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
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
The WSC proteins produced by Penicillium expansum play a crucial role in causing blue mold on pears.To analyze the role of the WSC1 gene in the pathogenic process of this fungal pathogen,we conducted transcriptomic an...The WSC proteins produced by Penicillium expansum play a crucial role in causing blue mold on pears.To analyze the role of the WSC1 gene in the pathogenic process of this fungal pathogen,we conducted transcriptomic analysis of a WSC1 knockout(ΔWSC1)strain.The knockout of WSC1 significantly altered the gene expression profile in P.expansum,particularly for genes involved in cell wall integrity,signaling,stress response,and toxin production.The differential expression of these genes might make theΔWSC1 strain more vulnerable to environmental stress,while reducing the toxin production capacity,ultimately leading to a decrease in the pathogenicity.The transcriptomic analysis revealed that the expression of genes related to stress response signals,defense mechanisms and oxidative stress management changed when pear fruits were infected with theΔWSC1 strain.These changes may trigger a cascade of responses in pear fruits.In addition,compared with those infected with the wild-type strain,pear fruits infected with theΔWSC1 strain exhibited up-regulated expression of genes related to defense and oxidative stress.This study clarifies how the WSC1 gene influences P.expansum’s ability to infect pear fruits and how pear fruits respond to the infection.展开更多
Pear anthracnose,caused by Colletotrichum fructicola,is a devastating disease that seriously affects most pear varieties,compromising their yield and quality.However,effective control of this pathogen is lacking.Moreo...Pear anthracnose,caused by Colletotrichum fructicola,is a devastating disease that seriously affects most pear varieties,compromising their yield and quality.However,effective control of this pathogen is lacking.Moreover,the critical resistance responses to C.fructicola in pear are unknown.To investigate these resistance mechanisms of pear against C.fructicola,transcriptomic and metabolomic analyses were performed on the anthracnose-resistant variety‘Seli’and susceptible variety‘Cuiguan’after C.fructicola infection.Differentially expressed genes(DEGs)and differentially accumulated metabolites(DAMs)were mainly involved in metabolism and secondary metabolite synthetic pathways,includingα-linoleic acid metabolism,phenylalanine biosynthesis metabolism,unsaturated fatty acids biosynthesis,and biosynthesis of amino acids and their derivatives.In particular,the accumulation of unsaturated fatty acids(UFAs),amino acids,and their derivatives,such as linoleic acid and its derivatives,lauric acid,N-acetyl-L-glutamic acid,and L-proline,was significantly increased in‘Seli’after infection,while the amino acids of oxiglutatione and N-acetyl-L-glutamic acid,as well as the proanthocyanidins,were significantly decreased in‘Cuiguan’.These findings suggest that these metabolites may contribute to the differential anthracnose resistance between‘Seli’and‘Cuiguan’.Overall,our results provid new insights into the regulation of pear anthracnose resistance,which may assist in developing new control strategies and breeding anthracnose-resistant varieties.展开更多
Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An...Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.Results Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate(cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.Conclusions FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.展开更多
Salt stress is a critical factor affecting the growth and yield of rice.Egypt,the largest rice producer in North Africa and the Middle East,is facing contrasting challenges related to salinity in its agroecosystems.In...Salt stress is a critical factor affecting the growth and yield of rice.Egypt,the largest rice producer in North Africa and the Middle East,is facing contrasting challenges related to salinity in its agroecosystems.In this study,we compared the salt-induced responses among three rice varieties:Giza 176(Egyptian variety),Kaituodao(Chinese variety),and Pokkali(Sri Lanka variety,used as control)under normal and saline stress(100 mmol/L NaCl)conditions at two seedling stages through RNA-seq expression analysis.Giza 176 displayed a salt tolerance score of 7 on the SES(Standard Evaluation Score).Its transcriptome showed dynamic changes,with the number of upregulated genes increasing from 180 to 735,and downregulated genes increasing from 918 to 2930 from the one-week to two-week stress stages,with activated pathways in ion transport,reactive oxygen species(ROS)scavenging,and protein biosynthesis.展开更多
Although coagulase-negative Staphylococcus(CNS),along with technological activities,plays a key role in fermented sausage flavour and nutrient production,the molecular mechanism of these activities remains elusive.In ...Although coagulase-negative Staphylococcus(CNS),along with technological activities,plays a key role in fermented sausage flavour and nutrient production,the molecular mechanism of these activities remains elusive.In this study,18 CNS strains with high proteolytic activity were isolated from Chinese Dong fermented pork(Nanx Wudl),and their technological and transcriptomic properties were investigated.After biochemical identification and genetic analysis,their technological properties,including nitrate reductase,catalase,antioxidant,and lipolytic activities and their growth under varying temperatures,salt concentrations,and p H levels were evaluated.Their aroma-producing potential was also determined in a model medium resembling fermented sausages.Transcriptomic analysis was performed using the most promising isolates.Biochemical identification and 16S rDNA sequencing revealed that the 18 Staphylococcus strains belonged to Staphylococcus xylosus,Staphylococcus saprophyticus,Staphylococcus carnosus,Staphylococcus sciuri,and Staphylococcus equorum.In terms of technological properties,16 strains showed a nitrate-reducing ability,while 11 strains had a lipolytic activity.All strains exhibited superoxide dismutase(SOD)and catalase activities;four strains displayed an SOD activity of>50%.They also tolerated 10%NaCl and 150 mg/kg of nitrite.They showed significant differences in ketone and acid production.The transcriptomic analysis of S.xylosus strains Sx3 and Sx6,which were selected because of their excellent enzymatic activities and aroma-producing ability,revealed the remarkable effect of genes related to pyruvate catabolism and amino acid metabolism on aroma generation.Therefore,this study provided valuable insights into the metabolic mechanisms underlying the technological properties of CNS and identified promising candidates as starter cultures in fermented sausage manufacturing.展开更多
[Objectives]To study the effect of carcinoma cell line(HepG2)and mechanism of anti-tumor activity of cucurbitacin B(CuB)and cucurbitacin E(CuE)on HepG2 cells.[Methods]HepG2 cells were treated with various concentratio...[Objectives]To study the effect of carcinoma cell line(HepG2)and mechanism of anti-tumor activity of cucurbitacin B(CuB)and cucurbitacin E(CuE)on HepG2 cells.[Methods]HepG2 cells were treated with various concentrations of CuB and CuE,and the proliferation,cell cycle distribution,apoptosis,and performed RNA-seqtranscriptomics of these cells were evaluated after treatment.[Results]The results demonstrated that,in comparison to the control group,HepG2 cells treated with CuB and CuE displayed a synergistic effect on growth inhibition,cell cycle arrest at the G 2/M phase,and apoptosis induction in a concentration-and time-dependent manner.Western blotting analysis using protein extracts derived from HepG2 cells showed that CuB and CuE induced apoptosis by increasing the expression of endogenous levels of full-length caspase-3(35 kDa)and the large fragment of cleaved caspase-3(17 kDa).Moreover,transcriptomic results demonstrated that after treatment,the differentially expressed genes associated with pathways such as"cell cycle","spliceosome","metabolic pathways",and"carbon metabolism"were significantly up-/down-regulated.[Conclusions]These results demonstrate that the anti-tumor mechanisms of CuB and CuE are attributed to their interference in cell cycle and metabolism processes.Collectively,the treatment with CuB and CuE may serve as a promising therapeutic option for hepatocellular carcinoma.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 Endometriosis is a clinical condition characterized by the presence of endometrial glands outside the uterine cavity.While its incidence remains mostly uncertain,endometriosis impacts around 180 million wom...BACKGROUND Endometriosis is a clinical condition characterized by the presence of endometrial glands outside the uterine cavity.While its incidence remains mostly uncertain,endometriosis impacts around 180 million women worldwide.Despite the presentation of several epidemiological and clinical explanations,the precise mechanism underlying the disease remains ambiguous.In recent years,researchers have examined the hereditary dimension of the disease.Genetic research has aimed to discover the gene or genes responsible for the disease through association or linkage studies involving candidate genes or DNA mapping techniques.AIM To identify genetic biomarkers linked to endometriosis by the application of machine learning(ML)approaches.METHODS This case-control study accounted for the open-access transcriptomic data set of endometriosis and the control group.We included data from 22 controls and 16 endometriosis patients for this purpose.We used AdaBoost,XGBoost,Stochasting Gradient Boosting,Bagged Classification and Regression Trees(CART)for classification using five-fold cross validation.We evaluated the performance of the models using the performance measures of accuracy,balanced accuracy,sensitivity,specificity,positive predictive value,negative predictive value and F1 score.RESULTS Bagged CART gave the best classification metrics.The metrics obtained from this model are 85.7%,85.7%,100%,75%,75%,100%and 85.7%for accuracy,balanced accuracy,sensitivity,specificity,positive predictive value,negative predictive value and F1 score,respectively.Based on the variable importance of modeling,we can use the genes CUX2,CLMP,CEP131,EHD4,CDH24,ILRUN,LINC01709,HOTAIR,SLC30A2 and NKG7 and other transcripts with inaccessible gene names as potential biomarkers for endometriosis.CONCLUSION This study determined possible genomic biomarkers for endometriosis using transcriptomic data from patients with/without endometriosis.The applied ML model successfully classified endometriosis and created a highly accurate diagnostic prediction model.Future genomic studies could explain the underlying pathology of endometriosis,and a non-invasive diagnostic method could replace the invasive ones.展开更多
BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,pe...BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,peripheral blood mononuclear cells(PBMCs)serve as a robust model for investigating intracellular alterations linked to SZ.AIM To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ.METHODS PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes(DEGs)and differentially expressed proteins while mapping putative disease-associated signaling pathways.Key findings were validated using western blot(WB)and real-time fluorescence quantitative PCR(RT-qPCR).RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro,with subsequent verification of target gene expression via RT-qPCR.The levels of neuronal conduction proteins,including calmodulin-dependent protein kinase II(caMKII),CREB,and BDNF,were assessed through WB.Apoptosis was quantified by flow cytometry,while cell proliferation and viability were evaluated using the Cell Counting Kit-8 assay.RESULTS The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes,among which 25 DEGs were significantly altered between the SZ group and healthy controls.Notably,haptoglobin(HP),lactotransferrin(LTF),and SERPING1 exhibited marked upregulation.KEGG pathway enrichment analysis implicated neuroactive ligand-receptor interaction pathways in disease pathogenesis.Clinical sample validation demonstrated elevated protein and mRNA levels of HP,LTF,and SERPING1 in the SZ group compared to controls.WB analysis of all clinical samples further corroborated the significant upregulation of SERPING1.In hippocampal CA1 neurons transfected with lentivirus,reduced SERPING1 expression was accompanied by increased levels of CaMKII,CREB,and BDNF,enhanced cell viability,and reduced apoptosis.CONCLUSION SERPING1 may suppress neural cell proliferation in SZ patients via modulation of the CaMKII-CREB-BDNF signaling pathway.展开更多
Taxus cuspidata,a rare species of the Taxus genus,and its wild resources are under severe threat.The development of cultivated species has become an important strategy to replace wild species.The objective of this wor...Taxus cuspidata,a rare species of the Taxus genus,and its wild resources are under severe threat.The development of cultivated species has become an important strategy to replace wild species.The objective of this work was to elucidate the differences in secondary metabolite accumulation,particularly in the paclitaxel biosynthesis pathway,between wild and cultivated species.This study employed liquid chromatography-tandem mass spectrometry(LC-MS/MS)and RNA sequencing(RNA-Seq)technologies to conduct integrated metabolomic and transcriptomic analyses of wild and cultivated species of T.cuspidata.The results showed that the content of paclitaxel in cultivated species was significantly higher than in wild species,reaching 1.67 times that of the latter(p 0.01).Additionally,the<content of key paclitaxel precursors,GGPP and 10-deacetylbaccatin III,in cultivated species was 1.94 times(p 0.05)<and 1.71 times(p 0.01)higher than in wild species,respectively.Transcriptomic analysis identified 2606 differentially<expressed genes(DEGs),among which key enzyme genes related to paclitaxel biosynthesis(such as DXS,DXR,GGPS,etc.)were generally upregulated in cultivated species.Multiple key enzyme genes in both the 2-C-methyl-D-erythritol 4-phosphate pathway(MEP)and paclitaxel biosynthesis pathways were significantly upregulated in cultivated species.Conversely,genes and metabolites related to sugar metabolism were found to be higher in content in wild species.These findings reveal the significant advantage of cultivated species in paclitaxel production capacity,providing new insights into the metabolic regulation mechanisms during yew domestication.This has important implications for optimizing paclitaxel biosynthesis and guiding future improvements in T.cuspidata cultivars.展开更多
Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat ...Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat model of acute pneumonia was developed by treating rats with lipopolysaccharide(LPS)through a non-exposed tracheal drip.The pharmacological effects of HQSGD were evaluated via histopathological analysis of rat lung tissues,histological scoring of lung injury,assessment of lung index,serum inflammatory factors,oxidative stress levels,western blotting,and qRT-PCR.The active compounds of HQSGD were detected utilizing ultra-performance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS).NP and transcriptomic analysis were integrated to determine signaling pathways implicated in the pharmacological activity of HQSGD.The expression levels of mRNA and protein for factors implicated in these pathways were evaluated in rat lung tissues via qRT-PCR and western blotting,respectively.Results:HQSGD alleviated acute pneumonia in rats by reducing the lung index and the levels of TNF-α,IL-1β,CRP,and MDA while increasing the levels of SOD.The UPLC-MS/MS and NP techniques facilitated the identification of 28 bioactive constituents present in HQSGD.The principal 20 KEGG pathways were identified by intersecting the targets of HQSGD with pneumonia-related targets.These pathways were screened by comparing the transcriptomic data of the blank and model cohorts and those of the model and drug administration cohorts.GO and KEGG analyses indicated that the PI3K/AKT/NF-κB pathway was a potentially effective target of HQSGD.Conclusion:This investigation revealed the overall multi-component,multi-target,and multi-pathway interactions of HQSGD in the treatment of acute pneumonia.展开更多
The amniote pallium,a vital component of the forebrain,exhibits considerable evolutionary divergence across species and mediates diverse functions,including sensory processing,memory formation,and learning.However,the...The amniote pallium,a vital component of the forebrain,exhibits considerable evolutionary divergence across species and mediates diverse functions,including sensory processing,memory formation,and learning.However,the relationships among pallial subregions in different species remain poorly characterized,particularly regarding the identification of homologous neurons and their transcriptional signatures.In this study,we utilized singlenucleus RNA sequencing to examine over 130?000 nuclei from the macaque(Macaca fascicularis)neocortex,complemented by datasets from humans(Homo sapiens),mice(Mus musculus),zebra finches(Taeniopygia guttata),turtles(Chrysemys picta bellii),and lizards(Pogona vitticeps),enablingcomprehensivecross-species comparison.Results revealed transcriptomic conservation and species-specific distinctions within the amniote pallium.Notable similarities were observed among cell subtypes,particularly within PVALB+inhibitory neurons,which exhibited species-preferred subtypes.Furthermore,correlations between pallial subregions and several transcription factor candidates were identified,including RARB,DLX2,STAT6,NR3C1,and THRB,with potential regulatory roles in gene expression in mammalian pallial neurons compared to their avian and reptilian counterparts.These results highlight the conserved nature of inhibitory neurons,remarkable regional divergence of excitatory neurons,and species-specific gene expression and regulation in amniote pallial neurons.Collectively,these findings provide valuable insights into the evolutionary dynamics of the amniote pallium.展开更多
A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing po...A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing potential therapeutic targets.Here,we present an analytical strategy for the deep discovery of heterogeneous metabolism and drug response in the heart tissue of rats with HF using airflow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)coupled with bulk RNAsequencing.Spatial metabolomics illustrated pronounced metabolic heterogeneity between the infarct(I),infarct margin(IM),and non-infarct(NI)areas of heart tissue in HF.Integrated transcriptomics showed that increased mRNA expression of ATP citrate lyase disrupted the tricarboxylic acid(TCA)cycle in the NI area.Impairment of the carnitine shuttle system led to a significant accumulation of carnitines,suggesting potential abnormalities in fatty acid(FA)oxidation.Coupling on-tissue chemical derivatization with AFADESI-MSI enabled us to confirm the occurrence of incomplete oxidation of FAs in the NI area.Additionally,we observed a heterogeneous drug response between the anti-HF medications valsartan and Qishen Yiqi Dripping Pills(QDP).Valsartan exhibited a more pronounced effect on metabolic regulation in the I area,whereas QDP exerted stronger regulatory effects on metabolism in the NI area.Utilizing this method,four potential therapeutic targets were identified in HF:CPT1A,PDHB,ACLY,and BCAT2,which were preliminarily validated by western blotting.Overall,integrating spatial metabolomics with transcriptomics facilitates comprehensive analyses that link differential metabolites and genes,enabling a more precise characterization of metabolic changes in heart injury microareas and providing effective methods for elucidating molecular mechanisms and identifying potential therapeutic targets for HF.展开更多
Pigs have emerged as valuable large-animal models for cardiac xenotransplantation;however,the temporal dynamics of myocardial development in this species remains insufficiently defined.This study analyzed gene express...Pigs have emerged as valuable large-animal models for cardiac xenotransplantation;however,the temporal dynamics of myocardial development in this species remains insufficiently defined.This study analyzed gene expression patterns across four key developmental stages(neonatal,juvenile,sexual maturity,and adulthood)to delineate the molecular mechanisms driving porcine myocardial development.Increases in heart weight were accompanied by proportional expansion of myocardial fiber area and chamber size,reflecting coordinated structural development.Transcriptomic profiling of myocardial tissue by RNA sequencing(RNA-seq)identified 2189 differentially expressed genes(DEGs)across stage comparisons.Short time-series expression miner(STEM)analysis classified these DEGs into four major expression clusters enriched in pathways associated with myocardial development,immune responses,cell proliferation,and metabolic processes.Among 359 DEGs conserved across all developmental stages,six candidate genes were strongly associated with myocardial development.Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)confirmed a significant correlation between the expression of these candidate genes and myocardial development in porcine tissue.These findings establish a transcriptomic framework for porcine myocardial maturation and provide a molecular basis for advancing cardiac xenotransplantation.展开更多
The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of...The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of A. alternata under fludioxonil fungicide stress, the fungus was cultured at the half-maximal effective concentration (EC₅₀) of fludioxonil. Transcriptomic and metabolomic profiles were analyzed using mycelia harvested under these conditions. Comparative analysis revealed 1,001 differentially expressed genes (DEGs) in the resistant strain (RS) relative to the wild-type strain (WT), comprising 628 upregulated and 373 downregulated genes. Concurrently, 524 differentially accumulated metabolites (DAMs) were identified, with 336 upregulated and 188 downregulated metabolites. KEGG pathway enrichment demonstrated pronounced upregulation in glycerophospholipid metabolism, α-linolenic acid metabolism, nucleic acid biosynthesis, and glycosylation processes. Conversely, arachidonic acid and galactose metabolism pathways were suppressed. Significant downregulation was observed in phosphatidylinositol signaling, aflatoxin biosynthesis, and cutin/suberin/wax biosynthesis pathways. Transcriptomic profiling further indicated that upregulated DEGs were predominantly associated with amino sugar/nucleotide sugar metabolism, ABC transporters, aflatoxin biosynthesis, and purine metabolism, while downregulated DEGs were enriched in N-glycan biosynthesis, endoplasmic reticulum protein processing, steroid biosynthesis, and riboflavin metabolism. Fludioxonil exerted substantial inhibitory effects on fungal growth, pathogenicity, and metabolic activity. Mechanistically, A. alternata counteracted fungicide-induced stress through modulation of its antioxidant defense system. This integrative multi-omics study delineates the dynamic gene expression and metabolic reprogramming in A. alternata under fludioxonil exposure, providing novel insights into potential molecular targets and informing the development of next-generation fungicidal strategies for phytopathogen control.展开更多
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 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.
文摘The WSC proteins produced by Penicillium expansum play a crucial role in causing blue mold on pears.To analyze the role of the WSC1 gene in the pathogenic process of this fungal pathogen,we conducted transcriptomic analysis of a WSC1 knockout(ΔWSC1)strain.The knockout of WSC1 significantly altered the gene expression profile in P.expansum,particularly for genes involved in cell wall integrity,signaling,stress response,and toxin production.The differential expression of these genes might make theΔWSC1 strain more vulnerable to environmental stress,while reducing the toxin production capacity,ultimately leading to a decrease in the pathogenicity.The transcriptomic analysis revealed that the expression of genes related to stress response signals,defense mechanisms and oxidative stress management changed when pear fruits were infected with theΔWSC1 strain.These changes may trigger a cascade of responses in pear fruits.In addition,compared with those infected with the wild-type strain,pear fruits infected with theΔWSC1 strain exhibited up-regulated expression of genes related to defense and oxidative stress.This study clarifies how the WSC1 gene influences P.expansum’s ability to infect pear fruits and how pear fruits respond to the infection.
基金supported by the China Agriculture Research System(CARS-28-14)the National Natural Science Foundation of China(32302484)the University Natural Science Research Project of Anhui Province,China(2022AHO50926 and 2022AH040129).
文摘Pear anthracnose,caused by Colletotrichum fructicola,is a devastating disease that seriously affects most pear varieties,compromising their yield and quality.However,effective control of this pathogen is lacking.Moreover,the critical resistance responses to C.fructicola in pear are unknown.To investigate these resistance mechanisms of pear against C.fructicola,transcriptomic and metabolomic analyses were performed on the anthracnose-resistant variety‘Seli’and susceptible variety‘Cuiguan’after C.fructicola infection.Differentially expressed genes(DEGs)and differentially accumulated metabolites(DAMs)were mainly involved in metabolism and secondary metabolite synthetic pathways,includingα-linoleic acid metabolism,phenylalanine biosynthesis metabolism,unsaturated fatty acids biosynthesis,and biosynthesis of amino acids and their derivatives.In particular,the accumulation of unsaturated fatty acids(UFAs),amino acids,and their derivatives,such as linoleic acid and its derivatives,lauric acid,N-acetyl-L-glutamic acid,and L-proline,was significantly increased in‘Seli’after infection,while the amino acids of oxiglutatione and N-acetyl-L-glutamic acid,as well as the proanthocyanidins,were significantly decreased in‘Cuiguan’.These findings suggest that these metabolites may contribute to the differential anthracnose resistance between‘Seli’and‘Cuiguan’.Overall,our results provid new insights into the regulation of pear anthracnose resistance,which may assist in developing new control strategies and breeding anthracnose-resistant varieties.
基金supported by the Beijing Natural Science Foundation (grant number: 7232060)National Key Research and Development Program of China (grant number: 2023YFC2307301)Top Level Public Health Technical Personnel Training Plan (grant number: LJRC-03-09)。
文摘Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.Results Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate(cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.Conclusions FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
基金funded by the National Key R&D Program of China(Grant No.2022YFE0139400)the Egyptian-Chinese Research Fund,and Science,Technology&Innovation Funding Authority Egypt(Grant No.46512)the National Natural Science Foundation of China(Grant No.261143470).
文摘Salt stress is a critical factor affecting the growth and yield of rice.Egypt,the largest rice producer in North Africa and the Middle East,is facing contrasting challenges related to salinity in its agroecosystems.In this study,we compared the salt-induced responses among three rice varieties:Giza 176(Egyptian variety),Kaituodao(Chinese variety),and Pokkali(Sri Lanka variety,used as control)under normal and saline stress(100 mmol/L NaCl)conditions at two seedling stages through RNA-seq expression analysis.Giza 176 displayed a salt tolerance score of 7 on the SES(Standard Evaluation Score).Its transcriptome showed dynamic changes,with the number of upregulated genes increasing from 180 to 735,and downregulated genes increasing from 918 to 2930 from the one-week to two-week stress stages,with activated pathways in ion transport,reactive oxygen species(ROS)scavenging,and protein biosynthesis.
基金the financial support of the National Natural Science Foundation of China(32102016)the Taishan Industrial Experts Program。
文摘Although coagulase-negative Staphylococcus(CNS),along with technological activities,plays a key role in fermented sausage flavour and nutrient production,the molecular mechanism of these activities remains elusive.In this study,18 CNS strains with high proteolytic activity were isolated from Chinese Dong fermented pork(Nanx Wudl),and their technological and transcriptomic properties were investigated.After biochemical identification and genetic analysis,their technological properties,including nitrate reductase,catalase,antioxidant,and lipolytic activities and their growth under varying temperatures,salt concentrations,and p H levels were evaluated.Their aroma-producing potential was also determined in a model medium resembling fermented sausages.Transcriptomic analysis was performed using the most promising isolates.Biochemical identification and 16S rDNA sequencing revealed that the 18 Staphylococcus strains belonged to Staphylococcus xylosus,Staphylococcus saprophyticus,Staphylococcus carnosus,Staphylococcus sciuri,and Staphylococcus equorum.In terms of technological properties,16 strains showed a nitrate-reducing ability,while 11 strains had a lipolytic activity.All strains exhibited superoxide dismutase(SOD)and catalase activities;four strains displayed an SOD activity of>50%.They also tolerated 10%NaCl and 150 mg/kg of nitrite.They showed significant differences in ketone and acid production.The transcriptomic analysis of S.xylosus strains Sx3 and Sx6,which were selected because of their excellent enzymatic activities and aroma-producing ability,revealed the remarkable effect of genes related to pyruvate catabolism and amino acid metabolism on aroma generation.Therefore,this study provided valuable insights into the metabolic mechanisms underlying the technological properties of CNS and identified promising candidates as starter cultures in fermented sausage manufacturing.
文摘[Objectives]To study the effect of carcinoma cell line(HepG2)and mechanism of anti-tumor activity of cucurbitacin B(CuB)and cucurbitacin E(CuE)on HepG2 cells.[Methods]HepG2 cells were treated with various concentrations of CuB and CuE,and the proliferation,cell cycle distribution,apoptosis,and performed RNA-seqtranscriptomics of these cells were evaluated after treatment.[Results]The results demonstrated that,in comparison to the control group,HepG2 cells treated with CuB and CuE displayed a synergistic effect on growth inhibition,cell cycle arrest at the G 2/M phase,and apoptosis induction in a concentration-and time-dependent manner.Western blotting analysis using protein extracts derived from HepG2 cells showed that CuB and CuE induced apoptosis by increasing the expression of endogenous levels of full-length caspase-3(35 kDa)and the large fragment of cleaved caspase-3(17 kDa).Moreover,transcriptomic results demonstrated that after treatment,the differentially expressed genes associated with pathways such as"cell cycle","spliceosome","metabolic pathways",and"carbon metabolism"were significantly up-/down-regulated.[Conclusions]These results demonstrate that the anti-tumor mechanisms of CuB and CuE are attributed to their interference in cell cycle and metabolism processes.Collectively,the treatment with CuB and CuE may serve as a promising therapeutic option for hepatocellular carcinoma.
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approved by the Inonu University institutional review board for noninterventional studies(Approval No:2022/3842).
文摘BACKGROUND Endometriosis is a clinical condition characterized by the presence of endometrial glands outside the uterine cavity.While its incidence remains mostly uncertain,endometriosis impacts around 180 million women worldwide.Despite the presentation of several epidemiological and clinical explanations,the precise mechanism underlying the disease remains ambiguous.In recent years,researchers have examined the hereditary dimension of the disease.Genetic research has aimed to discover the gene or genes responsible for the disease through association or linkage studies involving candidate genes or DNA mapping techniques.AIM To identify genetic biomarkers linked to endometriosis by the application of machine learning(ML)approaches.METHODS This case-control study accounted for the open-access transcriptomic data set of endometriosis and the control group.We included data from 22 controls and 16 endometriosis patients for this purpose.We used AdaBoost,XGBoost,Stochasting Gradient Boosting,Bagged Classification and Regression Trees(CART)for classification using five-fold cross validation.We evaluated the performance of the models using the performance measures of accuracy,balanced accuracy,sensitivity,specificity,positive predictive value,negative predictive value and F1 score.RESULTS Bagged CART gave the best classification metrics.The metrics obtained from this model are 85.7%,85.7%,100%,75%,75%,100%and 85.7%for accuracy,balanced accuracy,sensitivity,specificity,positive predictive value,negative predictive value and F1 score,respectively.Based on the variable importance of modeling,we can use the genes CUX2,CLMP,CEP131,EHD4,CDH24,ILRUN,LINC01709,HOTAIR,SLC30A2 and NKG7 and other transcripts with inaccessible gene names as potential biomarkers for endometriosis.CONCLUSION This study determined possible genomic biomarkers for endometriosis using transcriptomic data from patients with/without endometriosis.The applied ML model successfully classified endometriosis and created a highly accurate diagnostic prediction model.Future genomic studies could explain the underlying pathology of endometriosis,and a non-invasive diagnostic method could replace the invasive ones.
基金Supported by the Key R&D Projects of Hainan Province,No.ZDYF2022SHFZ295.
文摘BACKGROUND Schizophrenia(SZ),a chronic and widespread brain disorder,presents with complex etiology and pathogenesis that remain inadequately understood.Despite the absence of a universally recognized endophenotype,peripheral blood mononuclear cells(PBMCs)serve as a robust model for investigating intracellular alterations linked to SZ.AIM To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ.METHODS PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes(DEGs)and differentially expressed proteins while mapping putative disease-associated signaling pathways.Key findings were validated using western blot(WB)and real-time fluorescence quantitative PCR(RT-qPCR).RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro,with subsequent verification of target gene expression via RT-qPCR.The levels of neuronal conduction proteins,including calmodulin-dependent protein kinase II(caMKII),CREB,and BDNF,were assessed through WB.Apoptosis was quantified by flow cytometry,while cell proliferation and viability were evaluated using the Cell Counting Kit-8 assay.RESULTS The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes,among which 25 DEGs were significantly altered between the SZ group and healthy controls.Notably,haptoglobin(HP),lactotransferrin(LTF),and SERPING1 exhibited marked upregulation.KEGG pathway enrichment analysis implicated neuroactive ligand-receptor interaction pathways in disease pathogenesis.Clinical sample validation demonstrated elevated protein and mRNA levels of HP,LTF,and SERPING1 in the SZ group compared to controls.WB analysis of all clinical samples further corroborated the significant upregulation of SERPING1.In hippocampal CA1 neurons transfected with lentivirus,reduced SERPING1 expression was accompanied by increased levels of CaMKII,CREB,and BDNF,enhanced cell viability,and reduced apoptosis.CONCLUSION SERPING1 may suppress neural cell proliferation in SZ patients via modulation of the CaMKII-CREB-BDNF signaling pathway.
基金supported by grants from the National Science Foundation of China to Yanwen Zhang(32272757,31972363)grants from Liaoning Provincial Department of Education Project to Dandan Wang(JYTMS20230698)grants from the Liaoning Provincial Science and Technology.Fund Project to Dandan Wang(2023JH2/101700200).
文摘Taxus cuspidata,a rare species of the Taxus genus,and its wild resources are under severe threat.The development of cultivated species has become an important strategy to replace wild species.The objective of this work was to elucidate the differences in secondary metabolite accumulation,particularly in the paclitaxel biosynthesis pathway,between wild and cultivated species.This study employed liquid chromatography-tandem mass spectrometry(LC-MS/MS)and RNA sequencing(RNA-Seq)technologies to conduct integrated metabolomic and transcriptomic analyses of wild and cultivated species of T.cuspidata.The results showed that the content of paclitaxel in cultivated species was significantly higher than in wild species,reaching 1.67 times that of the latter(p 0.01).Additionally,the<content of key paclitaxel precursors,GGPP and 10-deacetylbaccatin III,in cultivated species was 1.94 times(p 0.05)<and 1.71 times(p 0.01)higher than in wild species,respectively.Transcriptomic analysis identified 2606 differentially<expressed genes(DEGs),among which key enzyme genes related to paclitaxel biosynthesis(such as DXS,DXR,GGPS,etc.)were generally upregulated in cultivated species.Multiple key enzyme genes in both the 2-C-methyl-D-erythritol 4-phosphate pathway(MEP)and paclitaxel biosynthesis pathways were significantly upregulated in cultivated species.Conversely,genes and metabolites related to sugar metabolism were found to be higher in content in wild species.These findings reveal the significant advantage of cultivated species in paclitaxel production capacity,providing new insights into the metabolic regulation mechanisms during yew domestication.This has important implications for optimizing paclitaxel biosynthesis and guiding future improvements in T.cuspidata cultivars.
基金the"Qin Medicine"Quality Evaluation and Resource Development Discipline Innovation Team Project of Shaanxi University of Traditional Chinese Medicine(2019-QN01)Shaanxi University of Traditional Chinese Medicine School of Pharmacy/Shaanxi Engineering Research Centre for the Application and Development of Qinling Herbal Medicine,"Qin Medicine"Research and Development Key Laboratory(2019-QYPT-002)+2 种基金Shaanxi Provincial Administration of Traditional Chinese Medicine Province,Research and Development Key Laboratory(2019-QYPT-002)Shaanxi Provincial Administration of Traditional Chinese Medicine Province Chinese medicine province-wide earmarked special project:"Qin medicine planting and breeding guide research"(2021-QYZL-02)Shaanxi Provincial Science and Technology Department project:Chinese medicine Scutellaria baicalensis germplasm selection,seedling breeding and planting key technology research(2016KTTSSF01-01-01)and other projects.
文摘Background:In this research,we explored the operational principles of Huangqin Shegan decoction(HQSGD)for addressing acute pneumonia utilizing network pharmacology(NP)and transcriptomic analysis.Methods:Methods:A rat model of acute pneumonia was developed by treating rats with lipopolysaccharide(LPS)through a non-exposed tracheal drip.The pharmacological effects of HQSGD were evaluated via histopathological analysis of rat lung tissues,histological scoring of lung injury,assessment of lung index,serum inflammatory factors,oxidative stress levels,western blotting,and qRT-PCR.The active compounds of HQSGD were detected utilizing ultra-performance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS).NP and transcriptomic analysis were integrated to determine signaling pathways implicated in the pharmacological activity of HQSGD.The expression levels of mRNA and protein for factors implicated in these pathways were evaluated in rat lung tissues via qRT-PCR and western blotting,respectively.Results:HQSGD alleviated acute pneumonia in rats by reducing the lung index and the levels of TNF-α,IL-1β,CRP,and MDA while increasing the levels of SOD.The UPLC-MS/MS and NP techniques facilitated the identification of 28 bioactive constituents present in HQSGD.The principal 20 KEGG pathways were identified by intersecting the targets of HQSGD with pneumonia-related targets.These pathways were screened by comparing the transcriptomic data of the blank and model cohorts and those of the model and drug administration cohorts.GO and KEGG analyses indicated that the PI3K/AKT/NF-κB pathway was a potentially effective target of HQSGD.Conclusion:This investigation revealed the overall multi-component,multi-target,and multi-pathway interactions of HQSGD in the treatment of acute pneumonia.
基金supported by the National Key Research and Development Program (2022YEF0203200)National Science and Technology Innovation 2030 Major Program (STI2030-2021ZD0200100)National Key Research and Development Program (2018YFA0801400,2021YFA0805100)。
文摘The amniote pallium,a vital component of the forebrain,exhibits considerable evolutionary divergence across species and mediates diverse functions,including sensory processing,memory formation,and learning.However,the relationships among pallial subregions in different species remain poorly characterized,particularly regarding the identification of homologous neurons and their transcriptional signatures.In this study,we utilized singlenucleus RNA sequencing to examine over 130?000 nuclei from the macaque(Macaca fascicularis)neocortex,complemented by datasets from humans(Homo sapiens),mice(Mus musculus),zebra finches(Taeniopygia guttata),turtles(Chrysemys picta bellii),and lizards(Pogona vitticeps),enablingcomprehensivecross-species comparison.Results revealed transcriptomic conservation and species-specific distinctions within the amniote pallium.Notable similarities were observed among cell subtypes,particularly within PVALB+inhibitory neurons,which exhibited species-preferred subtypes.Furthermore,correlations between pallial subregions and several transcription factor candidates were identified,including RARB,DLX2,STAT6,NR3C1,and THRB,with potential regulatory roles in gene expression in mammalian pallial neurons compared to their avian and reptilian counterparts.These results highlight the conserved nature of inhibitory neurons,remarkable regional divergence of excitatory neurons,and species-specific gene expression and regulation in amniote pallial neurons.Collectively,these findings provide valuable insights into the evolutionary dynamics of the amniote pallium.
基金supported by the National Natural Science Foundation of China(No.82374158)National Science and Technology Major Project(No.2018ZX09711001-002-004)+1 种基金the Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program(No.CXTD22007)the Medical and Health Technology Innovation Project(No.2022-I2M-1-020).
文摘A comprehensive understanding of the molecular details at spatial levels within heterogeneous cardiac tissue in heart failure(HF)is paramount for enhancing our knowledge of the pathophysiology of HF and pinpointing potential therapeutic targets.Here,we present an analytical strategy for the deep discovery of heterogeneous metabolism and drug response in the heart tissue of rats with HF using airflow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)coupled with bulk RNAsequencing.Spatial metabolomics illustrated pronounced metabolic heterogeneity between the infarct(I),infarct margin(IM),and non-infarct(NI)areas of heart tissue in HF.Integrated transcriptomics showed that increased mRNA expression of ATP citrate lyase disrupted the tricarboxylic acid(TCA)cycle in the NI area.Impairment of the carnitine shuttle system led to a significant accumulation of carnitines,suggesting potential abnormalities in fatty acid(FA)oxidation.Coupling on-tissue chemical derivatization with AFADESI-MSI enabled us to confirm the occurrence of incomplete oxidation of FAs in the NI area.Additionally,we observed a heterogeneous drug response between the anti-HF medications valsartan and Qishen Yiqi Dripping Pills(QDP).Valsartan exhibited a more pronounced effect on metabolic regulation in the I area,whereas QDP exerted stronger regulatory effects on metabolism in the NI area.Utilizing this method,four potential therapeutic targets were identified in HF:CPT1A,PDHB,ACLY,and BCAT2,which were preliminarily validated by western blotting.Overall,integrating spatial metabolomics with transcriptomics facilitates comprehensive analyses that link differential metabolites and genes,enabling a more precise characterization of metabolic changes in heart injury microareas and providing effective methods for elucidating molecular mechanisms and identifying potential therapeutic targets for HF.
基金supported by the National Natural Science Foundation of China(32222079 to L.J.and 32202621 to D.D.W.)。
文摘Pigs have emerged as valuable large-animal models for cardiac xenotransplantation;however,the temporal dynamics of myocardial development in this species remains insufficiently defined.This study analyzed gene expression patterns across four key developmental stages(neonatal,juvenile,sexual maturity,and adulthood)to delineate the molecular mechanisms driving porcine myocardial development.Increases in heart weight were accompanied by proportional expansion of myocardial fiber area and chamber size,reflecting coordinated structural development.Transcriptomic profiling of myocardial tissue by RNA sequencing(RNA-seq)identified 2189 differentially expressed genes(DEGs)across stage comparisons.Short time-series expression miner(STEM)analysis classified these DEGs into four major expression clusters enriched in pathways associated with myocardial development,immune responses,cell proliferation,and metabolic processes.Among 359 DEGs conserved across all developmental stages,six candidate genes were strongly associated with myocardial development.Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)confirmed a significant correlation between the expression of these candidate genes and myocardial development in porcine tissue.These findings establish a transcriptomic framework for porcine myocardial maturation and provide a molecular basis for advancing cardiac xenotransplantation.
基金supported by the Northeast Asia Biodiversity Research Center(grant number 411147021003).
文摘The predominant causal agent of poplar leaf blight is the pathogenic fungus Alternaria alternata (Fr.) Keissl., which exhibits host specificity toward Populus species. To elucidate the molecular response mechanisms of A. alternata under fludioxonil fungicide stress, the fungus was cultured at the half-maximal effective concentration (EC₅₀) of fludioxonil. Transcriptomic and metabolomic profiles were analyzed using mycelia harvested under these conditions. Comparative analysis revealed 1,001 differentially expressed genes (DEGs) in the resistant strain (RS) relative to the wild-type strain (WT), comprising 628 upregulated and 373 downregulated genes. Concurrently, 524 differentially accumulated metabolites (DAMs) were identified, with 336 upregulated and 188 downregulated metabolites. KEGG pathway enrichment demonstrated pronounced upregulation in glycerophospholipid metabolism, α-linolenic acid metabolism, nucleic acid biosynthesis, and glycosylation processes. Conversely, arachidonic acid and galactose metabolism pathways were suppressed. Significant downregulation was observed in phosphatidylinositol signaling, aflatoxin biosynthesis, and cutin/suberin/wax biosynthesis pathways. Transcriptomic profiling further indicated that upregulated DEGs were predominantly associated with amino sugar/nucleotide sugar metabolism, ABC transporters, aflatoxin biosynthesis, and purine metabolism, while downregulated DEGs were enriched in N-glycan biosynthesis, endoplasmic reticulum protein processing, steroid biosynthesis, and riboflavin metabolism. Fludioxonil exerted substantial inhibitory effects on fungal growth, pathogenicity, and metabolic activity. Mechanistically, A. alternata counteracted fungicide-induced stress through modulation of its antioxidant defense system. This integrative multi-omics study delineates the dynamic gene expression and metabolic reprogramming in A. alternata under fludioxonil exposure, providing novel insights into potential molecular targets and informing the development of next-generation fungicidal strategies for phytopathogen control.
