure to acidification has the potential to enhance offspring resilience through cross-generation plasticity.In this study,we analyzed larval growth and transcriptomic profiles in the Pacific oyster,Crassostrea gigas,a species of significant ecological relevance,under both control and elevated CO_(2)conditions experienced by their parental generation.Our findings indicate that the oyster populations exposed to OA exhibited a higher incidence of abnormalities during the D-shaped larval stage,followed by accelerated growth at the eyed stage.Through a comparative transcriptomic investigation of eyed larvae(25 d after fertilization),we observed that parental exposure to OA substantially influenced the gene expression in the offspring.Genes associated with lipid catabolism and shell formation were notably upregulated in oysters with parental OA exposure,potentially playing a role in cross-generational conditioning and conferring resilience to OA stressors.These results underscore the profound impact of OA on oyster larval development via cross-generational mechanisms and shed light on the molecular underpinnings of cross-generation plasticity.展开更多
For red pear,the anthocyanin content is a crucial factor determining the fruit skin color,which affects consumer preferences.Low overnight temperatures promote anthocyanin accumulation,but the molecular mechanism resp...For red pear,the anthocyanin content is a crucial factor determining the fruit skin color,which affects consumer preferences.Low overnight temperatures promote anthocyanin accumulation,but the molecular mechanism responsible is unclear.In this study,‘Hongzaosu’pear(Pyrus pyrifolia×Pyrus communis)fruit were treated with a low nighttime temperature(LNT,16℃)or a warm nighttime temperature(WNT,26℃),with sampling conducted within two diurnal cycles.The results showed that LNT promoted anthocyanin accumulation in the fruit skin.The structural anthocyanin biosynthetic genes PpCHS,PpF3H,and PpUFGT exhibited a rhythmic increase in expression at night under LNT.To examine the underlying mechanism,RNA sequencing was conducted using pear calli exposed to LNT and WNT for different durations(24,48,72,or 96 h).Transcriptome analysis revealed 285 differentially expressed genes(DEGs)common to all pairwise comparisons of LNT-and WNT-treated calli of‘Clapp's Favorite’(P.communis)at the sampling time points.KEGG pathway and gene ontology enrichment analyses indicated that the common DEGs were enriched in secondary metabolic processes and phenylpropanoid metabolic processes,which are associated with anthocyanin biosynthesis.The transcription factor PpCDF5,which was responsive to LNT,was selected for further study.Dual-luciferase assays showed that PpCDF5 activated the transcription of anthocyanin biosynthetic genes PpMYB10,PpCHS,PpF3H,PpDFR,PpANS,and PpUFGT.The yeast one-hybrid and EMSA assays demonstrated that PpCDF5 directly binds to the PpF3H promoter,which contains an AAAG motif.Overexpression of PpCDF5 in pear calli and transient overexpression in pear fruit both increased anthocyanin accumulation.The results indicate that PpCDF5 is involved in LNT-induced anthocyanin biosynthesis in pear fruit and provide insights into the molecular regulation of commercial fruit coloration.展开更多
Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study ...Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study revealed that removing bags from‘Gengcunyangtao’red-fleshed peach fruits triggers the rapid and uniform accumulation of anthocyanins in the flesh,resulting in anthocyanin levels that exceed those in unbagged fruits.The exposure to light after bag removal triggered significant increases in anthocyanin levels within 24 h.This was accompanied by the rapid upregulation of light-responsive and flavonoid biosynthetic gene expression levels within 6 h.A metabolomic analysis indicated that anthocyanin precursors,especially p-coumaric acid,accumulated before bag removal,thereby increasing substrate availability for rapid anthocyanin synthesis.On the basis of a weighted gene co-expression network analysis,MYB transcription factors,anthocyanin transporters,glutathione S-transferase,and multidrug and toxic compound extrusion(MATE)were identified as key regulators that coordinate precursor storage along with light-induced transcriptional activation.Notably,PpMYB4 binds to the promoter of PpGSTF14 and activates its expression,thereby promoting anthocyanin accumulation.The study findings elucidated the temporal coordination of metabolic priming and light-responsive transcriptional regulation driving rapid anthocyanin biosynthesis,with possible implications for improving peach fruit flesh coloration.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
As its tuberous alkaloids induce valuable pharmacological effects,Pinellia ternata has considerable clinical value.However,its production currently fails to meet its demand.In vitro microtuber culture,combined with sa...As its tuberous alkaloids induce valuable pharmacological effects,Pinellia ternata has considerable clinical value.However,its production currently fails to meet its demand.In vitro microtuber culture,combined with salicylic acid(SA)elicitation,may provide an effective alternative to traditional field production.In this study,an in vitro P.ternata microtuber induction system was developed and used to evaluate SA-induced elicitation of alkaloid accumulation.The quality of in vitro microtubers was assessed by total alkaloid measurement,a cytotoxicity assay,and transcriptomic analysis.With or without SA treatment,P.ternata microtuber induction was achieved within 60 d using petiole-derived explants,with a microtuber proliferation rate of approximately 17 microtubers per explant.The total alkaloid content of in vitro microtubers elicited with 100μM SA was equivalent to that of field-grown tubers,while those not treated with SA contained lower alkaloid content.The cytotoxicity assay showed preliminary cytotoxic effects of SA-treated microtubers against the breast cancer cell line SUM159,comparable to field-grown tubers.Transcriptomic analysis revealed many differentially expressed genes(DEGs)in SA-treated in vitro microtubers.Six and twelve DEGs were annotated to the tropane,piperidine,and pyridine alkaloid pathway and the isoquinoline alkaloid pathway,respectively.RT-qPCR confirmed that the genes encoding spermidine synthase(c64642_g1),hyoscyamine(6S)-dioxygenase(c62620_g1),catechol oxidase(c61704_g3),monoamine oxidase(c65996_g3),and aspartate transaminase(c71069_g1)were significantly induced by SA.This study advances the production of P.ternata microtubers without field cultivation and provides considerable genetic information regarding SA-promoted alkaloid accumulation in P.ternata.展开更多
This study examined the potential response mechanisms of Ligilactobacillus salivarius AR612 to glucose stress through whole-genome and comparative transcriptome analysis.We obtained the basic genome information of L.s...This study examined the potential response mechanisms of Ligilactobacillus salivarius AR612 to glucose stress through whole-genome and comparative transcriptome analysis.We obtained the basic genome information of L.salivarius AR612.The full genome length of L.salivarius AR612 was 1970245 bp,with a GC content of 33.01%and 1894 coding genes.Moreover,we identified many genes associated with genetic adaptations to various stress factors,including temperature,p H,osmotic pressure,bile salts,and oxidative stress.Physiological analysis revealed that the growth and morphology of AR612 changed significantly under glucose stress,with a decrease in the maximum growth and irregular cell morphology.Furthermore,a comparison of transcriptome data indicated that glucose stress induced changes in the number of differential genes.Moreover,AR612 could respond to extracellular glucose stress by changing the expression of genes related to cell morphology,carbohydrate metabolism,amino acid metabolism,fatty acid synthesis,and nucleotide metabolism.This study provides valuable theoretical insights for future research on the adaptation of L.salivarius AR612 to nutritional stress and its application in industrial processes.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
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
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
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
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
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
[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treate...[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treated with quercetin.[Results]Statistical analysis showed that 1264 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 716 were significantly up-regulated and 548 were significantly down-regulated;191 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 129 were significantly up-regulated and 62 were significantly down-regulated.By comparing the expression differences of these mRNAs and miRNAs in different samples,six different expression patterns were clustered.The expression of the above miRNAs was verified by real-time quantitative PCR(qPCR),and the results were highly consistent with the transcriptome sequencing data.In addition,Gene Ontology annotation and functional enrichment analysis of miRNA target genes showed that CTGF,VHL and H19,which are related to the regulation of cell proliferation signal transduction,were predicted to be new targets of differential miRNAs such as miR494-3p and miR675-3p and may play an important regulatory role in the process of Quercetin inhibiting the proliferation of Sune-1 cells.[Conclusions]This study provides a basis for the rational use of anti-tumor functional components of traditional Chinese medicine,and also provides a theoretical basis for the targeted therapy of nasopharyngeal carcinoma.展开更多
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 National Key R&D Program of China(Grant No.2022YFD1600500)the National Natural Science Foundation of China(Grant No.32272680).
文摘Anthocyanins are vital secondary metabolites contributing to fruit pigmentation and antioxidative properties.While light is a well-known regulator of anthocyanin biosynthesis,the molecular basis of light-independent anthocyanin accumulation remains underexplored.In this study,integrated analysis of metabolome and transcriptome showed that the anthocyanin content in blueberry(Vaccinium corymbosum‘Bluetta’)fruit was slightly decreased by light-impermeable bagging treatment,while anthocyanin biosynthetic genes were transcriptionally inhibited to different levels,suggesting a slight influence of the bagging treatment on anthocyanin accumulation.Further observation showed that fruit bagging did not alter ethylene production but decreased ABA content.Noticeably,two VcMYBA/MYB1s were not transcriptionally altered by the light-impermeable bagging treatment.Consistently,histochemical GUS analysis and pharmacological manipulation suggested light-independent and ethylene-inducible expression of VcMYBA/MYB1.Moreover,WGCNA analysis revealed 3759 genes positively associated with MYBA/MYB1 such as ethylene-associated genes,etc.Additionally,VcbZIP55s and VcCOP1s were activated and inactivated by the bagging treatment,respectively.These findings provided a framework of light-independent anthocyanin biosynthesis in blueberry fruit.
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Supported by the Key Research and Development Program of Shandong(No.2022LZGC015)the National Key R&D Program of China(No.2022YFD2401400)+1 种基金the Taishan Scholars Program,the National Key R&D Program of China(No.2022YFD2400304)the Agricultural Seed Project of Shandong Key R&D Program(No.2024LZGCQY003)。
文摘Atmospheric carbon dioxide(CO_(2))levels are escalating at an unprecedented rate,leading to the phenomenon of ocean acidification(OA).Parental exposure to acidification has the potential to enhance offspring resilience through cross-generation plasticity.In this study,we analyzed larval growth and transcriptomic profiles in the Pacific oyster,Crassostrea gigas,a species of significant ecological relevance,under both control and elevated CO_(2)conditions experienced by their parental generation.Our findings indicate that the oyster populations exposed to OA exhibited a higher incidence of abnormalities during the D-shaped larval stage,followed by accelerated growth at the eyed stage.Through a comparative transcriptomic investigation of eyed larvae(25 d after fertilization),we observed that parental exposure to OA substantially influenced the gene expression in the offspring.Genes associated with lipid catabolism and shell formation were notably upregulated in oysters with parental OA exposure,potentially playing a role in cross-generational conditioning and conferring resilience to OA stressors.These results underscore the profound impact of OA on oyster larval development via cross-generational mechanisms and shed light on the molecular underpinnings of cross-generation plasticity.
基金supported by the National Natural Science Foundation of China(Grant Nos.32072545,32272639 and 32260745)Zhejiang Provincial Natural Science Foundation of China(Grant Nos.LTGN23C150009 and LY22C150003)Zhejiang University Experimental Technology Research Project(Grant No.SYBJS202217).
文摘For red pear,the anthocyanin content is a crucial factor determining the fruit skin color,which affects consumer preferences.Low overnight temperatures promote anthocyanin accumulation,but the molecular mechanism responsible is unclear.In this study,‘Hongzaosu’pear(Pyrus pyrifolia×Pyrus communis)fruit were treated with a low nighttime temperature(LNT,16℃)or a warm nighttime temperature(WNT,26℃),with sampling conducted within two diurnal cycles.The results showed that LNT promoted anthocyanin accumulation in the fruit skin.The structural anthocyanin biosynthetic genes PpCHS,PpF3H,and PpUFGT exhibited a rhythmic increase in expression at night under LNT.To examine the underlying mechanism,RNA sequencing was conducted using pear calli exposed to LNT and WNT for different durations(24,48,72,or 96 h).Transcriptome analysis revealed 285 differentially expressed genes(DEGs)common to all pairwise comparisons of LNT-and WNT-treated calli of‘Clapp's Favorite’(P.communis)at the sampling time points.KEGG pathway and gene ontology enrichment analyses indicated that the common DEGs were enriched in secondary metabolic processes and phenylpropanoid metabolic processes,which are associated with anthocyanin biosynthesis.The transcription factor PpCDF5,which was responsive to LNT,was selected for further study.Dual-luciferase assays showed that PpCDF5 activated the transcription of anthocyanin biosynthetic genes PpMYB10,PpCHS,PpF3H,PpDFR,PpANS,and PpUFGT.The yeast one-hybrid and EMSA assays demonstrated that PpCDF5 directly binds to the PpF3H promoter,which contains an AAAG motif.Overexpression of PpCDF5 in pear calli and transient overexpression in pear fruit both increased anthocyanin accumulation.The results indicate that PpCDF5 is involved in LNT-induced anthocyanin biosynthesis in pear fruit and provide insights into the molecular regulation of commercial fruit coloration.
基金supported by the Key Scientific and Technological Grant of Zhejiang for Breeding New Agricultural Varieties(Grant No.2021C12066-4)Huzhou Agricultural Science and Technology Innovation Team Project(Grant No.2022HN01).
文摘Red-fleshed fruits are valued for their vibrant color and high anthocyanin content.Pre-harvest fruit bagging enhances fruit peel pigmentation,but its effect on flesh coloration remains poorly characterized.This study revealed that removing bags from‘Gengcunyangtao’red-fleshed peach fruits triggers the rapid and uniform accumulation of anthocyanins in the flesh,resulting in anthocyanin levels that exceed those in unbagged fruits.The exposure to light after bag removal triggered significant increases in anthocyanin levels within 24 h.This was accompanied by the rapid upregulation of light-responsive and flavonoid biosynthetic gene expression levels within 6 h.A metabolomic analysis indicated that anthocyanin precursors,especially p-coumaric acid,accumulated before bag removal,thereby increasing substrate availability for rapid anthocyanin synthesis.On the basis of a weighted gene co-expression network analysis,MYB transcription factors,anthocyanin transporters,glutathione S-transferase,and multidrug and toxic compound extrusion(MATE)were identified as key regulators that coordinate precursor storage along with light-induced transcriptional activation.Notably,PpMYB4 binds to the promoter of PpGSTF14 and activates its expression,thereby promoting anthocyanin accumulation.The study findings elucidated the temporal coordination of metabolic priming and light-responsive transcriptional regulation driving rapid anthocyanin biosynthesis,with possible implications for improving peach fruit flesh coloration.
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 Key Project of Natural Science Research for Colleges and Universities in Anhui Province(2024AH051661,2023AH050345)Excellent Scientific Research and Innovation Team of University in Anhui Province(2022AH010029).
文摘As its tuberous alkaloids induce valuable pharmacological effects,Pinellia ternata has considerable clinical value.However,its production currently fails to meet its demand.In vitro microtuber culture,combined with salicylic acid(SA)elicitation,may provide an effective alternative to traditional field production.In this study,an in vitro P.ternata microtuber induction system was developed and used to evaluate SA-induced elicitation of alkaloid accumulation.The quality of in vitro microtubers was assessed by total alkaloid measurement,a cytotoxicity assay,and transcriptomic analysis.With or without SA treatment,P.ternata microtuber induction was achieved within 60 d using petiole-derived explants,with a microtuber proliferation rate of approximately 17 microtubers per explant.The total alkaloid content of in vitro microtubers elicited with 100μM SA was equivalent to that of field-grown tubers,while those not treated with SA contained lower alkaloid content.The cytotoxicity assay showed preliminary cytotoxic effects of SA-treated microtubers against the breast cancer cell line SUM159,comparable to field-grown tubers.Transcriptomic analysis revealed many differentially expressed genes(DEGs)in SA-treated in vitro microtubers.Six and twelve DEGs were annotated to the tropane,piperidine,and pyridine alkaloid pathway and the isoquinoline alkaloid pathway,respectively.RT-qPCR confirmed that the genes encoding spermidine synthase(c64642_g1),hyoscyamine(6S)-dioxygenase(c62620_g1),catechol oxidase(c61704_g3),monoamine oxidase(c65996_g3),and aspartate transaminase(c71069_g1)were significantly induced by SA.This study advances the production of P.ternata microtubers without field cultivation and provides considerable genetic information regarding SA-promoted alkaloid accumulation in P.ternata.
基金supported by the Natural Science Foundation of China(32272364)the Shanghai Education Committee Scientific Research Innovation Projects,China(2101070007800120)+2 种基金National Science Foundation for Distinguished Young Scholars(32025029)Shanghai Key Project in Synthetic Biology(23HC1400900)the Shanghai Engineering Research Center of 460 Food Microbiology Program(19DZ2281100).
文摘This study examined the potential response mechanisms of Ligilactobacillus salivarius AR612 to glucose stress through whole-genome and comparative transcriptome analysis.We obtained the basic genome information of L.salivarius AR612.The full genome length of L.salivarius AR612 was 1970245 bp,with a GC content of 33.01%and 1894 coding genes.Moreover,we identified many genes associated with genetic adaptations to various stress factors,including temperature,p H,osmotic pressure,bile salts,and oxidative stress.Physiological analysis revealed that the growth and morphology of AR612 changed significantly under glucose stress,with a decrease in the maximum growth and irregular cell morphology.Furthermore,a comparison of transcriptome data indicated that glucose stress induced changes in the number of differential genes.Moreover,AR612 could respond to extracellular glucose stress by changing the expression of genes related to cell morphology,carbohydrate metabolism,amino acid metabolism,fatty acid synthesis,and nucleotide metabolism.This study provides valuable theoretical insights for future research on the adaptation of L.salivarius AR612 to nutritional stress and its application in industrial processes.
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 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 Educational Research Project for Young and Middle-aged Teachers in Fujian Province(Science and Technology Category,JAT210477)。
文摘[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treated with quercetin.[Results]Statistical analysis showed that 1264 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 716 were significantly up-regulated and 548 were significantly down-regulated;191 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 129 were significantly up-regulated and 62 were significantly down-regulated.By comparing the expression differences of these mRNAs and miRNAs in different samples,six different expression patterns were clustered.The expression of the above miRNAs was verified by real-time quantitative PCR(qPCR),and the results were highly consistent with the transcriptome sequencing data.In addition,Gene Ontology annotation and functional enrichment analysis of miRNA target genes showed that CTGF,VHL and H19,which are related to the regulation of cell proliferation signal transduction,were predicted to be new targets of differential miRNAs such as miR494-3p and miR675-3p and may play an important regulatory role in the process of Quercetin inhibiting the proliferation of Sune-1 cells.[Conclusions]This study provides a basis for the rational use of anti-tumor functional components of traditional Chinese medicine,and also provides a theoretical basis for the targeted therapy of nasopharyngeal carcinoma.
