Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe bone disease associated with long-term glucocorticoid use, characterized by impaired bone metabolism and vascular insufficiency. Bilobalide (BB), a natural sesquiterpene from Ginkgo biloba, exhibits anti-apoptotic, antioxidant, and pro-angiogenic properties, yet its role in SONFH remains unclear. We integrated network pharmacology and molecular docking to predict the targets and pathways of BB in SONFH. Key targets were validated using molecular docking software. For in vivo experiments, a rat SONFH model was established using methylprednisolone (MPS), and BB was administered orally. Micro-CT, H&E staining, TUNEL assay, and immunohistochemistry were employed to evaluate bone microstructure, apoptosis, and the expression of osteogenic and angiogenic markers. Immunofluorescence was used to assess HIF-1α expression in rat femoral head tissues. For in vitro experiments, MC3T3-E1 osteoblasts were treated with dexamethasone(DEX) and BB. Cell viability was detected using the CCK-8 assay, and the protein levels of the HIF-1α and ERK pathways were examined by Western blot. Network pharmacology identified 94 common targets between BB and SONFH, with enrichment in HIF-1 and ERK signaling pathways. Molecular docking confirmed strong binding affinities between BB and core targets. In MPS-induced rats, BB treatment significantly improved bone mineral density, trabecular microstructure, and reduced osteocyte apoptosis. BB also upregulated HIF-1α, Runx2, OCN, CD31, and VEGF expression, indicating enhanced osteogenesis and angiogenesis. In vitro, BB rescued dexamethasone-induced suppression of osteoblast viability and upregulated the ERK/HIF-1α pathway. Bilobalide attenuates SONFH progression by activating the ERK/HIF-1α signaling pathway, promoting osteogenesis and angiogenesis, and reducing osteocyte apoptosis. These findings highlight BB as a promising candidate for SONFH prevention and support the utility of network pharmacology in mechanistic natural product research.

Understanding how immune cell programs diverge between active tuberculosis (TB) and latent tuberculosis infection (LTB) is essential for improving diagnosis and treatment. Here, we performed a large-scale, full-length, splicing-resolved transcriptomic analysis across 16 purified immune cell types using mini-bulk RNA sequencing. The dataset comprised 2,578 profiles from 43 TB patients, 11 individuals with LTB, and 31 healthy controls, together with longitudinal follow-up data from 10 TB patients during treatment. Analysis of immune cell composition identified increased frequencies of granulocytes, intermediate monocytes, Th17 cells, and regulatory T cells in active TB compared with healthy controls. Beyond cellular composition, alternative splicing (AS) emerged as a major regulatory layer, with T cell subsets exhibiting extensive splicing alterations both during disease and following treatment. Distinct cell-type-specific splicing signatures differentiated TB from LTB, including differential isoform usage of IFNGR1, guanylate-binding proteins, caspases, and gasdermin D along interferon-γ and cell-death-related pathways. These splicing alterations were partially reversed during anti-TB treatment, indicating dynamic regulation linked to disease state. Together, this study defines a splicing-resolved, cell-type-specific immune landscape of TB and reveals AS as a key regulatory mechanism shaping immune dysfunction and recovery during infection and treatment immune.

To assess the potential of urinary exosomal miRNA as a predictor of kidney scarring in children with vesicoureteral reflux (VUR). A prospective study was conducted in pediatrics diagnosed with VUR between September 2023 to December 2025. Urinary exosomes were isolated from patients via ultracentrifugation and subsequently characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot. The expression levels of exosomal miRNAs were profiled using miRNA sequencing and validated by quantitative real-time PCR. Kidney scarring was determined based on dimercaptosuccinic acid (DMSA) scintigraphy, and its association with the identified urinary exosomal miRNAs was investigated. This prospective study enrolled 81 patients, comprising 33 males and 48 females, with a median age of 27 months (IQR: 8–82). Urinary exosomal miR-132-3p expression was significantly associated with higher reflux grade, bilateral reflux, and the presence of kidney scarring. Multivariate logistic analysis showed that urinary exosomal miR-132-3p (OR = 4.937, 95

Although toxicological studies suggest that synthetic phenolic antioxidants and their transformation products (SPAs/TPs) may disrupt thyroid function, epidemiological evidence and exposure safety thresholds remain limited. This study included 810 adults from Jiangsu Province, China, and measured serum concentrations of 12 SPAs, 3 TPs, and 7 thyroid function indicators (TFIs). Multiple linear regression (MLR) and restricted cubic spline (RCS) analyses were used to evaluate associations between individual SPAs/TPs and TFIs, whereas quantile g-computation (qgcomp) and Bayesian kernel machine regression (BKMR) were applied to assess the joint effects of mixed exposure. In addition, the Benchmark Dose Software (BMDS) was used to estimate the benchmark dose (BMD) and its lower confidence limit (BMDL) for serum SPAs/TPs, and to derive the corresponding reference doses (RfDs). The results showed widespread exposure to multiple SPAs/TPs among the study participants. Both individual and mixed exposure to SPAs/TPs were significantly associated with increased levels of free thyroxine (FT4) and total triiodothyronine (T3), as well as decreased levels of thyroid-stimulating hormone (TSH) and the T4/T3 ratio. Among the detected compounds, BHT-COOH (3,5-di-tert-butyl-4-hydroxybenzoic acid) and AO245 (triethylene glycol bis(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate) were the primary contributors to elevated FT4 and T3 levels. Under a benchmark response (BMR) of 5%, the estimated RfDs were 0.018 mg/kg/day for BHT-COOH and 0.181 mg/kg/day for AO245, and potential health risks may exist (HQc > 1). This study is the first to evaluate the effects of exposure to SPAs/TPs on thyroid homeostasis, providing a scientific basis for the formulation and improvement of targeted regulatory policies.

Foodborne Vibrio species commonly contaminate seafood and often co-occur, complicating rapid on-site detection. We developed a centrifugal microfluidic chip integrating one-pot RPA-CRISPR/Cas12a for simultaneous detection of four key species: V. parahaemolyticus, V. vulnificus, V. cholerae, and V. alginolyticus. In this system, target-specific RPA amplification generates amplicons that activate Cas12a-mediated trans-cleavage of fluorescent ssDNA reporters, producing target-dependent fluorescence signals for pathogen identification. The chip has eight units, each with four reaction chambers with lyophilized target-specific reagents, enabling a simple "DNA-in, result-out" workflow. Operating at 39 °C, the assay is completed within 60 min in a closed system to minimize contamination. It shows high specificity with no cross-reactivity. Limits of detection are 100 copies/μL for V. parahaemolyticus and V. vulnificus, and 101 copies/μL for V. cholerae and V. alginolyticus. Performance in spiked and real shrimp samples matched qPCR, with 100% sensitivity and specificity. The portable platform costs about $3.29 per test. This platform offers a practical approach for on-site multiplex screening of pathogenic Vibrio in seafood.

POEMS syndrome is a rare paraneoplastic disorder driven by clonal plasma cell proliferation and systemic inflammation, but existing prognostic models inadequately incorporate inflammation-related parameters. The neutrophil-to-lymphocyte ratio (NLR)—a simple, accessible marker of systemic inflammation and immune status—lacks systematic prognostic validation in POEMS syndrome. This single-center retrospective study enrolled 61 patients. The cohort was stratified into two eras (2010–2017 and 2018–2025) to assess temporal consistency. Receiver operating characteristic analysis was used to derive an exploratory NLR cut-off for overall survival. Kaplan–Meier curves and Cox proportional hazards regression were used to assess associations between NLR and progression-free survival (PFS), overall survival (OS), and independent prognostic significance. The effect modification by Li’s prognostic risk strata was explored using interaction and stratified analyses. Correlations were tested by Spearman’s coefficient between NLR and C-reactive protein (CRP), and AUCs were compared by DeLong’s test. ROC analysis showed moderate discrimination of baseline NLR for OS (AUC 0.736, 95

BACKGROUND:Endothelium-derived NO is an important vasodilator essential for maintaining vascular homeostasis. However, how eNOS (endothelial nitric oxide synthase) is regulated in hypertension conditions is not yet fully understood. In this study, we describe a critical role of the GLRA2 (α2 subunit of glycine receptor) in modulating eNOS signaling and blood pressure regulation. METHODS:Endothelial-specific Glra2-deficient mice and the adeno-associated viral-transfected mice were generated to assess the role of GLRA2 in hypertension models. Endothelium-dependent relaxation response and whole-cell patch clamp recording were determined. RESULTS:We first demonstrated selective expression of GLRA2 in arterial endothelial cells. Activation of GLRA2 by its ligand, glycine, effectively counteracts hypertension in a GLRA2-dependent manner. Our patient study indicated a negative correlation between plasma levels of glycine and blood pressure. Furthermore, we showed that endothelial GLRA2 regulates vasodilation by promoting NO production, rather than functioning solely as a chloride channel. Mechanistically, GLRA2 facilitates the phosphorylation of glycogen synthase kinase-3β at Ser9 (serine 9), which activates the AKT (protein kinase B)/eNOS signaling pathway in the endothelium, leading to increased NO release. CONCLUSIONS:This study discovers that a novel endothelial GLRA2 pathway holds significant potential for developing new strategies to control hypertension.

BackgroundThe synergistic effect of PM2.5 and house dust mite (HDM) in exacerbating allergic rhinitis (AR) is recognized, but the underlying molecular mechanisms remain unclear.ObjectiveThis study investigated whether PM2.5 aggravates HDM-induced AR and nasal epithelial barrier damage via the STING signaling pathway.MethodsThis research combined bioinformatics analysis of a human nasal transcriptome dataset with in vivo (BALB/c mouse model) and in vitro (Human Nasal Epithelial Cells, HNEpCs) experiments. Models were exposed to PM2.5 and HDM, alone or in combination. Rhinitis symptoms, epithelial barrier integrity, Th2 inflammation, and the STING/NF-κB pathway were assessed. The STING inhibitor H-151 was used for functional validation.ResultsBioinformatics analysis linked PM2.5 exposure to TNF/NF-κB signaling. In vivo and in vitro experiments consistently demonstrated that co-exposure to PM2.5 and HDM synergistically worsened nasal symptoms, Th2 responses (elevated IL-4, IL-5, IL-13, IgE), and impaired barrier function (downregulated E-cadherin and Claudin-1), while activating the STING/NF-κB pathway. Critically, H-151 treatment reversed these pathological changes.ConclusionPM2.5 disrupts the nasal epithelial barrier and synergizes with HDM to exacerbate allergic inflammation by activating the STING/NF-κB pathway. This study identifies STING as a potential therapeutic target for environment-aggravated allergic diseases.

Endothelial cells (ECs) are essential components of the vertebrate circulatory system; however, a comprehensive atlas characterizing how ECs acquire organ-specific transcriptomic heterogeneity has not been established. Here, we generated a time-series endothelial resource covering the entirety of mouse embryonic development, including 26 time points and 8 organs. Time-series multi-organ comparison revealed emergence timing and lineage trajectory of organotypic ECs together with organ-specific genes and pathways. Using these resources, we found that most ECs showed distinguishable organ specificity before late gestation. The organotypic EC-enriched genes were associated with vascular function in the organs. Human and mouse pulmonary ECs underwent an evolutionarily conserved transcriptional transition. Endothelial-specific knockout of Casz1, a pulmonary EC-enriched transcription factor, resulted in impaired vascular growth, disturbed pulmonary endothelial organotypic differentiation, and deficient epithelial-EC crosstalk. Our work provides a powerful endothelial resource that reveals fundamental principles of organ-specific EC differentiation and uncovers previously unknown molecular mechanisms governing lung-specific vascular development.

INTRODUCTION:Cyclophosphamide (CTX) is widely used in chemotherapy; however, its clinical application is frequently accompanied by gonadotoxic effects, which can result in impaired ovarian function and subsequent infertility in women. Consequently, effective strategies to mitigate chemotherapy-induced ovarian injury remain an important unmet need. Interleukin-35 (IL-35), a recently identified member of the IL-12 cytokine family, has been implicated in immune regulation and the maintenance of immune homeostasis. In parallel, accumulating evidence indicates that ovarian damage involves multiple forms of regulated cell death rather than a single apoptotic pathway. PANoptosis, an integrated cell-death program encompassing pyroptosis, necroptosis, and apoptosis, has recently emerged as a key mechanism in tissue injury. To date, whether IL-35 participates in CTX-induced ovarian injury and whether it modulates PANoptosisrelated pathways has not been clearly elucidated. MATERIALS AND METHODS:Female C57BL/6 mice were randomly divided into four groups: control, CTX treatment, IL-35 treatment, and combined CTX + IL-35 treatment. Histopathological alterations in ovarian tissue were assessed using hematoxylin and eosin staining, whereas ELISA, qRT-PCR, immunohistochemistry, and western blot assays were subsequently conducted to investigate potential molecular mechanisms. RESULTS:IL-35 showed a protective effect against CTX-induced ovarian injury. Serum FSH levels were reduced. Serum E2 and AMH levels were increased. Ovarian histopathological structure was improved. CTX treatment increased oxidative stress markers. These markers included ROS, SOD, and MDA. CTX treatment increased apoptosis markers (Bax and Bcl2). CTX treatment increased pyroptosis markers (NLRP3 and IL-1β). CTX treatment increased necroptosis markers (p-MLK and p-RIPK1). IL-35 pretreatment reduced all listed molecular changes. Further analysis showed enhanced activation of the ovarian Nrf2/HO-1 signaling pathway after IL-35 pretreatment during CTX exposure. DISCUSSION:IL-35 preserves ovarian reserve during CTX challenge by activating Nrf2/HO-1 to restore redox balance, thereby coordinately inhibiting pyroptosis, necroptosis, and apoptosis-key drivers of chemotherapy-induced follicular depletion. CONCLUSION:IL-35 reduced CTX-induced ovarian injury. This effect occurs through the regulation of oxidative stress and PANoptosis. These findings indicate the therapeutic potential of IL- 35 for ovarian injury caused by CTX.

Background: Observational studies have reported that arm fat, left leg fat, and trunk fat masses have different effects on polycystic ovarian syndrome (PCOS). However, the causal relationship between them remains unknown. Materials and Methods: A two-sample Mendelian randomization (MR) study was conducted by utilizing pooled data from the largest Genome-Wide Association Study (GWAS). Random effect inverse variance weighted (IVW) method, weighted median (WM), and MR-Egger regression analysis were the main statistical methods utilized. Finally, a sensitivity assessment was conducted. Cochran’s Q test was used to analyze heterogeneity, whereas MR-Egger regression (intercept term) was used to analyze horizontal pleiotropy. The leave-one-out analysis was performed to assess if MR estimates were impacted by a single nucleotide polymorphism (SNP) exhibiting significant horizontal pleiotropy. Results: This study discovered a significant positive correlation between left leg fat mass, arm fat mass, and trunk fat mass and genetic factors of PCOS (odds ratio (OR): 4.452, confidence interval (CI): 2.740−7.232, p < 0.001, OR: 3.321, CI: 2.248−4.907, p < 0.001, and OR: 2.518, CI: 1.722−3.682, p < 0.001, respectively). Conclusion: This study indicates that arm fat, left leg fat, and trunk fat masses may be genetically correlated with PCOS.

Monocyte-macrophage transition is dysregulated in inflammatory bowel disease. While polycomb repressive complexes are crucial for maintaining cellular identity, their specific roles in colitis are poorly defined. Here, we show that Ring finger protein 2, a core catalytic subunit of polycomb repressive complex 1, regulates the monocyte-macrophage transition during colitis. It is highly expressed in the immature colon and circulating monocytes during ulcerative colitis. And mice with myeloid-specific deficiency exhibited attenuated experimental colitis, restored monocyte/macrophage balance, and improved anti-tumor necrosis factor alpha efficacy. Mechanistically, Ring finger protein 2 represses Runt-related transcription factor 3 expression via histone H2A lysine 119 monoubiquitination. This disrupts the inhibition of the recombination signal-binding protein for the immunoglobulin kappa J region, the central activator of the Notch pathway, thereby exacerbating inflammation. Silencing of the axis markedly inhibited proinflammatory responses, regulating monocyte-macrophage transition. These findings reveal that Ring finger protein 2 disrupts the monocyte-macrophage transition during colitis, offering insights into colitis treatments.

Mitochondrial dysfunction plays a key role in the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). As is known to play a key role in mitochondria, ECSIT, in relation to oxidized mitochondrial DNA is still unclear. This study examines mitochondrial ECSIT expression in MASH mouse models. Mitochondria-targeted ECSIT transgenic (ECSITMTG) mice and wild-type (WT) controls are fed a high-fat, high-cholesterol (HFHC) diet for 16 weeks or a methionine- and choline-deficient (MCD) diet for 8 weeks. Results demonstrate that mitochondrial ECSIT overexpression alleviates diet-induced MASH phenotypes. Mechanistically, we demonstrate that mitochondrial ECSIT promotes the localization of the deubiquitinase OTUD3 to mitochondria. OTUD3 then stabilizes SIRT3 via deubiquitination, thereby inhibiting mtDNA oxidation and alleviating steatosis-induced metabolic disorders. Overall, these findings indicate that mitochondrial ECSIT protects against MASH progression by stabilizing SIRT3, suggesting its potential as a therapeutic target.

Doxorubicin (DOX), a widely used chemotherapeutic agent, induces severe ovarian damage resulting in premature ovarian insufficiency and reduced fertility. In the present study, through transcriptome sequencing and immune cell infiltration analysis, we demonstrated that DOX significantly upregulates ovarian CCL8 expression, thereby activating the CCL8/CCR5 axis to promote the recruitment and polarization of proinflammatory M1 macrophages. Mechanistically, CCL8 exacerbates local inflammation through NF-κB signaling (evidenced by p65 phosphorylation and IκBα degradation), initiating granulosa cell apoptosis and follicular atresia. The CCL8-specific inhibitor Bindarit effectively mitigated this pathological cascade by (1) reducing macrophage infiltration by 90.9% ( P < 0.01), (2) inhibiting NF-κB activation (99.3% decrease in p65 nuclear translocation, P < 0.001), and (3) downregulating proinflammatory cytokines (reduction in TNF-α/IL-1β expression: 80–90%, P < 0.001). Notably, Bindarit treatment restored 54.5% of fertility capacity ( P < 0.01) in DOX-treated mice (which showed 84.1% fertility loss). These findings illuminate the crucial role of the CCL8/NF-κB axis in DOX-induced ovarian toxicity and propose a novel therapeutic strategy for fertility preservation. Bindarit could serve as a promising CCL8-targeted agent with substantial clinical potential.

Fatty acid (FA) overload imposes substantial stress on hypothalamic neurons, whilst whether cortical input could improve metabolic resilience of hypothalamic neurons remains poorly understood. Here, we reconstructed human cortical-hypothalamic assembloids (CO-HTO assembloids) to investigate how cortical input modulates hypothalamic responses to FA. Our results revealed that FA could impair neuronal survival, α-MSH secretion, and electrophysiological activity in hypothalamic organoids (HTOs). Remarkably, fusion with cortical organoids (COs) could prevent FA-induced apoptosis and functional defects, preserve mitochondrial respiration, and reduce lipid accumulation in HTOs. Also, transcriptomic and functional analyses revealed that cortical input could activate PGC1α-dependent mitochondrial biogenesis. Furthermore, pharmacological PGC1α activation or glutamate treatment rescued the FA-induced defects in HTOs. Collectively, our findings uncovered a cortico-hypothalamic regulatory axis and found glutamate-driven PGC1α activation might maintain hypothalamic neuronal stability and improve resilience to metabolic stress. Our CO-HTO assembloids provided a promising platform to investigate complex inter-regional communications and related neurological and metabolic disorders.

Objective:Chromosomal instability (CIN) drives genomic structural variants (such as amplifications and deletions) and promotes tumor progression. Long noncoding RNAs are known to participate in key biological processes and CIN regulation. Our previous study demonstrated that the highly expressed lncTRDMT1-5 serves as a novel prognostic biomarker in breast cancer; however, its underlying mechanisms require further investigation. Methods:LncTRDMT1-5 expression was knocked down in MDA-MB-231 cells, followed by chromosomal microarray analysis (CMA). Expression levels of lncTRDMT1-5 were examined in breast cancer cells and tissues via RT-PCR. Chromatin immunoprecipitation was used to detect H3K27 acetylation in the promoter region. RNA pull-down was performed to identified interactions with the MSRB3 protein. Cell proliferation was evaluated by EdU assay, DNA damage was assessed by γH2AX immunofluorescence, and cell cycle distribution was analyzed by flow cytometry. EMT-related protein expression and cell cycle regulators were examined by western blotting. Results:LncTRDMT1-5 was significantly upregulated in breast cancer cells and tissues, with H3K27 acetylation detected in its promoter. Downregulation of lncTRDMT1-5 induced CNVs across different chromosomes. Overexpression of lncTRDMT1-5 promoted cell proliferation, DNA damage, and EMT-related protein expression. RNA pulldown confirmed the relationship between lncTRDMT1-5 and MSRB3 protein. Mechanistically, lncTRDMT1-5 regulated cell cycle arrest by inhibiting p53 and inducing the expression of cell-division cycle protein 20 homologue (CDC20). Conclusion:Overexpression of lncTRDMT1-5 in breast cancer induces CIN and tumor progression by promoting EMT process and increasing MSRB3, p53 and CDC20 protein expression. Targeting this molecular pathway may offer novel therapeutic strategies and improve prognostic evaluations.

BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis. DDB1 and CUL4 associated factor 13 (DCAF13) has been implicated in tumor progression, but its clinical relevance and biological function in PDAC remain unclear. METHODS:Public databases (GEPIA2 and Kaplan-Meier Plotter) were used to analyze DCAF13 expression and its prognostic value in PDAC. Tumor and paired adjacent tissues from 90 PDAC patients were examined by immunohistochemistry to assess DCAF13 protein expression and its association with clinicopathological features and survival. DCAF13 expression in HPDE6-C7, AsPC-1 and MiaPaCa-2 cells was detected by qRT-PCR and Western blotting. Gain- and loss-of-function models were established to evaluate the effects of DCAF13 on cell migration, invasion and apoptosis using wound healing, Transwell and flow cytometry assays. Changes in p53-related signaling proteins were examined by Western blot. RESULTS:Bioinformatic analyses revealed significantly elevated DCAF13 expression in PDAC and its association with shorter overall and disease-free survival. Clinically, DCAF13 protein was overexpressed in PDAC tissues and correlated with tumor differentiation (P = 0.006). In PDAC cell lines, DCAF13 knockdown suppressed migration and invasion while promoting apoptosis in vitro, whereas DCAF13 overexpression exerted the opposite effects. In TP53-mutant PDAC cells, DCAF13 knockdown was associated with increased expression of p53-related proteins, including p53 and its downstream targets p21, BAX and FAS, suggesting a potential association between DCAF13 and altered p53-related signaling in this cellular context. CONCLUSIONS:DCAF13 is overexpressed in PDAC and associated with poor prognosis. DCAF13 may promote malignant phenotypes in vitro and alter p53-related signaling in TP53-mutant PDAC cells. These findings suggest that DCAF13 may have potential value as a prognostic biomarker and exploratory therapeutic candidate for PDAC, although further validation in WT-p53 and in vivo models is still required.

Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder, but whether intrinsic capacity (IC), a multidomain measure of functional reserve, is associated with incident IBD remains unclear. We analysed 427,489 UK Biobank participants free of IBD at baseline and examined associations of baseline IC deficit burden with incident IBD, Crohn’s disease (CD), and ulcerative colitis (UC), as well as joint effects with polygenic risk scores (PRS). During a median follow-up of 13.73 years (interquartile range [IQR], 12.99–14.44 years), 3,719 participants developed IBD. Compared with participants with no IC deficits, those with 2, 3, and > = 4 deficits had progressively higher risks of incident IBD, and incidence rates increased from 0.556 to 1.067 per 1,000 person-years across IC categories. Associations were stronger for CD than for UC; participants with > = 4 deficits had hazard ratios of 2.614 for CD and 1.338 for UC. IC deficit burden provided complementary risk information across PRS strata, with the highest absolute risks observed among individuals with high PRS. These findings suggest that reduced IC is independently associated with increased IBD risk and may provide complementary information for risk stratification.

Objective The aim of this study was to investigate the effects of SEPT9 on proliferation, migration, and apoptosis in endometriotic stromal cells and to explore the underlying mechanisms. Methods Immunohistochemistry and western blotting revealed that SEPT9 expression was significantly elevated in ectopic and eutopic endometrial tissues from patients with endometriosis compared with normal endometrial tissues (p<0.05). Using immortalized human eutopic and ectopic endometrial stromal cells, genetic recombination was applied to overexpress SEPT9 in eutopic cells and knock down SEPT9 in ectopic cells. Results Transwell migration, EdU proliferation, and flow cytometry assays showed that SEPT9 overexpression enhanced cell proliferation and migration, whereas SEPT9 silencing reduced these behaviors and increased apoptosis. Pathway analyses identified the PI3K/AKT signaling pathway as a downstream target of SEPT9. Consistently, western blotting and qRT-PCR following SEPT9 knockdown confirmed decreased expression of PI3K/AKT-related proteins and genes. Conclusion In conclusion, silencing SEPT9 inhibited proliferation and migration and promoted apoptosis in endometriotic stromal cells, potentially through suppression of the PI3K/AKT signaling pathway.