Search Results (291)

Background/Objectives: Triple-negative breast cancer (TNBC) is frequently characterized by notably elevated Ki-67 expression, a hallmark of uncontrolled rapid cell-cycle progression. However, the underlying mechanisms remain unclear, leading to limited therapeutic options. Methods: In this study, hub gene was identified through integrated bioinformatic analysis of public datasets (TCGA-BRCA and METABRIC). Subsequent functional validation was performed both in vitro and in vivo using siRNA-mediated knockdown and small-molecule inhibitors. Phenotypic effects—including cell viability, cell cycle distribution, DNA synthesis, and clonogenic survival—were comprehensively assessed using MTT assays, flow cytometry, EdU, and colony formation assays. Protein-level changes were confirmed by Western blotting and immunohistochemistry (IHC). To dissect the transcriptional regulation of the key hub gene TTK, we first predicted potential upstream transcription factors using the JASPAR database; binding specificity was then validated through in silico motif analysis, luciferase reporter assays, and chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR). Results: The mitotic kinase TTK is significantly overexpressed in TNBC compared with non-TNBC breast cancers. Notably, TTK overexpression exhibited a strong positive correlation with elevated Ki-67 indices and reduced overall survival in TNBC patients. Functional validation demonstrated that pharmacological or genetic inhibition of TTK effectively induced G2/M cell-cycle arrest and potently suppressed TNBC proliferation in both in vitro cell cultures and in vivo xenograft models. Mechanistically, TTK overexpression stems from enhanced transcriptional initiation driven by the transcription factor NFYA binding to the CCAAT box in the TTK promoter—an interaction newly identified here. Concurrently, TTK blockade disrupted spindle assembly checkpoint (SAC) signaling via BUB1B/MAD1L1 downregulation, triggering mitotic arrest and catastrophe. Conclusions: Collectively, these findings establish TTK as a key cell-cycle regulator driving TNBC proliferation. More importantly, targeting mitotic control through TTK inhibition represents an efficient strategy to impede the aberrantly fast cell cycle progression in TNBC. Full article

Realizing high-quality-factor (high-Q) plasmonic resonances in the visible regime is critical for enhancing light-matter interactions and advancing biochemical sensing. However, traditional localized surface plasmon resonances (LSPRs) typically suffer from broad spectral linewidths due to severe radiative damping. In this work, we propose a simple two-dimensional symmetric gold nanohole-array metasurface that supports a symmetry-protected bound state in the continuum (SP-BIC) at normal incidence. By introducing extrinsic symmetry breaking via oblique incidence, this non-radiative dark state is successfully transformed into an observable high-Q quasi-BIC Fano resonance. Cartesian multipole decomposition reveals that this sharp mode ($\lambda \approx 688$ nm) is predominantly driven by a tightly confined Magnetic Dipole (MD) excitation, which drastically suppresses radiative leakage compared to the highly damped Electric Dipole (ED)-dominated LSPR. Consequently, the quasi-BIC mode exhibits an ultra-narrow spectral linewidth ($\mathrm{FWHM}\approx 17.4$ nm). While its bulk sensitivity ($236.9$ nm/RIU) is slightly lower than that of the LSPR mode, the exceptionally sharp resonance yields a remarkably low Limit of Detection (LOD) of $7.35\times {10}^{-3}$ RIU, achieving a nearly five-fold improvement over the traditional LSPR. Furthermore, the quasi-BIC mode maintains an outstanding Figure of Merit (FOM up to ∼19.7 ${\mathrm{RIU}}^{-1}$) across the entire sensing range. By eliminating the need for complex asymmetric nanofabrication, this robust angle-tuned design strategy provides a highly promising platform for the development of high-resolution, low-cost optical biosensors. Full article

Breast cancer (BRCA) is the most common cancer worldwide, with an incidence exceeding that of lung cancer. Protein lactylation, a newly identified post-translational modification involving the binding of lactic acid to lysine residues, plays an important role in BRCA. However, its role in BRCA progression remains largely unexplored. This study aims to identify and characterize the lactylation-related genes involved in BRCA biology. Transcriptomic and clinical data of BRCA and normal breast tissues were obtained from TCGA and GEO. Lactylation-related genes were curated from literature and intersected with BRCA datasets to identify candidates. A prognostic risk model was constructed using LASSO and Cox regression. Functional enrichment was performed using KEGG, GSVA, and GSEA. Immune correlations were evaluated by ESTIMATE, CIBERSORT. Single-cell RNA-seq data were integrated to assess gene expression heterogeneity across tumor and immune compartments. In vitro, MDA-MB-231 cells were treated with sodium L-lactate and lactylation-inducing agents, and gene expression was validated by Western blot and RT-qPCR, while EdU and wound healing assays evaluated proliferation and migration. We identified six hub genes associated with the immune microenvironment. Notably, S100A4 is significantly underexpressed, suggesting their potential regulatory roles in BRCA. Further analysis demonstrated that lactylation-related genes are closely linked to immune regulation in BRCA, indicating a possible crosstalk between metabolic modification and tumor immunity. Additionally, we found that lactylation significantly influences gene expression patterns and immune infiltration in BRCA. Importantly, lactic acid ions were shown to upregulate lactylation levels in BRCA cells, underscoring the functional impact of metabolic signals on post-translational modifications in tumorigenesis. Our findings indicate a potential mechanism wherein lactylation affects BRCA progression via lactic acid-driven regulation of the immune microenvironment; they also highlight the possible involvement of S100A4 in this process and offer new insights that could contribute to the diagnosis and treatment of BRCA. Full article

Fly ash is an effective supplementary cementitious material for reducing clinker consumption and carbon emissions, but its low early reactivity often results in delayed hydration and insufficient early-age strength. This study investigated the age-dependent role of graphene oxide (GO) in fly ash-blended cementitious materials by combining compressive strength testing with X-ray diffraction (XRD), thermogravimetric analysis (TG-DTG), ²⁹Si magic-angle spinning nuclear magnetic resonance (²⁹Si MAS NMR), and scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS). Fly ash replacement levels of 10%, 20%, and 30% were considered, and 0.07% GO was introduced to evaluate its effect at 3, 7, and 28 days. The results showed that fly ash reduced the 3-day compressive strength, whereas the strength differences became much smaller at 28 days. GO enhanced the compressive strength of all fly ash-blended mixtures. XRD and TG-DTG results showed that GO refined Ca(OH)₂ crystallization and reduced the retained CH content, indicating more effective CH utilization during hydration and pozzolanic reaction. At 28 days, the incorporation of 0.07% GO increased the compressive strength of the 30% fly ash mixture from 47.38 MPa to 56.58 MPa, while reducing the total CH content from 14.20% to 12.89%, indicating enhanced CH utilization and gel development. ²⁹Si MAS NMR further demonstrated that GO promoted a more mature and polymerized silicate gel structure, as evidenced by lower Q⁰ fractions, higher mean chain length, and higher proportions of more polymerized silicate species. SEM-EDS observations confirmed that GO led to a denser matrix, less dominant coarse CH, and lower Ca/Si and Ca/(Si + Al) ratios. Overall, GO improved the mechanical performance of fly ash-blended cementitious materials through coupled regulation of hydration products, silicate gel polymerization, and matrix densification. Full article

Background/Objectives: This study was conducted to determine the validity and reliability of the Eating-Related Eco-Concern (EREC) in young Turkish adults and to evaluate the effect of ecological concerns on disordered eating characteristics, with a view to comparing these effects with the risk of eating disorders. Methods: The study included 600 young adults (138 males and 462 females) aged 18 to 35. Using face-to-face administration, the Eating Disorder Examination Questionnaire (EDE-Q-13) Short Form to assess eating disorder-related psychopathology and the EREC Scale to assess eating behaviors related to eco-concern were administered, and Turkish validity and reliability were examined. Results: The Kaiser–Meyer–Olkin (KMO) was 0.801, signifying acceptable sample adequacy, while Bartlett’s test of sphericity was significant (χ² = 636.159, p < 0.001). All item factor loadings ranged from 0.582 to 0.767 and were statistically significant (p < 0.001). The scale’s Cronbach’s alpha was 0.854. Test–retest reliability was good, with an infraclass correlation coefficient (ICC) of 0.811 95% CI. The analysis revealed that the single-factor model demonstrated an acceptable fit to the data (χ²/df = 2.84, CFI = 0.976). There was no statistically significant correlation between EREC and the total EDE-Q-13 score (p = 0.064). On the other hand, the total EDE-Q-13 score was identified as a significant negative predictor of EREC scores (β = −2.648, p = 0.028). Conclusions: All item factors of the Turkish adaptation of the scale exhibit a structure that is quite consistent with the original scale. The 10-question version of EREC can be used with young adults in Türkiye. In this study, although ecological anxiety was associated with eating restraint or purging, it was not found to be generally associated with eating disorders. Full article

Background: The Child and Adolescent Eating Disorder Examination Questionnaire (ChEDE-Q) is a widely used self-report screening instrument for assessing eating disorder psychopathology in young people. Evidence on the psychometric properties of the Polish-language version remains limited. This pilot study evaluated the internal consistency, dimensional structure, and BMI-related convergent validity of the Polish ChE-DE-Q in a regional youth sample. Methods: A cross-sectional design was used, including 200 participants aged 10–18 years. Item characteristics and data quality were examined. Internal consistency was assessed using Cronbach’s alpha and McDonald’s omega. Dimensional structure was evaluated with exploratory factor analysis (EFA) based on a polychoric correlation matrix and confirmatory factor analysis (CFA) comparing one-factor, four-factor, and bifactor models. Convergent validity was examined using Spearman’s rank correlations with BMI and linear regression analyses with BMI z-scores. Results: The global score showed high internal consistency (α = 0.898; ω = 0.900). Subscale reliability ranged from acceptable to high. EFA supported a multidimensional solution. In CFA, the bifactor model showed the best fit among the tested alternatives (CFI = 0.742; TLI = 0.681; RMSEA = 0.122; SRMR = 0.084), but none of the tested models achieved fully satisfactory absolute fit. The global score correlated positively with BMI (rho = 0.282; p < 0.001) and was significantly associated with BMI z-score in regression analysis (B = 0.334; p < 0.001). Conclusions: The Polish ChEDE-Q global score demonstrated strong internal consistency and preliminary BMI-related convergent validity. The findings provide initial support for a general factor and for using the global score in screening-oriented research; however, the pilot character of the study and the suboptimal absolute fit indices indicate that further validation in larger and more heterogeneous samples is required. Full article

The performance improvement of mechanical components often relies on heat treatment processes, but these processes inevitably result in oxidation burn-off. The repeated formation and spallation of Fe₂O₃ rich oxide scales lead to substantial iron depletion and surface deterioration. Consequently, environmentally sustainable and economically viable protective coatings are required to suppress oxidation induced burn off. In this work, a TiO₂-MgAl₂O₄ composite coating was synthesized from magnesium slag and applied to Q235 carbon steel to enhance its performance during prolonged high temperature heat treatment. Oxidation tests conducted at 900 °C for 60 min demonstrated that the coating markedly improved the oxidation resistance of carbon steel, with an enhancement of approximately 87% relative to the uncoated specimens. To elucidate the protective mechanism, SEM-EDS, XRD, TG-DSC, and XPS analyses were employed. Based on Wagner Theory, the formation of interfacial phases such as Mg_7.92Al_15.31Fe_0.66O₃₂, which effectively impeded oxygen ion diffusion and thereby enhanced the oxidation resistance during high-temperature exposure. Furthermore, the synergistic effect of aluminum-, magnesium-, and titanium-containing compounds in the coating contributed to suppressing the diffusion of oxygen and iron ions, thus further improving the protective performance. This study provides a systematic theoretical foundation and practical guidance for addressing material loss during high-temperature processing of mechanical components, as well as for promoting the resource utilization of magnesium slag. Full article

This study aimed to examine the differences in self-compassion (SC) subcomponents between anorexia nervosa (AN) subtypes, the restricting type (ANR) and binge-eating/purging type (ANBP), with a focus on perceived isolation and self-judgment. This retrospective exploratory study included 40 patients with AN at a Japanese tertiary hospital. The participants completed the Self-Compassion Scale, Patient Health Questionnaire-9, and Eating Disorder Examination Questionnaire. Between-group comparisons were conducted using t-tests, and logistic regression was used to examine associations with the AN subtype. Compared with the ANR group, the ANBP group was older at the time of assessment, had a longer illness duration, and showed significantly more depressive symptoms, more severe eating pathologies, and lower SC scores. Specifically, patients with ANBP had significantly higher scores on the negative SCS subscales of self-judgment and isolation, indicating greater self-criticism and perceived isolation. In logistic regression analyses adjusting for the EDE-Q mean score, higher isolation scores were significantly associated with the ANBP subtype (odds ratio = 3.28, 95% confidence interval: 1.37–9.63, p = 0.01). In this exploratory sample, perceived isolation was more prominent in ANBP and may reflect affective and interpersonal difficulties related to this subtype. These findings should be interpreted as hypothesis-generating and warrant replication in larger (ideally multi-site and longitudinal) samples. If replicated, targeting these self-compassion dimensions may inform the development of subtype-sensitive interventions. Full article

Background: Fibromyalgia (FM) and eating disorders (ED) represent distinct clinical entities traditionally managed within separate medical specialties, yet emerging evidence suggests significant comorbidity and potential shared pathophysiological mechanisms. Both conditions disproportionately affect women, involve complex multifactorial etiologies and substantially impair quality of life. Despite documented clinical overlaps, the mechanistic connections linking these conditions remain poorly characterized, and integrated treatment approaches are lacking. Objective: This narrative review examines the role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway dysfunction as a unifying molecular mechanism connecting fibromyalgia and eating disorders, with emphasis on implications for integrated rehabilitation strategies. Methods: We synthesized current evidence on oxidative stress pathophysiology in fibromyalgia and eating disorders, focusing on Nrf2-Keap1 pathway function, clinical comorbidity patterns and rehabilitation interventions targeting antioxidant defense mechanisms. In PubMed, representative search strings included “(fibromyalgia [MeSH] OR fibromyalgia [Title/Abstract]) AND (“eating disorders” [MeSH] OR “anorexia nervosa” [MeSH] OR “bulimia nervosa” [MeSH])” and “fibromyalgia AND (“oxidative stress” OR Nrf2 OR “redox”)”. Articles in English published through December 2025 were considered, with additional records identified by manually screening reference lists. Results: Fibromyalgia patients exhibit elevated oxidative stress markers, impaired antioxidant enzyme function and compromised Nrf2 activity correlating with disease severity, with studies reporting approximately 30–50% reductions in coenzyme Q10 levels compared with healthy controls. Similarly, eating disorders demonstrate mitochondrial dysfunction and oxidative stress dysregulation, though patterns differ across eating disorder phenotypes. Nrf2 serves as the master regulator of cellular antioxidant defense, coordinating expression of over 500 genes involved in detoxification, cytoprotection, inflammation modulation and metabolic regulation. Evidence suggests Nrf2 activity is regulated by energy balance, potentially linking nutritional status with cellular stress responses. Rehabilitation interventions, including graduated exercise and nutritional optimization with Nrf2-activating foods (cruciferous vegetables, polyphenols, omega-3 fatty acids), offer mechanism-based therapeutic approaches through hormetic Nrf2 activation and direct Keap1 modification. Conclusions: Multidisciplinary rehabilitation programs integrating physical therapy, exercise prescription and nutritional strategies targeting Nrf2 activation offer evidence-based, mechanism-driven approaches to address shared oxidative stress pathophysiology. Nrf2 pathway dysfunction represents a promising and biologically plausible molecular target that may help to unify our understanding of fibromyalgia and eating disorders pending confirmation from prospective clinical studies in comorbid populations. Future research should prioritize prospective clinical trials testing Nrf2-targeted interventions in comorbid populations and collaborative patient-centered care models. Full article

Background: Eating disorders (EDs) frequently co-occur with trauma-related symptoms and elevated autistic traits (ATs), both of which contribute to clinical complexity. Social camouflaging, strategies used to mask or compensate for ATs, has been increasingly described in ED populations, yet its relationship with trauma-related symptoms remains poorly understood. This study aimed to examine the association between social camouflaging and post-traumatic stress symptoms in individuals with EDs and to evaluate whether trauma-related symptomatology is associated with camouflaging behaviors. Methods: A total of 67 ED patients were assessed using the Adult Autism Subthreshold Spectrum, the Trauma and Loss Spectrum—Self Report (TALS-SR), the Camouflaging Autistic Traits questionnaire (CAT-Q), and the Eating Disorder Inventory (EDI-2). Participants were divided into high-trauma-symptoms (HTS) (N = 36, 53.7%) and low-trauma-symptoms (LTS) (N = 31; 46.3%) groups based on TALS-SR criteria. Results: The sample was predominantly female (92.5%), and gender distribution differed between groups, which may represent a potential confounding factor and limits the generalizability of the findings. The HTS group reported significantly higher TALS-SR, EDI-2, CAT-Q, and AdAS Spectrum scores, although for the latter the p-value was barely significant (p = 0.046). No differences emerged in the distribution of ED diagnoses between groups. CAT-Q scores were significantly positively correlated with TALS-SR total scores and with domains related to reaction to losses, maladaptive coping, avoidance/numbing, and personal vulnerability. Regression analyses showed that overall trauma-related symptoms were significantly associated with greater camouflaging; however, the proportion of explained variance was modest, suggesting that trauma-related symptoms represent only one of multiple factors linked to camouflaging. Conclusions: Among individuals with EDs, higher trauma-related symptomatology is linked to greater use of social camouflaging strategies. These findings suggest that camouflaging may represent a transdiagnostic correlate connecting neurodevelopmental vulnerability and trauma responses within ED populations, underscoring the importance of integrated assessment and trauma-informed care. Full article

Background/Objectives: Food insecurity (FI) is associated with adverse physical and mental health outcomes and poses unique challenges for individuals with celiac disease (CD), who must adhere to a lifelong, strict gluten-free diet (GFD) as their sole treatment. Gluten-free foods are often more expensive and less accessible, potentially exacerbating dietary burden and symptom severity. This study aimed to examine associations between food insecurity and gastrointestinal symptoms, dietary burden, disordered eating symptoms, and mental health outcomes in adults with CD. Methods: Participants were 397 adults with CD who completed a routine pre-visit screener at a tertiary celiac disease clinic in the southeastern United States. Food insecurity was assessed using the Hunger Vital Signs. Measures included gastrointestinal symptoms (GSRS), impact of following a gluten-free diet (IGFDQ), avoidant/restrictive eating (NIAS), eating disorder psychopathology (EDE-Q7), anxiety (GAD-2), and depression (PHQ-2). Group comparisons between food-secure and participants screening positive for food insecurity (high-risk of FI) were conducted using independent t-tests or Mann–Whitney U tests as appropriate. Missing data were handled using multiple imputations. Results: A total of 15.6% of participants were at high risk of FI. Compared to food-secure individuals, participants at high-risk of FI reported significantly greater gastrointestinal symptom severity, including bloating, constipation, diarrhea, and overall symptom burden. Participants at high risk of FI also reported significantly greater perceived burden of adhering to a gluten-free diet. Additionally, higher levels of avoidant/restrictive eating symptoms and shape/weight overvaluation were observed among high-risk FI individuals, though group differences in anxiety and depression symptoms were not statistically significant. Conclusions: FI is associated with greater gastrointestinal symptom burden and increased difficulty adhering to a gluten-free diet among adults with celiac disease. These findings highlight risk of FI as a clinically relevant barrier to effective disease management and underscore the importance of routine screening and targeted support for high-risk FI individuals with CD. Full article

Beta-2-microglobulin (B2M) is a key component protein in the processing and presentation of major histocompatibility complex (MHC)-I antigens and plays an important role in the immune system regulation. Previous studies have shown that B2M is significantly overexpressed in the intestinal tissues of sheep that are resistant to E. coli F17b infection (defined by milder clinical symptoms post-challenge) compared to those that are susceptible (exhibiting severe diarrhea). Based on this finding, this study aimed to investigate whether B2M influences the adhesion of E. coli F17b to sheep intestinal epithelial cells (IECs) and to assess its role in regulating IEC proliferation and migration. We tested this by overexpressing and knocking down B2M in IECs, and then measured bacterial adhesion through colony counts and fimbrial gene expression (RT-qPCR). Moreover, cell health was assessed using proliferation (CCK-8 and EdU) and migration (scratch) assays. The results showed that upregulation of B2M expression inhibited E. coli F17b adhesion and promoted IEC proliferation and migration. Silencing B2M increased bacterial adhesion and impaired cell function. In summary, B2M helps protect sheep IECs from E. coli F17b by strengthening the epithelial barrier through improved cell growth, proliferation, and migration. These findings elucidate part of the host defense mechanism against E. coli F17b, providing a basis for further research. Full article

Objective: Rare-earth elements are extensively employed across diverse industrial sectors, increasingly raising concerns about their potential health hazards in both occupational and environmental contexts. Samarium oxide (Sm₂O₃), a routinely processed rare-earth product, reproducibly precipitates pulmonary fibrosis in experimental models, yet the molecular circuitry that transduces its fibrogenic signal remains almost entirely unmapped. This study aims to elucidate the role of miR-214-3p in Sm₂O₃-induced pulmonary fibrosis and to investigate its regulatory mechanism at the molecular level. Methods: A murine model of pulmonary fibrosis was established via intratracheal instillation of Sm₂O₃, and histopathological changes were assessed using hematoxylin and eosin (H&E) and Masson’s trichrome staining. RNA sequencing was performed on lung tissues to identify differentially expressed mRNAs. Leveraging our previously generated miRNA landscape of Sm₂O₃-exposed lungs, we subjected the dataset to Gene Ontology and KEGG enrichment analyses, which convergently identified miR-214-3p as the top-ranking candidate regulator of the fibrogenic MAPK axis. The direct targeting of MAP2K3 by miR-214-3p was validated using a dual-luciferase reporter assay. Expression levels of fibrotic markers (α-SMA, Collagen I) and key components of the MAPK signaling pathway (MAP2K3, p-MAPK14, MST1) were quantified in both in vivo and in vitro models using qRT-PCR and Western blotting. Gain- and loss-of-function studies, complemented by rescue assays, were performed in human embryonic lung fibroblasts (HELFs) via transient transfection of miR-214-3p mimics, inhibitors, or MAP2K3-overexpression plasmids. Cell proliferation was evaluated using the EdU assay, and TGF-β1 secretion was measured by ELISA. Results: Sm₂O₃ exposure induced significant pulmonary fibrosis in mice, accompanied by marked downregulation of miR-214-3p and upregulation of MAP2K3 in lung tissues. Overexpression of miR-214-3p or silencing of MAP2K3 effectively suppressed Sm₂O₃-induced fibroblast activation, including reduced cell proliferation, decreased expression of α-SMA and Collagen I, and inhibition of p38 MAPK phosphorylation. Notably, ectopic overexpression of MAP2K3 reversed the protective effects conferred by miR-214-3p, confirming a functional rescue. Conclusions: miR-214-3p directly silences MAP2K3, thereby blunting p38 MAPK-driven fibrogenesis after Sm₂O₃ exposure. Our data unveil a miR-214-3p–MAP2K3–p38 MAPK axis that constitutes a readily druggable target for rare-earth-element-induced pulmonary fibrosis. Full article

Eating disorders (EDs) are complex conditions that can significantly affect health and productivity, yet their assessment in occupational settings remains underexplored. This study aimed to evaluate the psychometric properties of the Italian version of the Eating Disorder Examination Questionnaire—Short Form (EDE-QS) among 1912 workers undergoing health surveillance. Using an Item Response Theory framework, we tested dimensionality, reliability, and measurement invariance across gender, applying a graded response model to assess item discrimination and threshold parameters. Results supported an approximate unidimensional structure with excellent internal consistency (ω ≈ 0.95) and strong indices of factor score determinacy and construct replicability. Measurement invariance analyses indicated configural and metric invariance but not full scalar invariance, due to differential item functioning in a subset of items. Latent mean differences were small, with women scoring slightly higher than men, and associations with psychological, occupational, and health-related variables did not differ by gender. These findings indicate that the Italian EDE-QS shows promising structural validity as a brief measure of ED symptomatology in occupational samples in workplace contexts. However, gender-related item bias warrants cautious interpretation of specific behaviors, suggesting the need for tailored assessments to enhance diagnostic accuracy and inform preventive interventions. Full article

To assess the therapeutic relevance of BRIP1 in gastric cancer (GC), we examine its functional role in conferring resistance to anoikis within GC cells and elucidate the oncogenic signaling pathways modulated by BRIP1. By integrating the Cancer Genome Atlas (TCGA) and Gene Set Enrichment Analysis (GSEA) databases with Least Absolute Shrinkage and Selection Operator (LASSO) regression, a novel risk score to stratify GC patients based on prognosis was generated, and a significantly differentially expressed gene, BRIP1, was validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR). Protein expression associated with apoptosis, cell cycle, and epithelial-mesenchymal transformation (EMT) was quantified via RT-qPCR and Western blot (WB). 5-Ethynyl-2′-deoxyuridine (EdU) and cell counting kit-8 (CCK-8) assays were conducted to quantify proliferative activity. The protein level in axillary tumor tissues of nude mice was detected by immunohistochemistry (IHC). We established an eight-gene anoikis-related prognostic risk assessment model (DUSP1, VCAN, P3H2, TXNIP, BRIP1, FGD6, GPX3, and RLN2) for GC. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Among these genes, BRIP1 showed significant differential expression between tumor and normal tissues, as well as normal gastric mucosal epithelial cells and GC cells. Mechanistically, BRIP1 conferred anoikis resistance to GC cells by suppressing the generation of reactive oxygen species (ROS). We found that the PI3K inhibitor LY294002 counteracted BRIP1-driven oncogenic effects, which was evidenced by restored expression of key regulators governing apoptosis, cell cycle progression, and EMT, in addition to suppressed proliferation in GC cells. BRIP1 is postulated to function upstream of the PI3K/Akt signaling cascade. This study establishes a risk scoring model and identifies BRIP1 as a potential prognostic marker for GC. Full article