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
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
Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECK...Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.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
While bulk RNA sequencing and single-cell RNA sequencing have shed light on cellular heterogeneity and potential molecular mechanisms in the musculoskeletal system in both physiological and various pathological states...While bulk RNA sequencing and single-cell RNA sequencing have shed light on cellular heterogeneity and potential molecular mechanisms in the musculoskeletal system in both physiological and various pathological states,the spatial localization of cells and molecules and intercellular interactions within the tissue context require further elucidation.Spatial transcriptomics has revolutionized biological research by simultaneously capturing gene expression profiles and in situ spatial information of tissues,gradually finding applications in musculoskeletal research.This review provides a summary of recent advances in spatial transcriptomics and its application to the musculoskeletal system.The classification and characteristics of data acquisition techniques in spatial transcriptomics are briefly outlined,with an emphasis on widely-adopted representative technologies and the latest technological breakthroughs,accompanied by a concise workflow for incorporating spatial transcriptomics into musculoskeletal system research.The role of spatial transcriptomics in revealing physiological mechanisms of the musculoskeletal system,particularly during developmental processes,is thoroughly summarized.Furthermore,recent discoveries and achievements of this emerging omics tool in addressing inflammatory,traumatic,degenerative,and tumorous diseases of the musculoskeletal system are compiled.Finally,challenges and potential future directions for spatial transcriptomics,both as a field and in its applications in the musculoskeletal system,are discussed.展开更多
Spatial transcriptomics technology provides novel insights into the spatial organization of gene expression during embryonic development.In this study,we propose a method that integrates analysis across both temporal ...Spatial transcriptomics technology provides novel insights into the spatial organization of gene expression during embryonic development.In this study,we propose a method that integrates analysis across both temporal and spatial dimensions to investigate spatial transcriptomics data from mouse embryos at different developmental stages.We quantified the spatial expression pattern of each gene at various stages by calculating its Moran’s I.Furthermore,by employing time-series clustering to identify dynamic co-expression modules,we identified several developmentally stage-specific regulatory gene modules.A key finding was the presence of distinct,stage-specific gene network modules across different developmental periods:Early modules focused on morphogenesis,mid-stage on organ development,and late-stage on neural and tissue maturation.Functional enrichment analysis further confirmed the core biological functions of each module.The dynamic,spatially-resolved gene expression model constructed in this study not only provides new biological insights into the programmed spatiotemporal reorganization of gene regulatory networks during embryonic development but also presents an effective approach for analyzing complex spatiotemporal omics data.This work provides a new perspective for understanding developmental biology,regenerative medicine,and related fields.展开更多
Recent advances in spatially resolved transcriptomics(SRT)have provided new opportunities for characterizing spatial structures of various tissues.Graph-based geometric deep learning has gained widespread adoption for...Recent advances in spatially resolved transcriptomics(SRT)have provided new opportunities for characterizing spatial structures of various tissues.Graph-based geometric deep learning has gained widespread adoption for spatial domain identification tasks.Currently,most methods define adjacency relation between cells or spots by their spatial distance in SRT data,which overlooks key biological interactions like gene expression similarities,and leads to inaccuracies in spatial domain identification.To tackle this challenge,we propose a novel method,SpaGRA(https://github.com/sunxue-yy/SpaGRA),for automatic multi-relationship construction based on graph augmentation.SpaGRA uses spatial distance as prior knowledge and dynamically adjusts edge weights with multi-head graph attention networks(GATs).This helps SpaGRA to uncover diverse node relationships and enhance message passing in geometric contrastive learning.Additionally,SpaGRA uses these multi-view relationships to construct negative samples,addressing sampling bias posed by random selection.Experimental results show that SpaGRA presents superior domain identification performance on multiple datasets generated from different protocols.Using SpaGRA,we analyze the functional regions in the mouse hypothalamus,identify key genes related to heart development in mouse embryos,and observe cancer-associated fibroblasts enveloping cancer cells in the latest Visium HD data.Overall,SpaGRA can effectively characterize spatial structures across diverse SRT datasets.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
[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
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
Background Clostridium perfringens is a pathogen that secretes multiple toxins,impacting humans and animals.It can cause intestinal diseases such as necrotic enteritis.Although tannins inhibit C.perfringens proliferat...Background Clostridium perfringens is a pathogen that secretes multiple toxins,impacting humans and animals.It can cause intestinal diseases such as necrotic enteritis.Although tannins inhibit C.perfringens proliferation,the precise underlying mechanisms are unclear.Objective This study integrated transcriptomics and metabolomics to systematically investigate the mechanism by which tannins,specifically pentagalloylglucose(PGG)and tannic acid(TA),inhibit C.perfringens and potential pathways to alleviate infection in vivo.Results Ion concentration measurements,flow cytometric analysis,and transmission electron microscopy revealed that PGG and TA damaged the cell membrane structure of C.perfringens,triggering cytoplasmic content leakage.Additionally,PGG and TA significantly affected C.perfringens at the transcriptional and metabolic levels.Bioinformatics analysis revealed that PGG and TA induced amino acid restriction,disrupted energy metabolism,and impeded the ability of C.perfringens to sense and respond to the external environment.In an in vitro C.perfringens-infected intestinal cell model,PGG and TA boundαtoxin,significantly reduced the mRNA expression of inflammatory factors,and improved intestinal barrier function and cell viability.Compared to PGG,TA exhibited stronger inhibitory activity against C.perfringens and binding toαtoxin.In vivo,PGG and TA alleviated C.perfringens-induced weight loss in mice,improved intestinal villi morphology,and reduced intestinal inflammation and tight junction gene dysregulation.Conclusion These findings indicate that tannins inhibit C.perfringens,improve gut tissue integrity and reduce inflammation,demonstrating their multi-target effects of resisting intestinal diseases caused by harmful bacteria.This offers new insights for plant polyphenol-based strategies against necrotic enteritis.展开更多
Commercial cultivars of garlic,a popular condiment,are sterile,making genetic variation and germplasm innovation of this plant challenging.Understanding mechanism of gamete sterility in garlic and their key regulatory...Commercial cultivars of garlic,a popular condiment,are sterile,making genetic variation and germplasm innovation of this plant challenging.Understanding mechanism of gamete sterility in garlic and their key regulatory networks is therefore important for fertility restoration.In this work,we conducted a detailed phenotypic analysis of fertile and sterile garlic genotypes and found that enlargement of topset in the inflorescence of sterile genotypes led to abnormal flowers.Additional cytological observations showed that aberrant meiotic cytokinesis in sterile garlic ultimately resulted in pollen degeneration.Transcriptomics analysis of sterile and fertile genotypes identified possible molecular mechanisms underlying gamete abortion.A total of 100710 differentially expressed genes(DEGs)between the fertile and sterile garlic flowers at three stages of gamete development were identified,many of which were involved in homologous chromosome synapsis during meiosis,MYB transcription factor regulation,ribosome biogenesis and plant hormone signal transduction.Taken together,these results provide insight into the molecular mechanisms and regulatory networks underlying gamete development in garlic and point to a set of candidate genes for further functional characterization.展开更多
Wheat stripe rust,a devastating disease caused by the fungal pathogen Puccinia striiformis f.sp.tritici(Pst),poses a significant threat to global wheat production.Growing resistant cultivars is a crucial strategy for ...Wheat stripe rust,a devastating disease caused by the fungal pathogen Puccinia striiformis f.sp.tritici(Pst),poses a significant threat to global wheat production.Growing resistant cultivars is a crucial strategy for wheat stripe rust management.However,the underlying molecular mechanisms of wheat resistance to Pst remain incompletely understood.To unravel these mechanisms,we employed high-throughput RNA sequencing(RNA-Seq)to analyze the transcriptome of the resistant wheat cultivar Mianmai 46(MM46)at different time points(24,48,and 96 h)post-inoculation with the Pst race CYR33.The analysis revealed that Pst infection significantly altered the expression of genes involved in photosynthesis and energy metabolism,suggesting a disruption of host cellular processes.Conversely,the expression of several resistance genes was upregulated,indicating activation of defense responses.Further analysis identified transcription factors(TFs),pathogen-related(PR)proteins,and chitinase-encoding genes as key players in wheat resistance to Pst.These genes likely contribute to the activation of defense pathways,such as the oxidative burst,which involves the production of reactive oxygen species(ROS).The activities of antioxidant enzymes,including peroxidase(POD),superoxide dismutase(SOD),and catalase(CAT),were also upregulated,suggesting a role in mitigating oxidative damage caused by ROS.Our findings provide valuable insights into the molecular mechanisms underlying wheat resistance to Pst.By identifying key genes and pathways involved in this complex interaction,we can develop more effective strategies for breeding resistant wheat cultivars and managing this destructive disease.展开更多
BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prola...BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prolapse and hemorrhoids,and tissue selecting technique,are employed for treatment,they are often associated with postoperative complications,including unsatisfactory defecation,bleeding,and anal stenosis.In contrast,Xiaozhiling injection,a traditional Chinese medicine-based therapy,has emerged as a minimally invasive and effective alternative for internal hemorrhoids.This treatment offers distinct advantages,such as reduced dietary restrictions,broad applicability,and minimal induction of systemic inflammatory responses.Additionally,Xiaozhiling injection effectively eliminates hemorrhoid nuclei,prevents local tissue necrosis,preserves anal cushion integrity,and mitigates postoperative complications,including bleeding and prolapse.Despite its clinical efficacy,the molecular mechanisms underlying its therapeutic effects remain poorly understood,warranting further investigation.AIM To investigate the molecular mechanism underlying the therapeutic effect of Xiaozhiling injection in the treatment of internal hemorrhoids.METHODS An internal hemorrhoid model was established in rats,and the rats were randomly divided into a modeling group[control group(CK group)]and a treatment group.One week after injection,Stereo-seq and electron microscopy were used to study the changes in gene expression and subcellular structures in fibroblasts.RESULTS Single-cell sequencing revealed differences in the expression and transcript levels of the genes collagen 3 alpha 1,decorin,and actin alpha 2 in fibroblasts between the CK group and the treatment group.Spatial transcriptome analysis revealed that genes of the sphingosine kinase 1(Sphk1)/sphingosine-1-phosphate(S1P)pathway spatially overlapped with key genes of the transforming growth factor beta 1 pathway,namely,Sphk1,S1P receptor,and transforming growth factor beta 1,in the treatment group.The proportion of fibroblasts was lower in the treatment group than in the CK group,and Xiaozhiling treatment had a significant effect on the proportion of fibroblasts in hemorrhoidal tissue.Immunohistochemistry revealed a significant increase in the expression of a fibroblast marker.Electron microscopy showed that the endoplasmic reticulum of fibroblasts contained a large amount of glycogen,indicating cell activation.Fibroblast activation and the expression of key genes of the Sphk1-S1P pathway could be observed at the injection site,suggesting that after Xiaozhiling intervention,the Sphk1-S1P pathway could be activated to promote fibrosis.CONCLUSION Xiaozhiling injection exerts its therapeutic effects on internal hemorrhoids by promoting collagen synthesis and secretion in fibroblasts.After Xiaozhiling intervention,the Sphk1-S1P pathway can be activated to promote fibrosis.展开更多
Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.How...Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a“multi-omics”platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.展开更多
Spatial transcriptomics is an organizational study done on tissue sections that preserves the spatial information of the sample.Spatial transcriptomics aims to combine spatial information with gene expression data to ...Spatial transcriptomics is an organizational study done on tissue sections that preserves the spatial information of the sample.Spatial transcriptomics aims to combine spatial information with gene expression data to quantify the mRNA expression of a large number of genes in the spatial context of tissues and cells.As a paradigm shift in biological research,spatial transcriptomics can provide both spatial location information and transcriptome-level cellular gene expression data,elucidating the interactions between cells and the microenvironment.From the understanding of the entire functional life cycle of RNA to the characterization of molecular mechanisms to the mapping of gene expression in various tissue regions,by choosing the appropriate spatial transcriptome technology,researchers can achieve a deeper exploration of biological developmental processes,disease pathogenesis,etc.In recent years,the field of spatial transcriptomics has ushered in several challenges along with its rapid development,such as the dependence on sample types,the resolution of visualized genes,the difficulty of commercialization,and the ability to obtain detailed single-cell information.In this paper,we summarize and review the four major categories of spatial transcriptome technologies and compare and analyze the technical advantages and major challenges of multiple research strategies to assist current experimental design and research analysis.Finally,the importance of spatial transcriptomics in the integration of multi-omics analysis and disease modeling as well as the future development prospects are summarized and outlined.展开更多
Glucosinolates are important phytochemicals in Brassicaceae.We investigated the effect of CaCl_(2)-HCl electrolyzed water(CHEW)on glucosinolates biosynthesis in broccoli sprouts.The results showed that CHEW treatment ...Glucosinolates are important phytochemicals in Brassicaceae.We investigated the effect of CaCl_(2)-HCl electrolyzed water(CHEW)on glucosinolates biosynthesis in broccoli sprouts.The results showed that CHEW treatment significantly decreased reactive oxygen species(ROS)and malondialdeh yde(MDA)contents in broccoli sprouts.On the the 8^(th)day,compared to tap water treatment,the the total glucosinolate content of broccoli sprouts with CHEW treatment increased by 10.6%and calcium content was dramatically enhanced from 14.4 mg/g DW to 22.7 mg/g DW.Comparative transcriptome and metabolome analyses revealed that CHEW treatment activated ROS and calcium signaling transduction pathways in broccoli sprouts and they interacted through MAPK cascades.Besides,CHEW treatment not only promoted the biosynthesis of amino acids,but also enhanced the expression of structural genes in glucosinolate synthesis through transcription factors(MYBs,bHLHs,WRKYs,etc.).The results of this study provided new insights into the regulatory network of glucosinolates biosynthesis in broccoli sprouts under CHEW treatment.展开更多
Tumor research is a fundamental focus of medical science,yet the intrinsic heterogeneity and complexity of tumors present challenges in understanding their biological mechanisms of initiation,progression,and metastasi...Tumor research is a fundamental focus of medical science,yet the intrinsic heterogeneity and complexity of tumors present challenges in understanding their biological mechanisms of initiation,progression,and metastasis.Recent advancements in single-cell transcriptomic sequencing have revolutionized the way researchers explore tumor biology by providing unprecedented resolution.However,a key limitation of single-cell sequencing is the loss of spatial information during single-cell preparation.Spatial transcriptomics(ST)emerges as a cutting-edge technology in tumor research that preserves the spatial information of RNA transcripts,thereby facilitating a deeper understanding of the tumor heterogeneity,the intricate interplay between tumor cells and the tumor microenvironment.This review systematically introduces ST technologies and summarizes their latest applications in tumor research.Furthermore,we provide a thorough overview of the bioinformatics analysis workflow for ST data and offer an online tutorial(https://github.com/Siyua nHuan g1/ST_Analy sis_Handb ook).Lastly,we discuss the potential future directions of ST.We believe that ST will become a powerful tool in unraveling tumor biology and offer new insights for effective treatment and precision medicine in oncology.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 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.
基金supported by The National Key Research and Development Program of China(Grant no.2021YFA0910100)Healthy Zhejiang One Million People Cohort(Grant no.K-20230085)+5 种基金Post-doctoral Innovative Talent Support Program(Grant no.BX2023375)Lingyan Project of Zhejiang Provincial Department of Science and Technology(Grant no.2025C02059)the National Natural Science Foundation of China(Grant nos.82304946,82473489,and 82403546)Natural Science Foundation of Zhejiang Province(Grant nos.LR21H280001,LGF22H160056,ZCLQN25H1602,and LMS25H160006)Medicine and Health Science Fund of Zhejiang Province Health Commission(Grant nos.2025KY047 and 2022KY658)Traditional Chinese Medicine Science and Technology Project of Zhejiang Provincial Health Commission(Grant no.2022ZA023).
文摘Gastric cancer(GC)remains a major global health challenge,because of its poor prognosis and limited treatment options in advanced stages1,2.Recent advancements in immunotherapy,highlighted by the findings of the CHECKMATE-649,ORIENT-16,and KEYNOTE-859 trials,have markedly transformed the treatment paradigm for advanced gastric cancer(AGC)3-5.
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 Youth Foundation of China(Grant No.82102584).
文摘While bulk RNA sequencing and single-cell RNA sequencing have shed light on cellular heterogeneity and potential molecular mechanisms in the musculoskeletal system in both physiological and various pathological states,the spatial localization of cells and molecules and intercellular interactions within the tissue context require further elucidation.Spatial transcriptomics has revolutionized biological research by simultaneously capturing gene expression profiles and in situ spatial information of tissues,gradually finding applications in musculoskeletal research.This review provides a summary of recent advances in spatial transcriptomics and its application to the musculoskeletal system.The classification and characteristics of data acquisition techniques in spatial transcriptomics are briefly outlined,with an emphasis on widely-adopted representative technologies and the latest technological breakthroughs,accompanied by a concise workflow for incorporating spatial transcriptomics into musculoskeletal system research.The role of spatial transcriptomics in revealing physiological mechanisms of the musculoskeletal system,particularly during developmental processes,is thoroughly summarized.Furthermore,recent discoveries and achievements of this emerging omics tool in addressing inflammatory,traumatic,degenerative,and tumorous diseases of the musculoskeletal system are compiled.Finally,challenges and potential future directions for spatial transcriptomics,both as a field and in its applications in the musculoskeletal system,are discussed.
基金supported by the National Natural Science Foundation of China(Grant Nos.12090052,U24A2014,and 12325405).
文摘Spatial transcriptomics technology provides novel insights into the spatial organization of gene expression during embryonic development.In this study,we propose a method that integrates analysis across both temporal and spatial dimensions to investigate spatial transcriptomics data from mouse embryos at different developmental stages.We quantified the spatial expression pattern of each gene at various stages by calculating its Moran’s I.Furthermore,by employing time-series clustering to identify dynamic co-expression modules,we identified several developmentally stage-specific regulatory gene modules.A key finding was the presence of distinct,stage-specific gene network modules across different developmental periods:Early modules focused on morphogenesis,mid-stage on organ development,and late-stage on neural and tissue maturation.Functional enrichment analysis further confirmed the core biological functions of each module.The dynamic,spatially-resolved gene expression model constructed in this study not only provides new biological insights into the programmed spatiotemporal reorganization of gene regulatory networks during embryonic development but also presents an effective approach for analyzing complex spatiotemporal omics data.This work provides a new perspective for understanding developmental biology,regenerative medicine,and related fields.
基金supported by the National Natural Science Foundation of China(Nos.62303271,U1806202,62103397)the Natural Science Foundation of Shandong Province(ZR2023QF081)Funding for open access charge:the National Natural Science Foundation of China(Nos.62303271,U1806202).
文摘Recent advances in spatially resolved transcriptomics(SRT)have provided new opportunities for characterizing spatial structures of various tissues.Graph-based geometric deep learning has gained widespread adoption for spatial domain identification tasks.Currently,most methods define adjacency relation between cells or spots by their spatial distance in SRT data,which overlooks key biological interactions like gene expression similarities,and leads to inaccuracies in spatial domain identification.To tackle this challenge,we propose a novel method,SpaGRA(https://github.com/sunxue-yy/SpaGRA),for automatic multi-relationship construction based on graph augmentation.SpaGRA uses spatial distance as prior knowledge and dynamically adjusts edge weights with multi-head graph attention networks(GATs).This helps SpaGRA to uncover diverse node relationships and enhance message passing in geometric contrastive learning.Additionally,SpaGRA uses these multi-view relationships to construct negative samples,addressing sampling bias posed by random selection.Experimental results show that SpaGRA presents superior domain identification performance on multiple datasets generated from different protocols.Using SpaGRA,we analyze the functional regions in the mouse hypothalamus,identify key genes related to heart development in mouse embryos,and observe cancer-associated fibroblasts enveloping cancer cells in the latest Visium HD data.Overall,SpaGRA can effectively characterize spatial structures across diverse SRT datasets.
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 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 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The China Agriculture Research System Program(Project No.CARS-41-G04)Shenyang Governmental Science and Technology Program(Project No.22316-2-02)supported this work.
文摘Background Clostridium perfringens is a pathogen that secretes multiple toxins,impacting humans and animals.It can cause intestinal diseases such as necrotic enteritis.Although tannins inhibit C.perfringens proliferation,the precise underlying mechanisms are unclear.Objective This study integrated transcriptomics and metabolomics to systematically investigate the mechanism by which tannins,specifically pentagalloylglucose(PGG)and tannic acid(TA),inhibit C.perfringens and potential pathways to alleviate infection in vivo.Results Ion concentration measurements,flow cytometric analysis,and transmission electron microscopy revealed that PGG and TA damaged the cell membrane structure of C.perfringens,triggering cytoplasmic content leakage.Additionally,PGG and TA significantly affected C.perfringens at the transcriptional and metabolic levels.Bioinformatics analysis revealed that PGG and TA induced amino acid restriction,disrupted energy metabolism,and impeded the ability of C.perfringens to sense and respond to the external environment.In an in vitro C.perfringens-infected intestinal cell model,PGG and TA boundαtoxin,significantly reduced the mRNA expression of inflammatory factors,and improved intestinal barrier function and cell viability.Compared to PGG,TA exhibited stronger inhibitory activity against C.perfringens and binding toαtoxin.In vivo,PGG and TA alleviated C.perfringens-induced weight loss in mice,improved intestinal villi morphology,and reduced intestinal inflammation and tight junction gene dysregulation.Conclusion These findings indicate that tannins inhibit C.perfringens,improve gut tissue integrity and reduce inflammation,demonstrating their multi-target effects of resisting intestinal diseases caused by harmful bacteria.This offers new insights for plant polyphenol-based strategies against necrotic enteritis.
基金supported by the National Characteristic Vegetable Industry Technology System of China(Grant No.CARS24-A-07)the Jiangsu Modern Agricultural Industry Technology System Construction Special Fund(Grant No.JATS[2023]050)Xuzhou Academy of Agricultural Sciences Research Fund Project(Grant No.XM2021003)。
文摘Commercial cultivars of garlic,a popular condiment,are sterile,making genetic variation and germplasm innovation of this plant challenging.Understanding mechanism of gamete sterility in garlic and their key regulatory networks is therefore important for fertility restoration.In this work,we conducted a detailed phenotypic analysis of fertile and sterile garlic genotypes and found that enlargement of topset in the inflorescence of sterile genotypes led to abnormal flowers.Additional cytological observations showed that aberrant meiotic cytokinesis in sterile garlic ultimately resulted in pollen degeneration.Transcriptomics analysis of sterile and fertile genotypes identified possible molecular mechanisms underlying gamete abortion.A total of 100710 differentially expressed genes(DEGs)between the fertile and sterile garlic flowers at three stages of gamete development were identified,many of which were involved in homologous chromosome synapsis during meiosis,MYB transcription factor regulation,ribosome biogenesis and plant hormone signal transduction.Taken together,these results provide insight into the molecular mechanisms and regulatory networks underlying gamete development in garlic and point to a set of candidate genes for further functional characterization.
基金funded by the National Natural Science Foundation of China(32502517)the Open Project Program of State Key Laboratory of Crop Stress Biology for Arid Areas(SKLCSRHPKF20)+1 种基金Collaborative Innovation Project of Department of Education of Anhui Provincial(GXXT-2019-033)Horizontal project-Breeding of high yield and multi resistant wheat varieties(2021122401).
文摘Wheat stripe rust,a devastating disease caused by the fungal pathogen Puccinia striiformis f.sp.tritici(Pst),poses a significant threat to global wheat production.Growing resistant cultivars is a crucial strategy for wheat stripe rust management.However,the underlying molecular mechanisms of wheat resistance to Pst remain incompletely understood.To unravel these mechanisms,we employed high-throughput RNA sequencing(RNA-Seq)to analyze the transcriptome of the resistant wheat cultivar Mianmai 46(MM46)at different time points(24,48,and 96 h)post-inoculation with the Pst race CYR33.The analysis revealed that Pst infection significantly altered the expression of genes involved in photosynthesis and energy metabolism,suggesting a disruption of host cellular processes.Conversely,the expression of several resistance genes was upregulated,indicating activation of defense responses.Further analysis identified transcription factors(TFs),pathogen-related(PR)proteins,and chitinase-encoding genes as key players in wheat resistance to Pst.These genes likely contribute to the activation of defense pathways,such as the oxidative burst,which involves the production of reactive oxygen species(ROS).The activities of antioxidant enzymes,including peroxidase(POD),superoxide dismutase(SOD),and catalase(CAT),were also upregulated,suggesting a role in mitigating oxidative damage caused by ROS.Our findings provide valuable insights into the molecular mechanisms underlying wheat resistance to Pst.By identifying key genes and pathways involved in this complex interaction,we can develop more effective strategies for breeding resistant wheat cultivars and managing this destructive disease.
基金Supported by the National Natural Science Foundation of China,No.81774118the Foreign Cooperation Project of Science and Technology Department of Fujian Province,No.2023I0021the Medical Innovation Project of Fujian Province,No.2024CXB013.
文摘BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prolapse and hemorrhoids,and tissue selecting technique,are employed for treatment,they are often associated with postoperative complications,including unsatisfactory defecation,bleeding,and anal stenosis.In contrast,Xiaozhiling injection,a traditional Chinese medicine-based therapy,has emerged as a minimally invasive and effective alternative for internal hemorrhoids.This treatment offers distinct advantages,such as reduced dietary restrictions,broad applicability,and minimal induction of systemic inflammatory responses.Additionally,Xiaozhiling injection effectively eliminates hemorrhoid nuclei,prevents local tissue necrosis,preserves anal cushion integrity,and mitigates postoperative complications,including bleeding and prolapse.Despite its clinical efficacy,the molecular mechanisms underlying its therapeutic effects remain poorly understood,warranting further investigation.AIM To investigate the molecular mechanism underlying the therapeutic effect of Xiaozhiling injection in the treatment of internal hemorrhoids.METHODS An internal hemorrhoid model was established in rats,and the rats were randomly divided into a modeling group[control group(CK group)]and a treatment group.One week after injection,Stereo-seq and electron microscopy were used to study the changes in gene expression and subcellular structures in fibroblasts.RESULTS Single-cell sequencing revealed differences in the expression and transcript levels of the genes collagen 3 alpha 1,decorin,and actin alpha 2 in fibroblasts between the CK group and the treatment group.Spatial transcriptome analysis revealed that genes of the sphingosine kinase 1(Sphk1)/sphingosine-1-phosphate(S1P)pathway spatially overlapped with key genes of the transforming growth factor beta 1 pathway,namely,Sphk1,S1P receptor,and transforming growth factor beta 1,in the treatment group.The proportion of fibroblasts was lower in the treatment group than in the CK group,and Xiaozhiling treatment had a significant effect on the proportion of fibroblasts in hemorrhoidal tissue.Immunohistochemistry revealed a significant increase in the expression of a fibroblast marker.Electron microscopy showed that the endoplasmic reticulum of fibroblasts contained a large amount of glycogen,indicating cell activation.Fibroblast activation and the expression of key genes of the Sphk1-S1P pathway could be observed at the injection site,suggesting that after Xiaozhiling intervention,the Sphk1-S1P pathway could be activated to promote fibrosis.CONCLUSION Xiaozhiling injection exerts its therapeutic effects on internal hemorrhoids by promoting collagen synthesis and secretion in fibroblasts.After Xiaozhiling intervention,the Sphk1-S1P pathway can be activated to promote fibrosis.
基金supported by the National Natural Science Foundation of China(Grant No.:82273888)Natural Science Foundation of Shandong Province(Grant Nos.ZR2022QH257,ZR2020YQ60)+2 种基金Shandong Major Technological Innovation Project(Project No.:2021CXGC010508)Taishan Scholars Program of Shandong Province(Program Nos.:tsqn202103096,tsqn202211204)Shandong Province Science and Technology Small and Medium Enterprises Innovation Ability Enhancement Project(Project No.:2022TSGC2210).
文摘Eclipta prostrata L.has been used in traditional medicine and known for its liver-protective properties for centuries.Wedelolactone(WEL)and demethylwedelolactone(DWEL)are the major coumarins found in E.prostrata L.However,the comprehensive characterization of these two compounds on non-alcoholic fatty liver disease(NAFLD)still remains to be explored.Utilizing a well-established zebrafish model of thioacetamide(TAA)-induced liver injury,the present study sought to investigate the impacts and mechanisms of WEL and DWEL on NAFLD through integrative spatial metabolomics with liver-specific transcriptomics analysis.Our results showed that WEL and DWEL significantly improved liver function and reduced the accumulation of fat in the liver.The biodistributions and metabolism of these two compounds in whole-body zebrafish were successfully mapped,and the discriminatory endogenous metabolites reversely regulated by WEL and DWEL treatments were also characterized.Based on spatial metabolomics and transcriptomics,we identified that steroid biosynthesis and fatty acid metabolism are mainly involved in the hepatoprotective effects of WEL instead of DWEL.Our study unveils the distinct mechanism of WEL and DWEL in ameliorating NAFLD,and presents a“multi-omics”platform of spatial metabolomics and liver-specific transcriptomics to develop highly effective compounds for further improved therapy.
基金supported by the National Natural Science Foundation of China(Grant No.22275071)
文摘Spatial transcriptomics is an organizational study done on tissue sections that preserves the spatial information of the sample.Spatial transcriptomics aims to combine spatial information with gene expression data to quantify the mRNA expression of a large number of genes in the spatial context of tissues and cells.As a paradigm shift in biological research,spatial transcriptomics can provide both spatial location information and transcriptome-level cellular gene expression data,elucidating the interactions between cells and the microenvironment.From the understanding of the entire functional life cycle of RNA to the characterization of molecular mechanisms to the mapping of gene expression in various tissue regions,by choosing the appropriate spatial transcriptome technology,researchers can achieve a deeper exploration of biological developmental processes,disease pathogenesis,etc.In recent years,the field of spatial transcriptomics has ushered in several challenges along with its rapid development,such as the dependence on sample types,the resolution of visualized genes,the difficulty of commercialization,and the ability to obtain detailed single-cell information.In this paper,we summarize and review the four major categories of spatial transcriptome technologies and compare and analyze the technical advantages and major challenges of multiple research strategies to assist current experimental design and research analysis.Finally,the importance of spatial transcriptomics in the integration of multi-omics analysis and disease modeling as well as the future development prospects are summarized and outlined.
基金supported by the National Natural Science Foundation of China(31972091)。
文摘Glucosinolates are important phytochemicals in Brassicaceae.We investigated the effect of CaCl_(2)-HCl electrolyzed water(CHEW)on glucosinolates biosynthesis in broccoli sprouts.The results showed that CHEW treatment significantly decreased reactive oxygen species(ROS)and malondialdeh yde(MDA)contents in broccoli sprouts.On the the 8^(th)day,compared to tap water treatment,the the total glucosinolate content of broccoli sprouts with CHEW treatment increased by 10.6%and calcium content was dramatically enhanced from 14.4 mg/g DW to 22.7 mg/g DW.Comparative transcriptome and metabolome analyses revealed that CHEW treatment activated ROS and calcium signaling transduction pathways in broccoli sprouts and they interacted through MAPK cascades.Besides,CHEW treatment not only promoted the biosynthesis of amino acids,but also enhanced the expression of structural genes in glucosinolate synthesis through transcription factors(MYBs,bHLHs,WRKYs,etc.).The results of this study provided new insights into the regulatory network of glucosinolates biosynthesis in broccoli sprouts under CHEW treatment.
基金supported by the National Key R&D Program of China[2020YFE0204200 to R.X.]the National Natural Science Foundation of China[12371286,11971039 to R.X.,12201219 to J.M.]+1 种基金Sino-Russian Mathematics Center,Foundation of Qinglonghu laboratory,Shanghai Sailing Program(No.21YF1410600 to J.M.)Shanghai Key Program of Computational Biology(No.23JS1400500,23JS1400800 to J.M.).
文摘Tumor research is a fundamental focus of medical science,yet the intrinsic heterogeneity and complexity of tumors present challenges in understanding their biological mechanisms of initiation,progression,and metastasis.Recent advancements in single-cell transcriptomic sequencing have revolutionized the way researchers explore tumor biology by providing unprecedented resolution.However,a key limitation of single-cell sequencing is the loss of spatial information during single-cell preparation.Spatial transcriptomics(ST)emerges as a cutting-edge technology in tumor research that preserves the spatial information of RNA transcripts,thereby facilitating a deeper understanding of the tumor heterogeneity,the intricate interplay between tumor cells and the tumor microenvironment.This review systematically introduces ST technologies and summarizes their latest applications in tumor research.Furthermore,we provide a thorough overview of the bioinformatics analysis workflow for ST data and offer an online tutorial(https://github.com/Siyua nHuan g1/ST_Analy sis_Handb ook).Lastly,we discuss the potential future directions of ST.We believe that ST will become a powerful tool in unraveling tumor biology and offer new insights for effective treatment and precision medicine in oncology.
