Search Results (3,467)

Background: Su(var)3-9 SET genes encode key histone methyltransferases that catalyze H3K9 methylation, a modification generally associated with heterochromatin formation and transcriptional repression. Methods: We identified 23 GmSu(var)3-9 SETs and systematically characterized their tissue-specific epigenetic modifications as well as their phylogenetic relationships, chromosomal distributions, conserved domains, gene structures, GO annotations, collinearity, cis-regulatory elements, and expression profiles across diverse tissues and under salt stress. Results: These genes were divided into seven groups, exhibiting diverse structures and uneven distribution on chromosomes. Gene structure and conserved motif analyses revealed high structural diversity among family members, with variations in intron–exon distribution, conserved motifs, and functional domains. Promoter analysis detected multiple cis elements responsive to light, hormones, and abiotic stresses. Most genes showed preferential expression in meristems, roots, and leaves, and responded to salt stress. Co-expression network analysis revealed that these genes were co-expressed with stress- and development-related genes. GmSUVH12 histone modifications exhibited obvious tissue specificity. Conclusions: Overall, these results provided insights into the evolutionary and functional roles of GmSu(var)3-9 SETs in soybean. Full article

This paper introduces an approach for inferring the gene regulatory networks in vortioxetine-induced glioblastoma cells to investigate vortioxetine’s systemic effects. The approach uses an ordinary differential equation (ODE)-based inverse problem to evaluate the drug-induced gene interactions within the GLIOMA and ERBB pathways, which are deeply intertwined in cancers, by using time-series datasets. Time-series datasets were generated in triplicate at 0, 3, 6, 9, 12, and 24 h. The results of the ERBB pathway confirmed that PIK3R5 was commonly activated, while JUN, as a proto-oncogene in glioblastoma, was inhibited by genes across all three datasets. In particular, PIK3R5 was commonly activated by PAK6 in all three datasets. The results of the GLIOMA pathway confirmed that CALML6 was commonly activated, while CDK4 and CCND1, which are mostly overexpressed in human cancers, were inhibited across all three datasets. Additionally, an analysis of the independent datasets generated at 6 and 22 h after the vortioxetine injection identified the most distinct variable genes between the two time points: CRK (1.96) and JUN (−3.02) for the ERBB signaling pathway, and BRAF (1.30) and MAP2K2 (−1.92) for the GLIOMA pathway. We conclude that vortioxetine, an antidepressant, decreases JUN, a proto-oncogene involved in the ERBB signaling pathway, and CCND1, another proto-oncogene involved in the GLIOMA pathway, over time in glioblastoma cells. Full article

Schwann cells, the principal glial cells of the peripheral nervous system, play a central role in nerve repair following injury. Upon injury, mature Schwann cells dedifferentiate into repair Schwann cells. These processes are governed by complex gene regulatory networks, yet the quantitative dynamics of these processes remain unclear. Here, using a bottom-up systems biology approach, we constructed an endogenous regulatory network model based on experimentally validated interactions, without relying on high-throughput data as input. The model captures Schwann cell dedifferentiation dynamics and reveals a potential landscape composed of stable states and intermediate transition states. Simulations recapitulate post-injury trajectories and confirm the role of c-Jun upregulation in maintaining repair capacity. Furthermore, the model predicts multiple potential therapeutic targets, including tumor protein p53 (P53), c-Jun N-terminal kinase (JNK), and phosphatase and tensin homolog (PTEN), for sustaining repair competence. We also identify intrinsic heterogeneity within repair Schwann cells. Furthermore, we uncover key transition states that simultaneously connect repair-competent cells to both repair-deficient and apoptotic phenotypes. These intermediate states may represent critical regulatory bottlenecks and serve as key cellular targets for improving peripheral nerve regeneration. Overall, this work provides new insights into the precise regulation of Schwann cell fate and establishes a theoretical framework for regenerative medicine and clinical strategies in peripheral nerve repair. Full article

Background: Chronic atrophic gastritis (CAG) is a prevalent precancerous gastric disorder characterized by persistent inflammation, glandular atrophy, and progressive mucosal damage, for which effective multi-target therapeutic strategies remain insufficient. The Lian-Huo-Hua-Zhuo formula (LHHZ), a traditional Chinese herbal prescription, has demonstrated potential anti-inflammatory and gastrointestinal protective effects in clinical practice; however, its active constituents and mechanisms of action against CAG remain undefined. This study aimed to clarify the absorbed bioactive components of LHHZ and explore its therapeutic mechanism for CAG. Methods: Ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was employed to identify the absorbed components of LHHZ in the gastric and intestinal tissues of mice. The therapeutic effects of LHHZ on CAG were assessed through histopathological staining, ultrastructural observation, and evaluation of serum and gastric functional indicators. Network pharmacology, molecular docking, and molecular dynamics simulations were integrated to predict the core targets and key signaling pathways, while the regulatory effects on the interleukin-17 (IL-17) signaling pathway were further validated by immunofluorescence staining, real-time quantitative polymerase chain reaction, and Western blotting. Additionally, 16S ribosomal RNA gene sequencing and targeted metabolomics were applied to investigate the effects of LHHZ on gut microbiota composition and short-chain fatty acid (SCFA) metabolism. Results: The results revealed that 55 and 48 absorbed components were identified in the gastric and intestinal tissues, respectively, predominantly derived from Coptis chinensis Franch. and Pogostemon cablin (Blanco) Benth. LHHZ significantly alleviated gastric mucosal lesions, reduced intestinal metaplasia, restored the ultrastructure of gastric mucosal cells, improved gastric functional indicators including pepsinogen I (PG I), pepsinogen II (PG II), and gastrin-17 (GAS-17), and decreased the levels of pro-inflammatory cytokines. Network pharmacology combined with in vitro and in vivo experiments demonstrated that the core bioactive components of LHHZ can target and regulate interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), attenuate activation of the IL-17 signaling pathway, and suppress the secretion of downstream pro-inflammatory factors. Furthermore, LHHZ enhanced the alpha diversity of gut microbiota, reduced the Firmicutes to Bacteroidetes (F/B) ratio, restored the abundance of SCFA-producing bacteria such as Bacteroidales and Oscillospirales, and normalized the aberrant levels of eight SCFAs. Significant correlations were also observed between gut microbiota composition and SCFA metabolism. Conclusions: These findings suggest that LHHZ alleviates CAG by inhibiting inflammation via the IL-17 signaling pathway and by modulating the gut microbiota–SCFA axis, thereby providing preclinical evidence supporting its further investigation and development for multi-target therapeutic strategies against CAG. Full article

Cannabis sativa L. is an economically significant multi-use crop valued for fiber, seed, and phytochemical production. Compared with other crops, advancement in Cannabis sativa has been slow due to regulatory constraints and genetic resource limitations. Recent advances in technology have transformed the research landscape, supporting a deeper understanding of the genetic architecture underlying key agronomic traits. This review summarizes current progress in Cannabis sativa genetics and genomics, mainly focusing on structural genome organization, including chromosome-level assemblies and emerging pangenomic resources that capture species-wide diversity. We explore the molecular basis of key agronomic traits, including sex determination, cannabinoid biosynthesis, fiber quality, seed composition, disease resistance, and abiotic stress tolerance, highlighting their complex regulatory networks. Functional genomics tools including virus-induced gene silencing, transient expression systems, and CRISPR/Cas9 genome editing are reviewed as approaches enabling direct gene functional validation. We further review integration of these resources with molecular breeding strategies, including marker-assisted and genomic selection, to accelerate elite genotype development. Finally, we address persistent challenges such as genomic complexity, reference bias, and phenotyping limitations while outlining future research directions. Together, these advances position C. sativa as a compelling system for both fundamental plant biology and applied crop improvement. Full article

An 8-week feeding trial was conducted to investigate the regulatory effects of dietary chitosan oligosaccharide (COS), chlorogenic acid (CGA), and thymopeptide (TH) on the growth performance, antioxidant capacity, and metabolism of juvenile Rhinogobio ventralis. A control group (CON) and three treatment groups (COS, CGA, TH) were established, and the underlying molecular mechanisms were analyzed by transcriptomics and metabolomics. The results showed that dietary supplementation with COS, CGA, and TH significantly improved weight gain rate, specific growth rate, and feed utilization efficiency, with COS exhibiting the strongest growth-promoting effect. COS also significantly increased hepatic catalase and superoxide dismutase activities and decreased malondialdehyde content, indicating a marked antioxidant effect, whereas CGA and TH showed no significant effects on these parameters. Transcriptomic analysis revealed significant differences in gene expression profiles among the groups, with commonly enriched pathways including the FoxO signaling pathway, fatty acid biosynthesis, and nicotinate and nicotinamide metabolism. Metabolomic analysis showed that the three additives significantly reshaped the hepatic metabolic profiles: COS mainly activated anabolic metabolism, CGA predominantly suppressed metabolism, and TH exhibited bidirectional regulation, with bile secretion, neuroactive ligand–receptor interaction, and the Fc epsilon RI signaling pathway commonly enriched in all three groups. Integrative KEGG pathway analysis based on transcriptomic and metabolomic predictions further identified the FoxO signaling pathway and neuroactive ligand–receptor interaction as common targets shared by all three additives. In conclusion, COS, CGA, and TH improve the health status of R. ventralis through differential regulation of immune–metabolic networks. Among them, COS is the most suitable feed additive for growth promotion and antioxidant protection in this species. Full article

GRAS transcription factors are crucial regulators governing plant growth and stress adaptation, yet no systematic genome-wide investigation of the GRAS gene family has been reported for coriander, celery and carrot, three economically and medicinally important Apiaceae vegetables, which creates a critical research gap for comparative and functional genomics in Apiales. Here, we performed a multi-tiered bioinformatic pipeline integrating gene identification, phylogenetic classification, chromosomal mapping, gene duplication analysis, transcriptome profiling, co-expression network construction and large-scale evolutionary tracing across 406 plant genomes. In total, 87, 74 and 74 GRAS genes were identified from coriander, celery and carrot, respectively, which were divided into 13 subfamilies. WGD/segmental duplication drove GRAS expansion in coriander and carrot, while dispersed duplication dominated in celery. Tissue-specific expression and cross-TF regulatory networks uncovered core GRAS hub genes participating in developmental and stress pathways. Wide-range phylogeny further validated that GRAS genes originated from Zygnematophyceae algae and massively expanded in Penium margaritaceum. This study fills the research gap of GRAS family analysis in Apiaceae, provides abundant high-throughput data resources, and offers fundamental evolutionary clues for future functional verification and genetic improvement of horticultural crops. Full article

Background: Coarctation of the aorta (CoA) is a congenital narrowing of the aortic isthmus near the ductus arteriosus or ligamentum arteriosum. Despite successful anatomical repair, patients remain at risk of recoarctation, arterial hypertension, and diffuse aortopathy, suggesting intrinsic vessel-wall abnormalities beyond localized obstruction. The developmental and molecular basis of these persistent vascular features remains incompletely understood. Methods: Human aortic tissue samples were obtained from 8 male infants with CoA and 6 age- and sex-matched controls aged <1 year. Total RNA was isolated, and gene expression profiling was performed using whole human genome oligo microarrays (Agilent). Differentially expressed transcripts were subjected to pathway, network, and upstream regulator analyses using Ingenuity Pathway Analysis (IPA, Qiagen). Selected candidate genes were evaluated by RT-qPCR in independent verification sets. Results: Transcriptomic profiling identified 402 analysis-ready transcripts distinguishing CoA from control tissue. Exploratory pathway analyses suggested extracellular matrix remodeling characterized by collagen turnover, integrin-mediated cell–matrix interactions, wound-healing signaling, and fibrosis-associated programs. In addition, enrichment analyses identified developmental annotations involving retinoic acid (RA)/RAR/RXR signaling, HOX-associated developmental programs, and a shared HOX/MEIS-associated signature. Network and upstream regulator analyses further suggested associations with cytoskeletal, muscle-associated, and epigenetic regulatory pathways, including KAT6A, KAT6B, retinoic acid/RAR/RXR signaling, DNMT3B, KMT2A, and ARID1A. RT-qPCR independently confirmed increased expression of EDN1, AGTR2, IRS4, and TFAP2B. Conclusions: Infantile CoA tissue exhibited molecular signatures consistent with vessel-wall remodeling accompanied by developmental, vascular signaling, and smooth muscle/cytoskeletal regulatory programs. These findings support the hypothesis that developmental patterning signals and postnatal extracellular matrix remodeling coexist within CoA tissue and may contribute to persistent vascular abnormalities beyond anatomical repair. Given the exploratory nature of the study, these observations should be considered hypothesis-generating and require validation in independent cohorts. Full article

Cyclin-dependent kinases (CDKs) and cyclins are master regulators of the cell cycle, playing critical roles in plant growth, development, and stress responses. While these gene families have been extensively studied in model plants, a comprehensive analysis in soybean remains underexplored. To address this gap, we performed a genome-wide identification and systematic analysis of these families in soybean using bioinformatic approaches. Expression profiles and protein interactions of selected GmCDK and GmCyclin candidates were tested by qRT-PCR and BiFC assays. A total of 28 GmCDK and 101 GmCyclin genes were identified, revealing a significant expansion compared to Arabidopsis, rice, and maize, primarily driven by whole-genome and segmental duplications. Phylogenetic analysis classified GmCDKs into seven conserved clades (CDKA-CDKG) and GmCyclins into ten distinct subfamilies. Expression profiling demonstrated dynamic, tissue-specific patterns, with distinct modules active during seed development and in tissues. Promoter analysis further linked these genes to hormonal and stress-responsive pathways. Crucially, BiFC assay identified specific interactions between GmCDKA2, GmCDKA3, GmCDKB1 and GmCYCA3-3, suggesting evolutionary divergence in soybean CDK-Cyclin regulatory networks. This study provides a foundational resource for the soybean cell cycle regulome, highlighting its evolutionary plasticity and implicating specific CDK-Cyclin pairs as potential targets for manipulating agronomic traits such as seed development and stress resilience. Full article

Histone deacetylases (HDACs) are important epigenetic regulatory enzymes contributing to cancer proliferation, which could be critical targets in cancer therapy. The structural similarities of the existing HDAC inhibitors have resulted in an increase in the drug resistance. In this study, coumarin was employed as the core scaffold for structural derivatisation to develop a novel class of HDAC inhibitors based on computer-aided design (CADD). Their anti-tumor activity was evaluated against esophageal squamous cell lines. The results showed that most compounds exhibited potent anti-proliferative activity against KYSE70 and KYSE150. Among them, compound 4s and 4p exhibited the most potent activity with IC₅₀ values of 3.44 μM and 3.39 μM against KYSE70. To validate the target of the synthesized compounds, transcriptome sequencing was performed and the results revealed that a total of 487 genes were differentially expressed, including 190 up-regulated and 297 down-regulated genes. Among these, 79 genes were associated with the HDAC regulatory network, accounting for 16.2% of the differentially expressed genes. Molecular docking demonstrated that compound 4s could effectively enter the active site of HDAC, engaging with the cap group, zinc-binding group, and linker region. This multiple interaction network provides a structural basis for the potent inhibitory activity of compound 4s. In conclusion, a series of novel HDAC inhibitors with a coumarin scaffold were discovered, and their mode of action was revealed. This provides a valuable guide for the development of novel HDAC-targeting therapeutics. Full article

Background/Objectives: Atherosclerotic plaque instability is driven by complex interactions among inflammatory, structural, and cellular remodeling programs. While bulk RNA sequencing provides insight into tissue-level transcriptional states and single-cell RNA sequencing (scRNA-seq) defines cellular heterogeneity, integration across these transcriptomic layers remains limited. We aimed to identify coordinated transcriptional programs associated with stable and unstable plaque phenotypes and map these programs to specific cellular compartments and regulatory networks. Methods: Paired bulk RNA-seq data from stable and unstable human carotid plaques (GSE120521) and scRNA-seq data from human coronary atherosclerotic lesions (GSE131778) were analyzed. Differential expression and Hallmark gene set enrichment analyses were performed using limma and clusterProfiler. Bulk-derived inflammatory and structural signatures were projected onto single-cell data using Seurat module scoring. Compartment-level transcriptional scores, an inflammatory–structural endotype index, and transcription factor activity inference using decoupleR and DoRothEA were used to characterize plaque-associated transcriptional states. Results: Unstable plaques demonstrated enrichment of inflammatory pathways, including interferon gamma response, inflammatory response, TNFα/NF-κB signaling, IL6/JAK/STAT3 signaling, complement activation, and reactive oxygen species pathways. In contrast, stable plaques demonstrated relative enrichment of myogenesis and structural remodeling programs. Projection of bulk-derived signatures onto single-cell data localized inflammatory programs predominantly to TREM2hi and inflammatory macrophage populations, whereas structural programs localized to smooth muscle cell and fibromyocyte-like compartments. Compartment-level analyses showed increased myeloid and adaptive immune signatures in unstable plaques and increased smooth muscle cell/fibro-remodeling signatures in stable plaques. Transcription factor activity analysis identified increased SPI1, NFKB1, RELA, and STAT1 activity in unstable plaques and higher SRF and TEAD1 activity in stable plaques. Conclusions: Integrative analysis of bulk and single-cell transcriptomic data identified distinct inflammatory and structural plaque transcriptional states associated with unstable and stable plaque phenotypes, respectively. These findings support a systems-level framework linking tissue-level plaque behavior to specific cellular and regulatory programs and provide evidence for inflammatory and structural plaque endotypes in human atherosclerosis. Full article

Lilac (Syringa oblata Lindl.) is an important eco-economic aromatic shrub in northern China; however, the key volatile organic compounds (VOCs) responsible for its floral aroma and their origin remain largely unexplored. In this study, we conducted an integrated analysis of volatile metabolomics and transcriptomics to elucidate the composition, dynamic changes, and potential regulatory network of VOCs across different floral organs and petal developmental stages. A total of 1440 VOCs were identified in the stamens, pistils, and petals, with petals being the primary contributors to the overall floral aroma. Analysis of different petal developmental stages revealed that the full-bloom stage (S3) is critical for VOCs emission. The floral aroma of S. oblata is primarily composed of terpenoids, alcohols, and aldehydes. By relative odor activity value (rOAV) with multivariate statistical screening, seven key VOCs with high contributions to the floral aroma were identified. Transcriptome analysis identified 69,935 differentially expressed genes (DEGs) across petal developmental stages, which were predominantly enriched in metabolic pathways and the biosynthesis of secondary metabolites. The expression patterns of these DEGs were highly consistent with the accumulation trends of VOCs, increasing at stages S2 and S3 and subsequently declining at stage S4. Integrative analysis of VOCs and gene expression further identified candidate genes significantly correlated with the key aroma volatiles. Specifically, the carotenoid pathway-related genes CYP97A3 and LYC may influence the formation of carotenoid-derived volatiles and floral aroma. Additionally, genes associated with the fatty acid-lipoxygenase pathway, transport-related genes, and transcription factors are potentially involved in the formation and regulation of aldehyde and alcohol volatiles. These findings advance our understanding of the floral aroma formation in S. oblata and provide metabolic basis, candidate gene resources and a theoretical foundation for the genetic improvement of aroma traits and the breeding of new cultivars. Full article

The pituitary and gonads serve as central regulatory hubs and functional organs for gametogenesis and maturation. In this study, we performed single-cell RNA sequencing (scRNA-seq) of the pituitary and ovary in pre-spawning Pelteobagrus fulvidraco to elucidate the cellular landscape and regulatory pathways governing gonadal development and oocyte maturation. Pituitaries from four female fish (weight: 43.8 ± 3.2 g; length: 14.1 ± 0.7 cm) and four male fish (weight: 78.2 ± 11.2 g; length: 18.9 ± 1.1 cm) were subjected to single-cell transcriptomic analysis. A total of 17 distinct cell types were identified in the female pituitary, whereas 15 cell types were detected in the male pituitary. Both male and female pituitaries comprised multiple hormone-secreting endocrine populations, indicating a largely conserved cellular composition. However, sex-specific differences were observed in thyrotrope subtypes, suggesting potential sexual dimorphism in pituitary endocrine regulation. Examination of receptor gene expression revealed cell-type-specific regulatory capacities, highlighting gonadotropin, steroid, and neuropeptide responsiveness across pituitary populations. In the ovary, 10 cell types were identified, with granulosa cells (~22.9%) and theca cells (~8.6%) showing distinct transcriptional profiles. Follicle-stimulating hormone receptor (fshr) was highly expressed in granulosa cells, whereas luteinizing hormone receptor (lhcgr) and steroidogenic genes (hsd3b1, pgr) were predominantly localized in theca cells, indicating functional compartmentalization of gonadotropin and steroid signaling. Prostaglandin (PG) and melatonin (MT) pathways were implicated in paracrine regulation: the prostaglandin synthase ptgs2a was expressed in theca, germ, and immune cells, while ptger2a was expressed in granulosa cells; melatonin synthesis genes (aanat1, aanat2, asmtl) were confined to granulosa cells, with receptors (mtnr1ab) in germ cells. These findings suggest that ovarian paracrine signaling complements systemic endocrine control to modulate oocyte maturation and ovulation. This single-cell atlas provides a high-resolution framework of reproductive cell types and signaling networks in P. fulvidraco, offering insights for improving artificial breeding and reproductive management in aquaculture. Full article

CD8⁺ T-cell exhaustion is a key mechanism of tumor immune evasion and a major limitation of current cancer immunotherapy. However, the molecular factors sustaining dysfunctional CD8⁺ T-cell states across cancers are not fully understood. Here, we identify GPR171 as a common feature of exhausted CD8⁺ T cells across multiple solid tumors based on integrated pan-cancer single-cell transcriptomic analyses. GPR171 is enriched in exhausted CD8⁺ T cells and is closely associated with immunosuppressive and exhaustion-related gene programs. It also shows a strong association with key immune regulatory genes such as CTLA4 and NR4A2. Functional analyses suggest that reduced GPR171 activity is associated with decreased expression of exhaustion-related genes and a shift toward cytotoxic and immune-activating programs. In parallel, a CREM-centered regulatory network emerges in exhausted CD8⁺ T cells and may act in concert with GPR171-associated programs to reinforce dysfunctional states. Overall, our results identify GPR171 as a candidate marker of CD8⁺ T-cell dysfunction across cancers and provide a systematic pan-cancer single-cell characterization of its association with immunosuppressive T-cell states, supporting its potential as a therapeutic target for restoring antitumor immunity. Full article

Background/Objectives: Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is implicated in the pathogenesis of ulcerative colitis (UC). Tryptophan metabolism and its interaction with the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2–related factor 2 (Nrf2) axis represent a crucial regulatory network in intestinal homeostasis. This study aimed to investigate whether the probiotic fermentation product postbiotic Nagqu4580 alleviates UC by modulating this network to inhibit intestinal epithelial ferroptosis. Methods: An acute UC model was induced in mice using 4% dextran sodium sulfate (DSS). The therapeutic effects of postbiotic Nagqu4580 were evaluated through disease activity index (DAI), colon length, histopathology, inflammatory cytokines, and intestinal barrier function. Ferroptosis was assessed by measuring lipid peroxidation (MDA, 4-HNE), antioxidant capacity (GSH/GSSG), and expression levels of GPX4 and ACSL4. Serum tryptophan metabolites were profiled using targeted metabolomics, the activation of the AhR/Nrf2 pathway was examined by Western blot, immunofluorescence, and qPCR, and gut microbiota composition was analyzed by 16S rRNA sequencing. Results: Postbiotic Nagqu4580 dose-dependently ameliorated DSS-induced UC in mice, as evidenced by reduced DAI scores, mitigated colon shortening and histological damage, decreased inflammatory cytokines (TNF-α, IL-1β, IL-6), and restored intestinal barrier function by upregulating tight junction proteins (Claudin-1, ZO-1, Occludin). Mechanistically, postbiotic Nagqu4580 inhibited intestinal epithelial ferroptosis by reducing MDA and 4-HNE levels, restoring the GSH/GSSG balance, downregulating ACSL4, and upregulating GPX4. Serum metabolomics revealed that postbiotic Nagqu4580 reshaped tryptophan metabolism, increasing beneficial metabolites such as 5-hydroxyindoleacetic acid (5-HIAA) and decreasing potentially harmful metabolites such as 3-indoxyl sulfate (3-IS). 16S rRNA sequencing further revealed that the postbiotic Nagqu4580 partially reversed DSS-induced gut microbiota dysbiosis, with a slight increase in the abundance of beneficial genera and a significant reduction in the abundance of pro-inflammatory genera. Furthermore, postbiotic Nagqu4580 significantly activated the AhR/Nrf2 signaling pathway, enhancing the expression of AhR, Nrf2, and their downstream antioxidant genes HO-1 and GPX4. Conclusions: Postbiotic Nagqu4580 alleviates UC by inhibiting intestinal epithelial ferroptosis. Our data suggest that this protective effect is associated with the remodeling of gut microbiota-related tryptophan metabolism and subsequent activation of the AhR/Nrf2 antioxidant axis. Our findings highlight the therapeutic potential of postbiotic Nagqu4580 as a postbiotic agent for UC. Full article