Bone and skeletal muscle are essential components of musculoskeletal system,enabling movement,load-bearing,and systemic homeostasis.These tissues communicate through dynamic bone-muscle crosstalk mediated by cytokines...Bone and skeletal muscle are essential components of musculoskeletal system,enabling movement,load-bearing,and systemic homeostasis.These tissues communicate through dynamic bone-muscle crosstalk mediated by cytokines,growth factors,and extracellular-matrix(ECM)proteins.The spatial organization of these mediators is critical for maintaining tissue integrity,and its disruption contributes to diseases,such as osteoporosis,sarcopenia,and metabolic syndrome.Despite this importance,spatial transcriptomics(ST)studies of bone-muscle interactions remain limited.Here,we applied 10x Genomics Visium ST with computational tools,e.g.,SMART and CellChat,to deconvolute cell-type composition and characterize cell-cell communication networks and ligand-receptor(L-R)interactions in mouse femur and adjacent skeletal muscle.We identified eight major cell types(erythroid cells,endothelial cells,skeletal muscle cells,osteoblasts,myeloid cells,monocytes/macrophages,mesenchymal stem cells,and adipocytes)with distinct spatial transcriptional profiles and thirteen CellChat-inferred pathways,such as ECM-receptor related(e.g.,COLLAGEN,TENASCIN,THBS)and secreted-signaling involved(e.g.,VEGF)pathways.Representative L-R pairs include Col1a1/Col1a2-Sdc4,mediating osteoblast-to-muscle interactions,and Col4a1-Sdc4,facilitating muscle-to-osteoblast interactions in COLLAGEN,Tnxb-Sdc4 in TENASCIN,supporting muscle-to-osteoblast/muscle/myeloid/endothelial communication,Comp-Sdc4 in THBS,driving monocyte/macrophage-to-osteoblast/muscle signaling,and Vegfa-Vegfr1/Vegfr2 in VEGF,mediating muscle-toendothelial/myeloid signaling.Immunostaining validated colocalization of several representative L-R pairs with their corresponding cells.Additionally,independent mouse and human bone scRNA-seq datasets reproduced most of the pathways and L-R pairs identified in ST,underscoring the robustness and cross-species relevance of our findings.Together,we present an initial spatially resolved transcriptome-wide map of bone-muscle intercellular communication,providing novel insights into molecular crosstalk and establishing groundwork for future studies in musculoskeletal disorders.展开更多
Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on ...Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on repairing skeletal muscle injuries has been rarely reported.In this study,a mouse model of muscle injury was constructed and found that OVA significantly increased muscle weight,muscle thickness,and exercise capacity in muscle-injured mice.Meanwhile,OVA improved the morphology of muscle tissues by reducing serum levels of urea nitrogen,creatine kinase,and lactate dehydrogenase,as well as decreasing the levels of inflammatory factors interleukin(IL)-1β,tumor necrosis factor α,and IL-6,respectively.In addition,transcriptomic and metabolomic analyses revealed that OVA could enhance muscle tissue morphology by upregulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and improving amino acid metabolism through the upregulation of Col11a2,Ccn2,Thbs1,Tnc,Klf2,Bcl2l1,Adh3a1,and Rsad1.The study provided a theoretical foundation for understanding the molecular mechanisms in OVA-aided muscle injury repair.展开更多
Rheumatoid arthritis(RA)is a common long-term autoimmune disease that causes synovial tissue to grow and behave like a tumor when inflammatory factors are present.This can cause joint pain,muscle loss,and other seriou...Rheumatoid arthritis(RA)is a common long-term autoimmune disease that causes synovial tissue to grow and behave like a tumor when inflammatory factors are present.This can cause joint pain,muscle loss,and other serious problems.Therefore,finding natural anti-RA products and effective treatment strategies is crucial for achieving good prognoses in RA patients.The deer bone is rich in protein,which has the effect of eliminating rheumatism and strengthening muscles and bones.Through multiple gel chromatography purifications,we obtained the deer bone protein(DBP)with a protein content of 76.43%,which was then analyzed using label-free proteomics.Subsequently,an adjuvant arthritis(AA)rat model was established.The ferroptosis pathway was chosen for study based on transcriptomic analysis of AA rat synovial tissue.The molecules with the best docking scores,Nrf2 and Keapl,were then visualized to confirm their validity.Additionally,results from electron microscopy observations,and Western blot(WB)experiments indicated that deer bone protein activates the ferroptosis signaling pathway,alleviating synovial hyperplasia.Therefore,regulating the Keapl/Nrf2 signaling pathway is key to promoting ferroptosis of deer bone protein to improve RA.This study provides new insights into the search for natural foods to improve RA and offers theoretical support for the full development and utilization of Sika deer resources and deer bone products.展开更多
Tomato(Solanum lycopersicum L.)is an herbaceous annual belonging to the genus Solanum in the family Solanaceae,native to South America.Protected cultivation has significantly increased annual tomato yields(Zhang et al...Tomato(Solanum lycopersicum L.)is an herbaceous annual belonging to the genus Solanum in the family Solanaceae,native to South America.Protected cultivation has significantly increased annual tomato yields(Zhang et al.,2024;Lou et al.,2025).Balancing quality and yield improvement has therefore become essential to meeting market needs(Gao et al.,2023).Numerous studies on protected tomato production highlight theeffectiveness of mulch cultivation(Dhaliwal et al.,2016).展开更多
Biological systems exhibit high complexity and heterogeneity:the maintenance of physiological homeostasis and the progression of disease in the human body are fundamentally driven by the discrete states,behaviors,and ...Biological systems exhibit high complexity and heterogeneity:the maintenance of physiological homeostasis and the progression of disease in the human body are fundamentally driven by the discrete states,behaviors,and interactions of billions of individual cells[1].展开更多
Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,t...Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.展开更多
This article presents a Hierarchical Pathway-Masked Attention Autoencoder(H-PAAE),a biologically inspired representation-learning framework that enables explainable AI-guided cancer diagnosis.The model directly integr...This article presents a Hierarchical Pathway-Masked Attention Autoencoder(H-PAAE),a biologically inspired representation-learning framework that enables explainable AI-guided cancer diagnosis.The model directly integrates the curated MSigDB Hallmark pathways,introducing pathway-constrained information flow and mechanistic interpretability through multi-level attention mechanisms.Based on TCGA RNA-seq data from 33 tumor types,H-PAAE compresses approximately 20,000 genes into a 128-dimensional latent space while preserving biologically meaningful structure.When used with XGBoost classification,H-PAAE delivers 92.37%test accuracy and 99.38%macro-AUROC with robust cross-validation results(92.5±0.6%).SHAP analysis identifies a small number of key latent features,corresponding to conserved oncogenic processes,and pathway enrichment analysis shows strong overlap with cancer hallmarks.H-PAAE provides a clear and interpretable biological foundation for pan-cancer classification,with well-calibrated posterior probabilities that can be used for clinical decision-making,and can be easily integrated into multimodal diagnostic workflows.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
Gouty arthritis(GA) is an inflammatory disorder characterized by the deposition of monosodium urate(MSU) crystals in joint tissues. Pulchinenoside B4(B4) has broad-spectrum antiinflammatory properties,but its role and...Gouty arthritis(GA) is an inflammatory disorder characterized by the deposition of monosodium urate(MSU) crystals in joint tissues. Pulchinenoside B4(B4) has broad-spectrum antiinflammatory properties,but its role and potential mechanism in the pathogenesis of GA are still unclear. The purpose of this study is to comprehensively elucidate the therapeutic effect and mechanism of B4 on GA by integrating transcriptome analysis and in vitro and in vivo experiments. In the MSU-induced mouse GA model,B4 treatment significantly improved ankle edema and reduced inflammatory cell infiltration. Through the analysis of transcriptome sequencing results,we identified multiple differentially expressed long non-coding RNAs(lncRNAs),such as Nod1,Rbck1 and Pycard. In the in-depth exploration of the mechanism,we focused on the NOD-like receptor signaling pathway,NF-κB signaling cascade,and B4-regulated macrophage polarization. In vitro and in vivo models,we confirmed that B4 significantly inhibited the expression and activation of key components of NLRP3 inflammasome(such as ASC,Caspase-1 and IL-1β) by qPCR,Western blot and immunofluorescence. Flow cytometry and immunofluorescence analysis further showed that B4 could prevent MSU-induced macrophage polarization to pro-inflammatory M1 phenotype.Based on these results,this study elucidated the mechanism of B4 improving MSU-induced GA inflammatory response by inhibiting NLRP3 inflammasome activation and blocking M1 macrophage polarization. These results suggest that B4 has great potential as a candidate drug for the treatment of GA.展开更多
Background:Cervicitis is a common gynecological disease,which triggers local inflammation and tissue damage by a complex mechanism,seriously affecting women’s health.Chinese medicine plays a prominent role in the tre...Background:Cervicitis is a common gynecological disease,which triggers local inflammation and tissue damage by a complex mechanism,seriously affecting women’s health.Chinese medicine plays a prominent role in the treatment of gynecological inflammation.Shuangshi Tongling Capsule(SSTL),as a traditional Chinese medicine(TCM)compound,needs to be further elucidated for the treatment of cervicitis.Methods:Cervicitis was induced with 25%phenol gel(except controls),followed by 12-day intragastric treatment.Outcomes included genital inflammation scores,uterine index,and histopathology(HE staining).Serum tumor necrosis factor-α(TNF-α),Interleukin(IL)-6,IL-8,and IL-1βwere measured via ELISA.Integrated metabolomics-transcriptomics and Western blotting identified mechanistic pathways.Results:SSTL alleviated cervicitis in rats by improving uterine histopathology,reducing external genital inflammation scores(P<0.01 vs.model),and reversing uterine hypertrophy(P<0.05).Serum pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-8)were suppressed(P<0.01),with concurrent weight restoration.Multi-omics analysis identified AMPK signaling as pivotal,validated by downregulation of p-NF-κB(P<0.05)and upregulation of p-AMPK/SIRT1(P<0.05)in uterine tissues,indicating SSTL mitigates inflammation through AMPK/NF-κB/SIRT1 modulation.Conclusion:This study found that SSTL ameliorates cervicitis in rats through the expression of AMPK pathway-related proteins.展开更多
Male infertility affects approximately 17.5%of the global reproductive-age population,with disruption of the testicular spermatogenic microenvironment-particularly the spermatogonial stem cell niche-representing a cen...Male infertility affects approximately 17.5%of the global reproductive-age population,with disruption of the testicular spermatogenic microenvironment-particularly the spermatogonial stem cell niche-representing a central pathogenic mechanism.Single-cell RNA sequencing has enabled unprecedented resolution of cellular heterogeneity within the human testis;however,its translational value remains constrained by population data imbalance and limited integration across molecular layers.Here,we synthesize single-cell RNA sequencing studies published between January 2018 and September 2025 to construct a microenvironment-centered mechanistic framework linking inflammaging,NLRP3 inflammasome activation,and progressive spermatogonial stem cell depletion in nonobstructive azoospermia,supported by convergent single-cell,bulk transcriptomic,and emerging preclinical evidence.We further discuss transgenerational epigenetic effects mediated by sperm small non-coding RNAs and critically evaluate translational barriers,including ancestry bias,technical limitations of singlecell platforms,and ethical challenges of germline intervention.We propose that future clinical translation will require multiethnic cohort construction and artificial intelligence-driven multi-omics integration to enable stem cell-oriented precision diagnosis and therapy for male infertility.展开更多
Spatial transcriptomics(ST)is a powerful assay for capturing gene expression in tissues.However,due to inherent limitations of spatial resolution,most existing ST datasets remain at a multicellular resolution,which hi...Spatial transcriptomics(ST)is a powerful assay for capturing gene expression in tissues.However,due to inherent limitations of spatial resolution,most existing ST datasets remain at a multicellular resolution,which hinders a comprehensive understanding of spatial organization.We propose SpatioCell,a computational algorithm to automatically extract both cell type and expression information at single-cell resolution from ST data,through a morpho-transcriptomic spatial reconstruction framework solved via dynamic programming,integrating morphological and transcriptomic information.This framework enables deterministic single-cell spatial reconstruction,assigning cell identities to precise locations rather than inferring the spot-level cell type composition and expression.It further uncovers overlooked microenvironmental features while correcting deconvolution errors.Using ST data from triple-negative breast cancer as an example,SpatioCell reveals the significance of the distance between cancer-associated fibroblasts(CAFs)and tumor or immune cells in terms of disease progression.Thus,the establishment of SpatioCell will broaden the biomedical applications of ST and facilitate investigations of single-cell spatial organization.展开更多
BACKGROUND Chronic hepatitis B(CHB)is a significant global health issue,and interferon(IFN)is one of the main first-line therapies for CHB.AIM To investigate the altered transcriptome,metabolites,and their correlation...BACKGROUND Chronic hepatitis B(CHB)is a significant global health issue,and interferon(IFN)is one of the main first-line therapies for CHB.AIM To investigate the altered transcriptome,metabolites,and their correlations,as well as the effects and mechanisms of IFN treatment for CHB.METHODS The patients received peginterferon alfa-2b at a dose of 180μg for 0,1,3,and 6 months and serum samples were collected for clinical biological assays,transcriptomics,and metabolomics analyses.RESULTS The results showed that IFN-related immune pathways and neutrophil extracellular traps(NETs)were the most significantly altered pathways following IFN treatment.Correlation analysis revealed a strong link between immune system-related genes in the transcriptome and dipeptides in the metabolome during IFN-αtreatment.Notably,core components of NETs,including histones H2A clustered histone 14,H2B clustered histone 5,H3 clustered histone 1,and H4 clustered histone 4,were significantly increased after IFN treatment.The positively charged histones may bind to the negatively charged viral envelope,potentially enhancing the antiviral effect.CONCLUSION Integrated non-targeted transcriptomic and metabolomic analyses to CHB patients undergoing IFN-αtreatment revealed that IFN-related immune pathways and NETs were the most significantly affected pathways during IFN treatment.These findings provide a deeper understanding of the role of NETs and dipeptides in the antiviral response to IFN treatment for CHB.展开更多
Dynamic transitions of mature osteoblasts between active and quiescent states are essential for bone homeostasis and present a promising target for osteoanabolic therapy.However,these transitions remain poorly underst...Dynamic transitions of mature osteoblasts between active and quiescent states are essential for bone homeostasis and present a promising target for osteoanabolic therapy.However,these transitions remain poorly understood due to cellular heterogeneity and limited spatial context.Here,we employed spatially resolved osteoblast-traced transcriptomics,integrating an osteoblast-specific lineage tracing study and spatially resolved laser-activated cell sorting(SLACS),to profile osteoblast states on quiescent bone surfaces.This approach identified transforming growth factor-beta(TGF-β)signaling as a regulator of osteoblast activation.We further validated this role using single-cell RNA sequencing,in vitro functional assays,and in vivo.In a hindlimb unloading mouse model,dual inhibition of TGF-βand sclerostin enhanced bone mass and mitigated bone loss more effectively than sclerostin inhibition alone.These findings reveal a mechanistic role for TGF-βin regulating osteoblast dynamics and propose a dual-target therapeutic strategy that enhances the efficacy of anti-sclerostin treatment in osteoporosis.展开更多
OBJECTIVE To investigate the therapeutic effects of Xianlian Jiedu Decoction(XLJDD)on colitis-associated colorectal cancer(CAC)and to explore its potential underlying mechanisms.METHODS An azoxymethane/dextran sulfate...OBJECTIVE To investigate the therapeutic effects of Xianlian Jiedu Decoction(XLJDD)on colitis-associated colorectal cancer(CAC)and to explore its potential underlying mechanisms.METHODS An azoxymethane/dextran sulfate sodium(AOM/DSS)-induced CAC mouse model was established.UPLC-Q-TOF/MS was employed to identify prototype compounds present in colonic tissue after XLJDD administration.Network pharmacology analysis,molecular docking,transcriptomic sequencing,and valida‑tion of key pathway-related genes were further conducted to systematically elucidate the intervention effects and potential mechanisms of XLJDD against CAC.RESULTS In the AOM/DSS-induced CAC mouse model,XLJDD treatment markedly improved tumor-associated pathological features,as evidenced by reduced tumor burden,restored colon length,and alleviated disease activity index(DAI).UPLC-Q-TOF/MS analysis identified 22 exogenous compounds derived from XLJDD in colonic tissue.In addition,XLJDD sig‑nificantly downregulated the expression of multiple inflammatory cytokines while upregulating tight junction-related genes in the co‑lon.Transcriptomic analysis revealed that XLJDD treatment enhanced overall PPAR signaling pathway activity while suppressing the Wnt signaling pathway.Consistently,the expression levels of PPAR pathway-related genes Pparα,Cpt1a,and Ehhadh were upregulated following XLJDD intervention(P<0.05,P<0.01),whereas the Wnt pathway-related genes Axin2 and Lef1 were significantly downregulated(P<0.05,P<0.01).CONCLUSION XLJDD may intervene in inflammation-associated colorectal carcinogenesis by activating the PPAR signaling pathway and suppressing the Wnt signaling pathway.展开更多
Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underl...Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underlying the high anthocyanin accumulation during the fruit development and colouration of rabbiteye blueberry fruit,have not yet been fully clarified so far.The fruit anthocyanin content of rabbiteye blueberry in the karstic area of Guizhou Province,China,is much higher compared to that in other regions,and the fruit colour is highly affected by anthocyanin accumulation.Currently,the untargeted metabolomics and HPLC assays have been carried out using rabbiteye blueberry fruit at various stages,and it was investigated that cyanidin(Cy)and pelargonidin(Pg)reached their peaks at the red fruit(RF)stage,whereas delphinidin(Dp),petudinin(Pt),malvidin(Mv),and peonidin(Pn)got their ceilings at the mature fruit(MF)stage.Transcriptome and co-expression network analyses showed that 27 differentially expressed genes(DEGs)were associated with anthocyanin content,among which VdMYB56,belonging to the R2R3-MYB family,was markedly up-regulated during the development and colouration of fruit,and was significantly higher in the skin than in the pulp.Furthermore,VdMYB56-overexpressing tomato fruits demonstrated a substantial elevation in anthocyanin content on the 35th day after flowering(DAF).It was worth noting that VdMYB56 could directly bind to the promoter of Vd3GT to enhance its expression,thereby further strengthening the anthocyanin accumulation.Meantime,multiple assays verified that VdMYB69,an R2R3-MYB member,might interact with VdMYB56,leading to the promotion of VdMYB56 expression.Conclusively,the VdMYB56-VdMYB69 module is a positive regulator of anthocyanin biosynthesis in rabbiteye blueberry,which may provide new insights into high-anthocyanin breeding,particularly for the southern karstic regions.展开更多
Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is...Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.展开更多
Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dyna...Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dynamic transcription of bovine germ cell population.Results In this study,we used Stereo-seq to construct a spatial transcription map of bovine testicular tissue at two ages.Four germ cell groups and five somatic cell groups were determined,and functional enrichment characterized their different biological functions and the differences between calves and adult bulls.At the same time,we also defined the subpopulations of cells and marker genes,then,clarified the communications between germ cells.Conclusion Our study constructed a spatial transcription map of bovine testicular tissue for the first time,and systematically described the dynamic transcription changes during spermatogenesis.These data laid the foundation for the study of spermatogenesis in large mammals and elucidated the transcriptional dynamics underlying male germ cell development.展开更多
Root tips,which represent the initial stage of taproot development,serve as an ideal model for investigating plant growth and secondary metabolism.However,studies of root tips in Panax species have been limited,restri...Root tips,which represent the initial stage of taproot development,serve as an ideal model for investigating plant growth and secondary metabolism.However,studies of root tips in Panax species have been limited,restricting our understanding of cell fate transitions during early root development and the cellular heterogeneity associated with ginsenosides biosynthesis.To address this gap,we conducted single-cell RNA sequencing(scRNA-seq)and spatial metabolomics analyses on the root tips of three Panax species:Panax notoginseng,Panax ginseng,and Panax quinquefolium.Our research reconstructed the developmental trajectory of the early endodermis and revealed epidermis-specific expression patterns of key enzyme genes involved in ginsenosides biosynthesis.We identified several novel transcription factors(TFs):IAA29(which positively regulates endodermis suberization)and MYB2/MYB78(positive regulators of ginsenosides biosynthesis),validated by dual-LUC reporter and electrophoretic mobility shift assay(EMSA).Conserved and divergent ligand-receptor interaction patterns across the three Panax species were discovered,with the FAD gene family exhibiting tissue-and species-specific expression.Cell-specific genes expression was confirmed by RNA in situ hybridization.Mass spectrometry imaging(MSI)mapped ginsenosides spatial distribution,while LC–MS/MS verified species-specific biosynthesis.This study presents a singlecell transcriptional landscape of early differentiation and cell type-specific ginsenosides accumulation in the Panax genus.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-CO2 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
基金supported or benefited by grants from the National Institutes of Health[U19AG055373,P20GM109036,R01AR069055,and R01AG061917].
摘要Bone and skeletal muscle are essential components of musculoskeletal system,enabling movement,load-bearing,and systemic homeostasis.These tissues communicate through dynamic bone-muscle crosstalk mediated by cytokines,growth factors,and extracellular-matrix(ECM)proteins.The spatial organization of these mediators is critical for maintaining tissue integrity,and its disruption contributes to diseases,such as osteoporosis,sarcopenia,and metabolic syndrome.Despite this importance,spatial transcriptomics(ST)studies of bone-muscle interactions remain limited.Here,we applied 10x Genomics Visium ST with computational tools,e.g.,SMART and CellChat,to deconvolute cell-type composition and characterize cell-cell communication networks and ligand-receptor(L-R)interactions in mouse femur and adjacent skeletal muscle.We identified eight major cell types(erythroid cells,endothelial cells,skeletal muscle cells,osteoblasts,myeloid cells,monocytes/macrophages,mesenchymal stem cells,and adipocytes)with distinct spatial transcriptional profiles and thirteen CellChat-inferred pathways,such as ECM-receptor related(e.g.,COLLAGEN,TENASCIN,THBS)and secreted-signaling involved(e.g.,VEGF)pathways.Representative L-R pairs include Col1a1/Col1a2-Sdc4,mediating osteoblast-to-muscle interactions,and Col4a1-Sdc4,facilitating muscle-to-osteoblast interactions in COLLAGEN,Tnxb-Sdc4 in TENASCIN,supporting muscle-to-osteoblast/muscle/myeloid/endothelial communication,Comp-Sdc4 in THBS,driving monocyte/macrophage-to-osteoblast/muscle signaling,and Vegfa-Vegfr1/Vegfr2 in VEGF,mediating muscle-toendothelial/myeloid signaling.Immunostaining validated colocalization of several representative L-R pairs with their corresponding cells.Additionally,independent mouse and human bone scRNA-seq datasets reproduced most of the pathways and L-R pairs identified in ST,underscoring the robustness and cross-species relevance of our findings.Together,we present an initial spatially resolved transcriptome-wide map of bone-muscle intercellular communication,providing novel insights into molecular crosstalk and establishing groundwork for future studies in musculoskeletal disorders.
基金funded by the Project of National Key Research and Development Program of China(2022YFD2101001)the Project of National Natural Science Foundation of China(32172226)+4 种基金China Agriculture Research System(CARS-40-K25CARS-40-S11)the Special Fund for Anhui Agriculture Research System(AHCYJSTX-NCPJG)-15the Project of Key Laboratory for Animal Food Green Manufacturing and Resource Ming of Anhui Province(PA2023GDSK0125)the Cooperative Project of Hefei University of Technology-Anhui Rongda Food Co.,Ltd.(W2020JSKF0489).
摘要Skeletal muscle injuries are prone to induce fatigue,decrease resistance and imbalances in the body.Although ovalbumin(OVA)has such biological effect as promoting tissue development and immunomodulation,its impact on repairing skeletal muscle injuries has been rarely reported.In this study,a mouse model of muscle injury was constructed and found that OVA significantly increased muscle weight,muscle thickness,and exercise capacity in muscle-injured mice.Meanwhile,OVA improved the morphology of muscle tissues by reducing serum levels of urea nitrogen,creatine kinase,and lactate dehydrogenase,as well as decreasing the levels of inflammatory factors interleukin(IL)-1β,tumor necrosis factor α,and IL-6,respectively.In addition,transcriptomic and metabolomic analyses revealed that OVA could enhance muscle tissue morphology by upregulating the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and improving amino acid metabolism through the upregulation of Col11a2,Ccn2,Thbs1,Tnc,Klf2,Bcl2l1,Adh3a1,and Rsad1.The study provided a theoretical foundation for understanding the molecular mechanisms in OVA-aided muscle injury repair.
基金supported by funding from the Major Science and Technology Projects in Jilin Province(20220304001YY,20220304003YY).
摘要Rheumatoid arthritis(RA)is a common long-term autoimmune disease that causes synovial tissue to grow and behave like a tumor when inflammatory factors are present.This can cause joint pain,muscle loss,and other serious problems.Therefore,finding natural anti-RA products and effective treatment strategies is crucial for achieving good prognoses in RA patients.The deer bone is rich in protein,which has the effect of eliminating rheumatism and strengthening muscles and bones.Through multiple gel chromatography purifications,we obtained the deer bone protein(DBP)with a protein content of 76.43%,which was then analyzed using label-free proteomics.Subsequently,an adjuvant arthritis(AA)rat model was established.The ferroptosis pathway was chosen for study based on transcriptomic analysis of AA rat synovial tissue.The molecules with the best docking scores,Nrf2 and Keapl,were then visualized to confirm their validity.Additionally,results from electron microscopy observations,and Western blot(WB)experiments indicated that deer bone protein activates the ferroptosis signaling pathway,alleviating synovial hyperplasia.Therefore,regulating the Keapl/Nrf2 signaling pathway is key to promoting ferroptosis of deer bone protein to improve RA.This study provides new insights into the search for natural foods to improve RA and offers theoretical support for the full development and utilization of Sika deer resources and deer bone products.
基金supported by the earmarked fund for National Natural Science Foundation of China(Grant No.32372793)Beijing Rural Revitalization Agricultural Science and Technology Project(Grant No.NY2502120425)+4 种基金The Ningxia Hui Autonomous Region key Research and Development Program project(Grant No.2023BCF01046)Earmarked Fund for Modern Agro-industry Technology Research System(Grant Nos.CARS-24-B04CARS-23-B05)The Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(Grant No.CAASASTIP-IVFCAAS)provided by the Key Laboratory of Biology and Genetic Improvement of Horticultural Crops(Vegetables),Ministry of Agriculture and Rural Affairs,China。
摘要Tomato(Solanum lycopersicum L.)is an herbaceous annual belonging to the genus Solanum in the family Solanaceae,native to South America.Protected cultivation has significantly increased annual tomato yields(Zhang et al.,2024;Lou et al.,2025).Balancing quality and yield improvement has therefore become essential to meeting market needs(Gao et al.,2023).Numerous studies on protected tomato production highlight theeffectiveness of mulch cultivation(Dhaliwal et al.,2016).
摘要Biological systems exhibit high complexity and heterogeneity:the maintenance of physiological homeostasis and the progression of disease in the human body are fundamentally driven by the discrete states,behaviors,and interactions of billions of individual cells[1].
基金the National Natural Science Foundation of China(82204935)the construction project of Zhao Feng National Old Pharmacist Inheritance Studio of State Administration of Traditional Chinese Medicine(National Traditional Chinese Medicine Education Letter[2024]255)+1 种基金the open project of the Key Laboratory of Basic and New Drug Research of Traditional Chinese Medicine in Shaanxi Province(KF202302)the project of Xi’an Municipal Bureau of Science and Technology(23YXYJ0042)for financial support.
摘要Background:One of the first hundred traditional Chinese medicines(TCM)formulas administered in China,Qianghuo Shengshi Decoction(QSD)has a positive clinical and therapeutic impact on rheumatoid arthritis(RA).Even so,there is still not enough knowledge on the active ingredients and possible ways that QSDs might work to treat RA.This study systematically investigated the active ingredients and mechanisms of action of QSD for treating wind-cold-dampness arthralgia type RA.Methods:UHPLC-QE-MS and network pharmacology techniques were employed to predict the potential active constituents,targets,and associated signalling pathways.Then,the therapeutic effect of QSD was examined using a wind-cold-dampness arthralgia paralytic RA rat model.Finally,the complex mechanism was comprehensively elucidated by integrating transcriptomics and network pharmacology.The above mechanisms were also verified by molecular docking,immunohistochemistry and Western blot.Results:UHPLC-QE-MS and network pharmacology analysis revealed that ferulic acid,imperatorin,magnolol,quercetin,and scopoletin could be the primary constituents in QSD responsible for its anti-RA effects.Animal experiments showed that QSD can significantly inhibit rat joint swelling degree,decrease the content of serum rheumatoid factor(RF),interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,and anti-citrullinated protein antibodies(ACPA),and increase the content of IL-4,IL-10 to relieve the clinical symptoms of wind-cold-dampness arthralgia type RA.The mechanistic study showed that QSD may effectively inhibit rat synovial hyperplasia via promoting autophagy and apoptosis of synovial cells by regulating the PI3K/Akt/mTOR signalling pathway.Conclusion:This study identifies key active ingredients in QSD and elucidates its potential mechanism for treating wind-cold-dampness arthralgia type RA,providing a basis for the clinical application of QSD.
基金by the Deanship of Graduate Studies and Scientific Research at Jouf University under grant No.DGSSR-2025-FC-01029.
摘要This article presents a Hierarchical Pathway-Masked Attention Autoencoder(H-PAAE),a biologically inspired representation-learning framework that enables explainable AI-guided cancer diagnosis.The model directly integrates the curated MSigDB Hallmark pathways,introducing pathway-constrained information flow and mechanistic interpretability through multi-level attention mechanisms.Based on TCGA RNA-seq data from 33 tumor types,H-PAAE compresses approximately 20,000 genes into a 128-dimensional latent space while preserving biologically meaningful structure.When used with XGBoost classification,H-PAAE delivers 92.37%test accuracy and 99.38%macro-AUROC with robust cross-validation results(92.5±0.6%).SHAP analysis identifies a small number of key latent features,corresponding to conserved oncogenic processes,and pathway enrichment analysis shows strong overlap with cancer hallmarks.H-PAAE provides a clear and interpretable biological foundation for pan-cancer classification,with well-calibrated posterior probabilities that can be used for clinical decision-making,and can be easily integrated into multimodal diagnostic workflows.
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).
摘要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 (Nos. 82204590 and 82560758)Jiangxi Provincial Natural Science Foundation (Nos. 20224BAB216099 and 20252BAC240467)+2 种基金China Postdoctoral Science Foundation (No.2023M731439)Key Technologies R&D Programme of Nanchang City (No. 2024zdxm023)Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program (No. CXTD22001)。
摘要Gouty arthritis(GA) is an inflammatory disorder characterized by the deposition of monosodium urate(MSU) crystals in joint tissues. Pulchinenoside B4(B4) has broad-spectrum antiinflammatory properties,but its role and potential mechanism in the pathogenesis of GA are still unclear. The purpose of this study is to comprehensively elucidate the therapeutic effect and mechanism of B4 on GA by integrating transcriptome analysis and in vitro and in vivo experiments. In the MSU-induced mouse GA model,B4 treatment significantly improved ankle edema and reduced inflammatory cell infiltration. Through the analysis of transcriptome sequencing results,we identified multiple differentially expressed long non-coding RNAs(lncRNAs),such as Nod1,Rbck1 and Pycard. In the in-depth exploration of the mechanism,we focused on the NOD-like receptor signaling pathway,NF-κB signaling cascade,and B4-regulated macrophage polarization. In vitro and in vivo models,we confirmed that B4 significantly inhibited the expression and activation of key components of NLRP3 inflammasome(such as ASC,Caspase-1 and IL-1β) by qPCR,Western blot and immunofluorescence. Flow cytometry and immunofluorescence analysis further showed that B4 could prevent MSU-induced macrophage polarization to pro-inflammatory M1 phenotype.Based on these results,this study elucidated the mechanism of B4 improving MSU-induced GA inflammatory response by inhibiting NLRP3 inflammasome activation and blocking M1 macrophage polarization. These results suggest that B4 has great potential as a candidate drug for the treatment of GA.
基金supported by Science and Technology Innovative Talent Program of Shaanxi University of Chinese Medicine(No.2024-CXTD-03)Key Research&Development Program of Shaanxi Provincial Department of Science and Technology(No.2024CY-JJQ-36,2024CY-JJQ-78)+4 种基金Shaanxi Provincial Administration of Traditional Chinese Medicine Research and Innovation Team Project(No.TZKN-CXTD-03)Youth Innovation Team of Aromatic Chinese Medicine Industrialization Key Technology(No.2022-95)Scientific Research Project of Shaanxi Administration of Traditional Chinese Medicine(ZYJXG-L23002)the Science and Technology Innovative Team Project of Shaanxi Administration of Traditional Chinese Medicine(No.2025-CXTD-02)The cartoon elements in the mechanism diagram are from http://gffzz287f705802804de1sw0p55xwpbq6c6vvn.ffgz.tsg.suse.edu.cn Provincial Science and Technology Department’s“two chains”integrated enterprise(institute)joint project(2023-LL-QY-39).
摘要Background:Cervicitis is a common gynecological disease,which triggers local inflammation and tissue damage by a complex mechanism,seriously affecting women’s health.Chinese medicine plays a prominent role in the treatment of gynecological inflammation.Shuangshi Tongling Capsule(SSTL),as a traditional Chinese medicine(TCM)compound,needs to be further elucidated for the treatment of cervicitis.Methods:Cervicitis was induced with 25%phenol gel(except controls),followed by 12-day intragastric treatment.Outcomes included genital inflammation scores,uterine index,and histopathology(HE staining).Serum tumor necrosis factor-α(TNF-α),Interleukin(IL)-6,IL-8,and IL-1βwere measured via ELISA.Integrated metabolomics-transcriptomics and Western blotting identified mechanistic pathways.Results:SSTL alleviated cervicitis in rats by improving uterine histopathology,reducing external genital inflammation scores(P<0.01 vs.model),and reversing uterine hypertrophy(P<0.05).Serum pro-inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-8)were suppressed(P<0.01),with concurrent weight restoration.Multi-omics analysis identified AMPK signaling as pivotal,validated by downregulation of p-NF-κB(P<0.05)and upregulation of p-AMPK/SIRT1(P<0.05)in uterine tissues,indicating SSTL mitigates inflammation through AMPK/NF-κB/SIRT1 modulation.Conclusion:This study found that SSTL ameliorates cervicitis in rats through the expression of AMPK pathway-related proteins.
基金Supported by Jiaxing Municipal Health Science and Technology Plan Key Project,No.JWKD-25010the Special Scientific Research Project of the Affiliated Hospital of Zhejiang Chinese Medical University,No.2024FSYYZQ17.
摘要Male infertility affects approximately 17.5%of the global reproductive-age population,with disruption of the testicular spermatogenic microenvironment-particularly the spermatogonial stem cell niche-representing a central pathogenic mechanism.Single-cell RNA sequencing has enabled unprecedented resolution of cellular heterogeneity within the human testis;however,its translational value remains constrained by population data imbalance and limited integration across molecular layers.Here,we synthesize single-cell RNA sequencing studies published between January 2018 and September 2025 to construct a microenvironment-centered mechanistic framework linking inflammaging,NLRP3 inflammasome activation,and progressive spermatogonial stem cell depletion in nonobstructive azoospermia,supported by convergent single-cell,bulk transcriptomic,and emerging preclinical evidence.We further discuss transgenerational epigenetic effects mediated by sperm small non-coding RNAs and critically evaluate translational barriers,including ancestry bias,technical limitations of singlecell platforms,and ethical challenges of germline intervention.We propose that future clinical translation will require multiethnic cohort construction and artificial intelligence-driven multi-omics integration to enable stem cell-oriented precision diagnosis and therapy for male infertility.
基金supported by the National Key Research&Development Program of China(2024YFC3405600 and 2022YFA1104200)the National Natural Science Foundation of China(22474075 and 22521102)+1 种基金the Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZLCX20212601)the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China(JYB2025XDXM507).
摘要Spatial transcriptomics(ST)is a powerful assay for capturing gene expression in tissues.However,due to inherent limitations of spatial resolution,most existing ST datasets remain at a multicellular resolution,which hinders a comprehensive understanding of spatial organization.We propose SpatioCell,a computational algorithm to automatically extract both cell type and expression information at single-cell resolution from ST data,through a morpho-transcriptomic spatial reconstruction framework solved via dynamic programming,integrating morphological and transcriptomic information.This framework enables deterministic single-cell spatial reconstruction,assigning cell identities to precise locations rather than inferring the spot-level cell type composition and expression.It further uncovers overlooked microenvironmental features while correcting deconvolution errors.Using ST data from triple-negative breast cancer as an example,SpatioCell reveals the significance of the distance between cancer-associated fibroblasts(CAFs)and tumor or immune cells in terms of disease progression.Thus,the establishment of SpatioCell will broaden the biomedical applications of ST and facilitate investigations of single-cell spatial organization.
摘要BACKGROUND Chronic hepatitis B(CHB)is a significant global health issue,and interferon(IFN)is one of the main first-line therapies for CHB.AIM To investigate the altered transcriptome,metabolites,and their correlations,as well as the effects and mechanisms of IFN treatment for CHB.METHODS The patients received peginterferon alfa-2b at a dose of 180μg for 0,1,3,and 6 months and serum samples were collected for clinical biological assays,transcriptomics,and metabolomics analyses.RESULTS The results showed that IFN-related immune pathways and neutrophil extracellular traps(NETs)were the most significantly altered pathways following IFN treatment.Correlation analysis revealed a strong link between immune system-related genes in the transcriptome and dipeptides in the metabolome during IFN-αtreatment.Notably,core components of NETs,including histones H2A clustered histone 14,H2B clustered histone 5,H3 clustered histone 1,and H4 clustered histone 4,were significantly increased after IFN treatment.The positively charged histones may bind to the negatively charged viral envelope,potentially enhancing the antiviral effect.CONCLUSION Integrated non-targeted transcriptomic and metabolomic analyses to CHB patients undergoing IFN-αtreatment revealed that IFN-related immune pathways and NETs were the most significantly affected pathways during IFN treatment.These findings provide a deeper understanding of the role of NETs and dipeptides in the antiviral response to IFN treatment for CHB.
基金supported by grants from the National Research Foundation of Korea(2023R1A2C2003958 to S.W.K.)Boramae Medical Center(02-2020-9 to S.W.K and S.K)+2 种基金the Korea-US Collaborative Research Fund(KUCRF),funded by the Ministry of Science and ICT and Ministry of Health&Welfare,Republic of Korea(RS2024-00508416)the Industrial Strategic Technology Development Program funded by the Ministry of Trade Industry&Energy(MOTIE)of Republic of Korea(RS-2024-00508416 to S.K.)the BK21 FOUR program of the Education and Research Program for Future ICT Pioneers(Seoul National University in 2025)。
摘要Dynamic transitions of mature osteoblasts between active and quiescent states are essential for bone homeostasis and present a promising target for osteoanabolic therapy.However,these transitions remain poorly understood due to cellular heterogeneity and limited spatial context.Here,we employed spatially resolved osteoblast-traced transcriptomics,integrating an osteoblast-specific lineage tracing study and spatially resolved laser-activated cell sorting(SLACS),to profile osteoblast states on quiescent bone surfaces.This approach identified transforming growth factor-beta(TGF-β)signaling as a regulator of osteoblast activation.We further validated this role using single-cell RNA sequencing,in vitro functional assays,and in vivo.In a hindlimb unloading mouse model,dual inhibition of TGF-βand sclerostin enhanced bone mass and mitigated bone loss more effectively than sclerostin inhibition alone.These findings reveal a mechanistic role for TGF-βin regulating osteoblast dynamics and propose a dual-target therapeutic strategy that enhances the efficacy of anti-sclerostin treatment in osteoporosis.
摘要OBJECTIVE To investigate the therapeutic effects of Xianlian Jiedu Decoction(XLJDD)on colitis-associated colorectal cancer(CAC)and to explore its potential underlying mechanisms.METHODS An azoxymethane/dextran sulfate sodium(AOM/DSS)-induced CAC mouse model was established.UPLC-Q-TOF/MS was employed to identify prototype compounds present in colonic tissue after XLJDD administration.Network pharmacology analysis,molecular docking,transcriptomic sequencing,and valida‑tion of key pathway-related genes were further conducted to systematically elucidate the intervention effects and potential mechanisms of XLJDD against CAC.RESULTS In the AOM/DSS-induced CAC mouse model,XLJDD treatment markedly improved tumor-associated pathological features,as evidenced by reduced tumor burden,restored colon length,and alleviated disease activity index(DAI).UPLC-Q-TOF/MS analysis identified 22 exogenous compounds derived from XLJDD in colonic tissue.In addition,XLJDD sig‑nificantly downregulated the expression of multiple inflammatory cytokines while upregulating tight junction-related genes in the co‑lon.Transcriptomic analysis revealed that XLJDD treatment enhanced overall PPAR signaling pathway activity while suppressing the Wnt signaling pathway.Consistently,the expression levels of PPAR pathway-related genes Pparα,Cpt1a,and Ehhadh were upregulated following XLJDD intervention(P<0.05,P<0.01),whereas the Wnt pathway-related genes Axin2 and Lef1 were significantly downregulated(P<0.05,P<0.01).CONCLUSION XLJDD may intervene in inflammation-associated colorectal carcinogenesis by activating the PPAR signaling pathway and suppressing the Wnt signaling pathway.
基金supported by grants from the Core Program grants of Guizhou Province,China(Grant No.QKHZDZXZ[2024]28)the Guizhou Provincial Science and Technology Projects of China(Grant No.YQK[2023]008)the Guizhou Provincial Scientific and Technological Program(Grant No.QKHFQ[2024]004-1).
摘要Blueberry(Vaccinium ashei)is highly characterized by its nutritional value,with an extremely high anthocyanin content,and rabbiteye blueberry is widely grown across China.However,molecular regulatory mechanisms underlying the high anthocyanin accumulation during the fruit development and colouration of rabbiteye blueberry fruit,have not yet been fully clarified so far.The fruit anthocyanin content of rabbiteye blueberry in the karstic area of Guizhou Province,China,is much higher compared to that in other regions,and the fruit colour is highly affected by anthocyanin accumulation.Currently,the untargeted metabolomics and HPLC assays have been carried out using rabbiteye blueberry fruit at various stages,and it was investigated that cyanidin(Cy)and pelargonidin(Pg)reached their peaks at the red fruit(RF)stage,whereas delphinidin(Dp),petudinin(Pt),malvidin(Mv),and peonidin(Pn)got their ceilings at the mature fruit(MF)stage.Transcriptome and co-expression network analyses showed that 27 differentially expressed genes(DEGs)were associated with anthocyanin content,among which VdMYB56,belonging to the R2R3-MYB family,was markedly up-regulated during the development and colouration of fruit,and was significantly higher in the skin than in the pulp.Furthermore,VdMYB56-overexpressing tomato fruits demonstrated a substantial elevation in anthocyanin content on the 35th day after flowering(DAF).It was worth noting that VdMYB56 could directly bind to the promoter of Vd3GT to enhance its expression,thereby further strengthening the anthocyanin accumulation.Meantime,multiple assays verified that VdMYB69,an R2R3-MYB member,might interact with VdMYB56,leading to the promotion of VdMYB56 expression.Conclusively,the VdMYB56-VdMYB69 module is a positive regulator of anthocyanin biosynthesis in rabbiteye blueberry,which may provide new insights into high-anthocyanin breeding,particularly for the southern karstic regions.
基金financially supported by the Science and Technology Project of Nantong City(Grant No.JC2021097)the Key Project Fund for Clinical Medicine Special Program of Nantong University(Grant No.2024JZ043)Jiangsu Provincial Administration for Market Regulation Science and Technology Program Project(Grant No.KJ2026104).
摘要Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.
基金supported by Biological Breeding-Major Projects to Yun Ma(Grant No.2023ZD0404803)Key R&D Program of Ningxia Hui Autonomous Region to Lingkai Zhang(2023BBF01007)and(2023BCF01006)。
摘要Background Mammalian spermatogenesis is critical for the transmission of male genetic information,and singlecell sequencing technology can reveal its complex process.However,at present,there is no research on the dynamic transcription of bovine germ cell population.Results In this study,we used Stereo-seq to construct a spatial transcription map of bovine testicular tissue at two ages.Four germ cell groups and five somatic cell groups were determined,and functional enrichment characterized their different biological functions and the differences between calves and adult bulls.At the same time,we also defined the subpopulations of cells and marker genes,then,clarified the communications between germ cells.Conclusion Our study constructed a spatial transcription map of bovine testicular tissue for the first time,and systematically described the dynamic transcription changes during spermatogenesis.These data laid the foundation for the study of spermatogenesis in large mammals and elucidated the transcriptional dynamics underlying male germ cell development.
基金supported by the financial support from the Major Science and Technology Special Project of Yunnan Province(Grant No.202202AG050021)National Science Foundation of China(Grant No.32360151).
摘要Root tips,which represent the initial stage of taproot development,serve as an ideal model for investigating plant growth and secondary metabolism.However,studies of root tips in Panax species have been limited,restricting our understanding of cell fate transitions during early root development and the cellular heterogeneity associated with ginsenosides biosynthesis.To address this gap,we conducted single-cell RNA sequencing(scRNA-seq)and spatial metabolomics analyses on the root tips of three Panax species:Panax notoginseng,Panax ginseng,and Panax quinquefolium.Our research reconstructed the developmental trajectory of the early endodermis and revealed epidermis-specific expression patterns of key enzyme genes involved in ginsenosides biosynthesis.We identified several novel transcription factors(TFs):IAA29(which positively regulates endodermis suberization)and MYB2/MYB78(positive regulators of ginsenosides biosynthesis),validated by dual-LUC reporter and electrophoretic mobility shift assay(EMSA).Conserved and divergent ligand-receptor interaction patterns across the three Panax species were discovered,with the FAD gene family exhibiting tissue-and species-specific expression.Cell-specific genes expression was confirmed by RNA in situ hybridization.Mass spectrometry imaging(MSI)mapped ginsenosides spatial distribution,while LC–MS/MS verified species-specific biosynthesis.This study presents a singlecell transcriptional landscape of early differentiation and cell type-specific ginsenosides accumulation in the Panax genus.
基金supported by the National Natural Science Foundation of China,No.82301403(to DZ)。
摘要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-CO2 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.