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
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
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
Litchi chinensis Sonn.is an important economic fruit tree in tropical and subtropical regions.Regrettably,the efficiency of plant regeneration via somatic embryogenesis in litchi is typically low due to the poor conve...Litchi chinensis Sonn.is an important economic fruit tree in tropical and subtropical regions.Regrettably,the efficiency of plant regeneration via somatic embryogenesis in litchi is typically low due to the poor conversion of embryos to plants.The purpose of this study was to establish a regeneration system via somatic embryogenesis from immature embryos explants in‘Heiye'cultivar of litchi.Our results demonstrated that MS medium supplemented with 2.0 mg L^(-1)2,4-D was optimal for callus induction.For somatic embryo(SE)induction,MS medium containing0.5 g L^(-1) activated charcoal(AC)was the most effective,while the use of zeatin(ZT)and thidiazuron(TDZ)resulted in abnormal somatic embryos.The rooting and regeneration rate of 2.15%and 17.5%,respectively,were achieved using MS medium supplemented with 0.5 g L^(-1) AC.Furthermore,transcriptome analysis was performed on embryogenic callus(EC),globular embryo(GE),and heart embryo(HE)to explore the molecular mechanisms of early somatic embryogenesis.2,587 common differentially expressed genes(DEGs)between EC_vs_GE and EC_vs_HE were identified,and the expression patterns of these common DEGs were separated into twelve major clusters.GO annotation and KEGG pathway analysis revealed that these common DEGs were implicated in plant hormone signal transduction,auxin-activated signaling pathway,and other biological processes.Additionally,differentially expressed transcription factors were identified,and the function of LcBBM2 which is specifically highly expressed during early somatic embryogenesis was verified.Overexpression of LcBBM2 in tomato promotes callus and shoot formation.Therefore,this study can provide a theoretical basis and technical support for genetic breeding improvement of litchi.展开更多
Ascorbic acid, also referred to as vitamin C(Vc), is an important nutrient found in fruits and vegetables that promotes produce quality and human health. Rosa roxburghii is an underutilized natural fruit that contains...Ascorbic acid, also referred to as vitamin C(Vc), is an important nutrient found in fruits and vegetables that promotes produce quality and human health. Rosa roxburghii is an underutilized natural fruit that contains very high levels of Vc. However, the Vc content of R. roxburghii varies considerably during plant development and ripening. To better understand the molecular mechanisms that underlie fluctuations in Vc content of R. roxburghii fruit at different developmental stages, we performed transcriptomic and metabolomic analyses and identified two significant gene networks/modules and 168 transcription factors directly involved in Vc synthesis. Promoter analysis of two core genes involved in Vc synthesis, RrGGP and RrGalUR, revealed the presence of a retroviral long terminal repeat(LTR) insert in the RrGalUR promoter. Using yeast one-hybrid and dual-luciferase assays, we demonstrated that the transcription factors RrHY5H and RrZIP9 bind to the promoter of RrGGP to promote its expression. RrZIP6 and RrWRKY4 bind to the LTR in the RrGalUR promoter to promote its expression. Our results reveal a molecular mechanism that controls Vc synthesis and accumulation in R. roxburghii fruit.展开更多
Tomato is an important economic crop all over the world.Volatile flavors in tomato fruit are key factors influencing consumer liking and commercial quality.However,the regulatory mechanism controlling the volatile fla...Tomato is an important economic crop all over the world.Volatile flavors in tomato fruit are key factors influencing consumer liking and commercial quality.However,the regulatory mechanism controlling the volatile flavors of tomatoes is still not clear.Here,we integrated the metabolome and transcriptome of the volatile flavors in tomato fruit to explore the regulatory mechanism of volatile flavor formation,using wild and cultivated tomatoes with significant differences in flavors.A total of 35 volatile flavor compounds were identified,based on the solid phase microextraction-gas chromatography-mass spectrometry(SPME-GC-MS).The content of the volatiles,affecting fruit flavor,significantly increased in the transition from breaker to red ripe fruit stage.Moreover,the total content of the volatiles in wild tomatoes was much higher than that in the cultivated tomatoes.The content variations of all volatile flavors were clustered into 10 groups by hierarchical cluster and Pearson coefficient correlation(PCC)analysis.The fruit transcriptome was also patterned into 10 groups,with significant variations both from the mature green to breaker fruit stage and from the breaker to red ripe fruit stage.Combining the metabolome and the transcriptome of the same developmental stage of fruits by co-expression analysis,we found that the expression level of 1182 genes was highly correlated with the content of volatile flavor compounds,thereby constructing two regulatory pathways of important volatile flavors.One pathway is tetrahydrothiazolidine N-hydroxylase(SlTNH1)-dependent,which is regulated by two transcription factors(TFs)from the bHLH and AP2/ERF families,controlling the synthesis of 2-isobutylthiazole in amino acid metabolism.The other is lipoxygenase(Sl LOX)-dependent,which is regulated by one TF from the HD-Zip family,controlling the synthesis of hexanal and(Z)-2-heptenal in fatty acid metabolism.Dual-luciferase assay confirmed the binding of b HLH and AP2/ERF to their structural genes.The findings of this study provide new insights into volatile flavor formation in tomato fruit,which can be useful for tomato flavor improvement.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
Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.Howev...Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.However,the molecular mechanisms by which exogenous Spd application alleviates waterlogging stress remain unclear.This study employed physiological analysis and multi-omics approaches to investigate the effect of Spd application on waterlogging stress.The application of Spd enhanced the expression of genes related to light-harvesting complex(LHC),photosynthesis,and starch-related pathways,while inhibiting chlorophyll degradation and maintaining higher photosynthetic rates,thereby increasing biomass accumulation under waterlogging stress.The activation of genes associated with trehalose and Spd biosynthesis resulted in elevated accumulation of trehalose and endogenous Spd.The inhibition of 1-aminocyclopropane-1-carboxylic acid(ACC)oxidase(ACO)expression contributed to reduced ethylene emission,enhancing maize resistance to waterlogging.Following Spd application,auxin-related genes were up-regulated and indole acetic acid(IAA)content increased,promoting cell elongation in maize and maintaining normal growth under waterlogging stress.Additionally,the upregulation of lipid-related genes led to increased lipid content,protecting cell membranes under waterlogging conditions.These molecular and physiological modifications collectively enhanced resistance to waterlogging stress.These findings advance our understanding of Spd's regulatory roles in mitigating waterlogging damage and provide valuable insights for breeding waterlogging-tolerant maize varieties.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
Perchlorate(ClO_(4)^(−))is a type of novel persistent inorganic pollutant that has gained increasing attention because of its high solubility,poor degradability,and widespread distribution.However,the impacts of perch...Perchlorate(ClO_(4)^(−))is a type of novel persistent inorganic pollutant that has gained increasing attention because of its high solubility,poor degradability,and widespread distribution.However,the impacts of perchlorate on aquatic autotrophs such cyanobacterium are still unclear.Herein,Synechocystis sp.PCC6803(Synechocystis)was used to investigate the response mechanisms of perchlorate on cyanobacterium by integrating physiological and transcriptome analyses.Physiological results showed that perchlorate mainly damaged the photosystem of Synechocystis,and the inhibition degree of photosystem II(PSII)was severer than that of photosystem I(PSI).When the exposed cells were moved to a clean medium,the photosynthetic activities were slightly repaired but still lower than in the control group,indicating irreversible damage.Furthermore,perchlorate also destroyed the cellular ultrastructure and induced oxidative stress in Synechocystis.The antioxidant glutathione(GSH)content and the superoxide dismutase(SOD)enzyme activity were enhanced to scavenge harmful reactive oxygen(ROS)in Synechocystis.Transcriptome analysis revealed that the genes associated with“photosynthesis”and“electron transport”were significantly regulated.For instance,most genes related to PSI(e.g.,psaf,psaJ)and the“electron transport chain”were upregulated,whereas most genes related to PSII(e.g.,psbA3,psbD1,psbB,and psbC)were downregulated.Additionally,perchlorate also induced the expression of genes related to the antioxidant system(sod2,gpx,gst,katG,and gshB)to reduce oxidative damage.Overall,this study is the first to investigate the impacts andmechanisms of cyanobacterium under perchlorate stress,which is conducive to assessing the risk of perchlorate in aquatic environments.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
Hawthorn(Crataegus pinnatifida)fruit peel color and seed hardness are key traits that significantly impact economic value.We present here the high-quality chromosome-scale genomes of two cultivars,including the hard-s...Hawthorn(Crataegus pinnatifida)fruit peel color and seed hardness are key traits that significantly impact economic value.We present here the high-quality chromosome-scale genomes of two cultivars,including the hard-seed,yellow-peel C.pinnatifida“Jinruyi”(JRY)and the soft-seed,red-peel C.pinnatifida“Ruanzi”(RZ).The assembled genomes comprising 17 chromosomes are 809.1 Mb and 760.5 Mb in size,achieving scaffold N50 values of 48.5 Mb and 46.8 Mb for JRY and RZ,respectively.Comparative genomic analysis identifies 3.6–3.8 million single nucleotide polymorphisms,8.5–9.3 million insertions/deletions,and approximately 30 Mb of presence/absence variations across different hawthorn genomes.Through integrating differentially expressed genes and accumulated metabolites,we filter candidate genes CpMYB114 and CpMYB44 associated with differences in hawthorn fruit peel color and seed hardness,respectively.Functional validation confirms that CpMYB114-CpANS regulates anthocyanin biosynthesis in hawthorn peels,contributing to the observed variation in peel color.CpMYB44-CpCOMT is significantly upregulated in JRY and has been shown to promote lignin biosynthesis,resulting in the distinction in seed hardness.Overall,this study reveals new insights into understanding of distinct peel pigmentation and seed hardness in hawthorn and provides an abundant resource for molecular breeding.展开更多
Nitrogen(N)is a limiting factor that determines the yield and quality of chrysanthemum.Genetic variation in N use efficiency(NUE)has been reported among chrysanthemum genotypes.We performed a transcriptome analysis of...Nitrogen(N)is a limiting factor that determines the yield and quality of chrysanthemum.Genetic variation in N use efficiency(NUE)has been reported among chrysanthemum genotypes.We performed a transcriptome analysis of two chrysanthemum genotypes,'Nannonglihuang'(LH,N-efficient genotype)and'Nannongxuefeng"(XF,N-inefficient genotype),under low N(0.4 mmol L^(-1)N)and normal N(8 mmol L^(-1)N)treatments for 15 d and an N recovery treatment for 12 h(low N treatment for 15 d and then normal N treatment for 12 h)to understand the genetic factors impacting NUE in chrysanthemum.The two genotypes exhibited contrasting responses to the different N treatments.The N-efficient genotype LH had significant superiority in agronomic traits,N accumulation and glutamine synthase activity under both normal N and low N treatments.Low N treatment promoted root growth in LH,but inhibited root growth in XF.Transcriptome analysis revealed that the low N treatment increased the expression of some N metabolism genes,genes related to auxin and abscisic acid signal transduction in the roots of both genotypes,as well as genes related to gibberellin signal transduction in roots of LH.The N recovery treatment just increased the expression of genes related to cytokinin signal transduction in roots of LH.The expression levels of the NRT2.1,AMT1.1,and Gln1 genes related to gibberellin and cytokinin signal transduction were higher in roots of LH than in XF under different N treatments,suggesting that the genes related to N metabolism and hormone(auxin,abscisic acid,gibberellin,and cytokinin)signal transduction in roots of LH are more sensitive to different N treatments than those of XF.Co-expression network analysis(WGCNA)also identified hub genes like bZIP43,bHLH93,NPF6.3,IBR10,MYB62,PP2C,PP2C06 and NLP7,which may be the key regulators of N-mediated responses in chrysanthemum and play crucial roles in enhancing NUE and resistance to low N stress in the N-efficient chrysanthemum genotype.These results revealed the key factors involved in regulating NUE in chrysanthemum at the genetic level,which provides new insights into the complex mechanism of efficient nitrogen utilization in chrysanthemum,and can be useful for the improvement and breeding of high NUE chrysanthemum genotypes.展开更多
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.
基金supported by the National Natural Science Fund of China(Grant Nos.31872066 and 32272663)the Science and Technology Planning Project of Guangzhou(Grant No.2023B01J2002)+1 种基金the Key Research and Development Program of Hainan(Grant No.ZDYF2023XDNY052)the Seed Industry Engineering Project of Ministry of Agriculture and Rural Affairs of Guangdong(Grant Nos.2022-NPY-00-004 and 2022-NBH-00-001)。
文摘Litchi chinensis Sonn.is an important economic fruit tree in tropical and subtropical regions.Regrettably,the efficiency of plant regeneration via somatic embryogenesis in litchi is typically low due to the poor conversion of embryos to plants.The purpose of this study was to establish a regeneration system via somatic embryogenesis from immature embryos explants in‘Heiye'cultivar of litchi.Our results demonstrated that MS medium supplemented with 2.0 mg L^(-1)2,4-D was optimal for callus induction.For somatic embryo(SE)induction,MS medium containing0.5 g L^(-1) activated charcoal(AC)was the most effective,while the use of zeatin(ZT)and thidiazuron(TDZ)resulted in abnormal somatic embryos.The rooting and regeneration rate of 2.15%and 17.5%,respectively,were achieved using MS medium supplemented with 0.5 g L^(-1) AC.Furthermore,transcriptome analysis was performed on embryogenic callus(EC),globular embryo(GE),and heart embryo(HE)to explore the molecular mechanisms of early somatic embryogenesis.2,587 common differentially expressed genes(DEGs)between EC_vs_GE and EC_vs_HE were identified,and the expression patterns of these common DEGs were separated into twelve major clusters.GO annotation and KEGG pathway analysis revealed that these common DEGs were implicated in plant hormone signal transduction,auxin-activated signaling pathway,and other biological processes.Additionally,differentially expressed transcription factors were identified,and the function of LcBBM2 which is specifically highly expressed during early somatic embryogenesis was verified.Overexpression of LcBBM2 in tomato promotes callus and shoot formation.Therefore,this study can provide a theoretical basis and technical support for genetic breeding improvement of litchi.
基金supported in part by the Priority Academic Program Development of Jiangsu Higher Education Institutions and the State Key Laboratory of Crop Genetics and Germplasm Enhancement (Grant No. ZW201813)supported by the high-performance computing platform at the Bioinformatics Center of Nanjing Agricultural University。
文摘Ascorbic acid, also referred to as vitamin C(Vc), is an important nutrient found in fruits and vegetables that promotes produce quality and human health. Rosa roxburghii is an underutilized natural fruit that contains very high levels of Vc. However, the Vc content of R. roxburghii varies considerably during plant development and ripening. To better understand the molecular mechanisms that underlie fluctuations in Vc content of R. roxburghii fruit at different developmental stages, we performed transcriptomic and metabolomic analyses and identified two significant gene networks/modules and 168 transcription factors directly involved in Vc synthesis. Promoter analysis of two core genes involved in Vc synthesis, RrGGP and RrGalUR, revealed the presence of a retroviral long terminal repeat(LTR) insert in the RrGalUR promoter. Using yeast one-hybrid and dual-luciferase assays, we demonstrated that the transcription factors RrHY5H and RrZIP9 bind to the promoter of RrGGP to promote its expression. RrZIP6 and RrWRKY4 bind to the LTR in the RrGalUR promoter to promote its expression. Our results reveal a molecular mechanism that controls Vc synthesis and accumulation in R. roxburghii fruit.
基金supported by the National Natural Science Foundation of China(Grant Nos.32120103010,32002050)Beijing Joint Research Program for Germplasm Innovation and New Variety Breeding(Grant No.G20220628003-03)the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences。
文摘Tomato is an important economic crop all over the world.Volatile flavors in tomato fruit are key factors influencing consumer liking and commercial quality.However,the regulatory mechanism controlling the volatile flavors of tomatoes is still not clear.Here,we integrated the metabolome and transcriptome of the volatile flavors in tomato fruit to explore the regulatory mechanism of volatile flavor formation,using wild and cultivated tomatoes with significant differences in flavors.A total of 35 volatile flavor compounds were identified,based on the solid phase microextraction-gas chromatography-mass spectrometry(SPME-GC-MS).The content of the volatiles,affecting fruit flavor,significantly increased in the transition from breaker to red ripe fruit stage.Moreover,the total content of the volatiles in wild tomatoes was much higher than that in the cultivated tomatoes.The content variations of all volatile flavors were clustered into 10 groups by hierarchical cluster and Pearson coefficient correlation(PCC)analysis.The fruit transcriptome was also patterned into 10 groups,with significant variations both from the mature green to breaker fruit stage and from the breaker to red ripe fruit stage.Combining the metabolome and the transcriptome of the same developmental stage of fruits by co-expression analysis,we found that the expression level of 1182 genes was highly correlated with the content of volatile flavor compounds,thereby constructing two regulatory pathways of important volatile flavors.One pathway is tetrahydrothiazolidine N-hydroxylase(SlTNH1)-dependent,which is regulated by two transcription factors(TFs)from the bHLH and AP2/ERF families,controlling the synthesis of 2-isobutylthiazole in amino acid metabolism.The other is lipoxygenase(Sl LOX)-dependent,which is regulated by one TF from the HD-Zip family,controlling the synthesis of hexanal and(Z)-2-heptenal in fatty acid metabolism.Dual-luciferase assay confirmed the binding of b HLH and AP2/ERF to their structural genes.The findings of this study provide new insights into volatile flavor formation in tomato fruit,which can be useful for tomato flavor improvement.
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-02-20)the Henan Province Agro-ecosystem Field Observation and Research Station,China(30602535)。
文摘Waterlogging stress significantly impairs plant growth and reduces crop yields.Spermidine(Spd),functioning as a second messenger,demonstrates positive effects on plant growth under waterlogging stress conditions.However,the molecular mechanisms by which exogenous Spd application alleviates waterlogging stress remain unclear.This study employed physiological analysis and multi-omics approaches to investigate the effect of Spd application on waterlogging stress.The application of Spd enhanced the expression of genes related to light-harvesting complex(LHC),photosynthesis,and starch-related pathways,while inhibiting chlorophyll degradation and maintaining higher photosynthetic rates,thereby increasing biomass accumulation under waterlogging stress.The activation of genes associated with trehalose and Spd biosynthesis resulted in elevated accumulation of trehalose and endogenous Spd.The inhibition of 1-aminocyclopropane-1-carboxylic acid(ACC)oxidase(ACO)expression contributed to reduced ethylene emission,enhancing maize resistance to waterlogging.Following Spd application,auxin-related genes were up-regulated and indole acetic acid(IAA)content increased,promoting cell elongation in maize and maintaining normal growth under waterlogging stress.Additionally,the upregulation of lipid-related genes led to increased lipid content,protecting cell membranes under waterlogging conditions.These molecular and physiological modifications collectively enhanced resistance to waterlogging stress.These findings advance our understanding of Spd's regulatory roles in mitigating waterlogging damage and provide valuable insights for breeding waterlogging-tolerant maize varieties.
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 Project of Chinese Manned Spaceflight(No.YYWT-0801-EXP-09)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA17010502)Jiangsu Province Ecological Environment Scientific Research Project(No.2022008).
文摘Perchlorate(ClO_(4)^(−))is a type of novel persistent inorganic pollutant that has gained increasing attention because of its high solubility,poor degradability,and widespread distribution.However,the impacts of perchlorate on aquatic autotrophs such cyanobacterium are still unclear.Herein,Synechocystis sp.PCC6803(Synechocystis)was used to investigate the response mechanisms of perchlorate on cyanobacterium by integrating physiological and transcriptome analyses.Physiological results showed that perchlorate mainly damaged the photosystem of Synechocystis,and the inhibition degree of photosystem II(PSII)was severer than that of photosystem I(PSI).When the exposed cells were moved to a clean medium,the photosynthetic activities were slightly repaired but still lower than in the control group,indicating irreversible damage.Furthermore,perchlorate also destroyed the cellular ultrastructure and induced oxidative stress in Synechocystis.The antioxidant glutathione(GSH)content and the superoxide dismutase(SOD)enzyme activity were enhanced to scavenge harmful reactive oxygen(ROS)in Synechocystis.Transcriptome analysis revealed that the genes associated with“photosynthesis”and“electron transport”were significantly regulated.For instance,most genes related to PSI(e.g.,psaf,psaJ)and the“electron transport chain”were upregulated,whereas most genes related to PSII(e.g.,psbA3,psbD1,psbB,and psbC)were downregulated.Additionally,perchlorate also induced the expression of genes related to the antioxidant system(sod2,gpx,gst,katG,and gshB)to reduce oxidative damage.Overall,this study is the first to investigate the impacts andmechanisms of cyanobacterium under perchlorate stress,which is conducive to assessing the risk of perchlorate in aquatic environments.
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 Natural Science Foundation of China(32401631)Beijing Academy of Agriculture and Forestry Science Innovation Capability Construction Special Project(KJCX20251401)+1 种基金Research Fund for Youth of Beijing Academy of Agricultural and Forestry Science(QNJJ202409)Youth Research Foundation of Institute of Forestry and Pomology,Beijing Academy of Agriculture and Forestry Science(LGSJJ202302).
文摘Hawthorn(Crataegus pinnatifida)fruit peel color and seed hardness are key traits that significantly impact economic value.We present here the high-quality chromosome-scale genomes of two cultivars,including the hard-seed,yellow-peel C.pinnatifida“Jinruyi”(JRY)and the soft-seed,red-peel C.pinnatifida“Ruanzi”(RZ).The assembled genomes comprising 17 chromosomes are 809.1 Mb and 760.5 Mb in size,achieving scaffold N50 values of 48.5 Mb and 46.8 Mb for JRY and RZ,respectively.Comparative genomic analysis identifies 3.6–3.8 million single nucleotide polymorphisms,8.5–9.3 million insertions/deletions,and approximately 30 Mb of presence/absence variations across different hawthorn genomes.Through integrating differentially expressed genes and accumulated metabolites,we filter candidate genes CpMYB114 and CpMYB44 associated with differences in hawthorn fruit peel color and seed hardness,respectively.Functional validation confirms that CpMYB114-CpANS regulates anthocyanin biosynthesis in hawthorn peels,contributing to the observed variation in peel color.CpMYB44-CpCOMT is significantly upregulated in JRY and has been shown to promote lignin biosynthesis,resulting in the distinction in seed hardness.Overall,this study reveals new insights into understanding of distinct peel pigmentation and seed hardness in hawthorn and provides an abundant resource for molecular breeding.
基金supported by the National Key R&D Programof China(2020YFD1000400)the National Natural Science Foundation of China(32072603)+1 种基金the Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(21)2004)the JBGS Project of Seed Industry Revitalization in Jiangsu Province,China(JBGS[2021]020).
文摘Nitrogen(N)is a limiting factor that determines the yield and quality of chrysanthemum.Genetic variation in N use efficiency(NUE)has been reported among chrysanthemum genotypes.We performed a transcriptome analysis of two chrysanthemum genotypes,'Nannonglihuang'(LH,N-efficient genotype)and'Nannongxuefeng"(XF,N-inefficient genotype),under low N(0.4 mmol L^(-1)N)and normal N(8 mmol L^(-1)N)treatments for 15 d and an N recovery treatment for 12 h(low N treatment for 15 d and then normal N treatment for 12 h)to understand the genetic factors impacting NUE in chrysanthemum.The two genotypes exhibited contrasting responses to the different N treatments.The N-efficient genotype LH had significant superiority in agronomic traits,N accumulation and glutamine synthase activity under both normal N and low N treatments.Low N treatment promoted root growth in LH,but inhibited root growth in XF.Transcriptome analysis revealed that the low N treatment increased the expression of some N metabolism genes,genes related to auxin and abscisic acid signal transduction in the roots of both genotypes,as well as genes related to gibberellin signal transduction in roots of LH.The N recovery treatment just increased the expression of genes related to cytokinin signal transduction in roots of LH.The expression levels of the NRT2.1,AMT1.1,and Gln1 genes related to gibberellin and cytokinin signal transduction were higher in roots of LH than in XF under different N treatments,suggesting that the genes related to N metabolism and hormone(auxin,abscisic acid,gibberellin,and cytokinin)signal transduction in roots of LH are more sensitive to different N treatments than those of XF.Co-expression network analysis(WGCNA)also identified hub genes like bZIP43,bHLH93,NPF6.3,IBR10,MYB62,PP2C,PP2C06 and NLP7,which may be the key regulators of N-mediated responses in chrysanthemum and play crucial roles in enhancing NUE and resistance to low N stress in the N-efficient chrysanthemum genotype.These results revealed the key factors involved in regulating NUE in chrysanthemum at the genetic level,which provides new insights into the complex mechanism of efficient nitrogen utilization in chrysanthemum,and can be useful for the improvement and breeding of high NUE chrysanthemum genotypes.
