Cadmium (Cd) pollution severely threatens to plant development and human health. As a phytoremediation species, S. portulacastrum possesses outstanding Cd accumulation ability. S. portulacastrum seedings was cultivated with half-strength Hoagland solution with 25 mg/L of CdCl2, with Cd-free medium as control. After 14 days, treated plant kept growing but showed a 43.4% lower growth rate and 1.3 cm shorter roots. Leaf number increased and then decreased, whereas fresh weight increased continuously. The chlorophyll a/b ratio dropped to 1.89, suppressing photosynthesis. To eliminate excess ROS, plants activated comprehensive antioxidant systems: root SOD activity hit 192.64 U/g, root POD and stem CAT activities rose 2.8- and 4.6-fold separately. Cd accumulated predominantly in roots at 622.14 mg/kg, displaying obvious tissue specificity. Transcriptome analysis revealed 2461 and 4545 leaf DEGs, 2215 and 3004 root DEGs after 7 and 14 ds Cd exposure. Combined physiological and transcriptomic data uncovered two core Cd-tolerant mechanisms: metal transporters sequester toxic Cd²⁺ in vacuoles, and antioxidant systems scavenge ROS. Hub genes of key modules were enriched in glutathione metabolism, carbon metabolism, oxidative phosphorylation, peroxisome, protein processing, endocytosis and phenylpropanoid biosynthesis pathways. RT-qPCR validated the expression of representative metal transport and antioxidant hub genes, and heterologous GPX overexpression in yeast INVSc1 verified its function in boosting Cd tolerance. This study provides theoretical support for breeding heavy metal remediation plants via genetic engineering.

This study aimed to investigate the role and mechanism of T-box transcription factor 20 (TBX20) in doxorubicin resistance in breast cancer cells. RNA-seq data from breast cancer samples in the TCGA database were analyzed. Lentiviral vectors were used to establish TBX20 overexpression and silencing models in MCF-7 and MDA-MB-231 cells. Gene and protein expression were detected by qPCR and Western blot, respectively. Cell viability and the half-maximal inhibitory concentration of doxorubicin were measured using the CCK-8 assay. Apoptosis, migration, and invasion were analyzed by flow cytometry, wound healing assay, and Transwell assay. Mitophagy levels were assessed via immunofluorescence staining and western blotting. ChIP and dual-luciferase reporter assays were performed to validate the transcriptional regulation of ABCC1 by TBX20. Results showed that TCGA data analysis revealed a high expression of TBX20 in breast cancer tissues, which was positively correlated with ABCC1 expression. In MCF-7 and MDA-MB-231 cells, TBX20 overexpression significantly enhanced cell proliferation, migration, invasion, and resistance to doxorubicin, while suppressing the expression of mitophagy-related proteins LC3-II/LC3-I, PINK1, and BNIP3. ChIP and dual-luciferase reporter assays confirmed that TBX20 directly binds to and activates the ABCC1 promoter. Silencing of ABCC1 or restoration of mitophagy by CCCP reversed TBX20 overexpression‑induced doxorubicin resistance. TBX20 enhances the resistance of breast cancer cells to doxorubicin by transcriptionally upregulating ABCC1 and is correlated with the suppression of mitophagy.

Postoperative pain (POP) is one of the most common complications of surgical procedures. Using a rat plantar incision model, we investigated the interactions between tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB), and the voltage-gated sodium channel Nav1.8, to uncover the neural basis of POP. Our research demonstrates that, within the dorsal root ganglion (DRG), TNF-α enhances pain behaviors by driving NF-κB-dependent overexpression of Nav1.8 in neurons, further elucidating the molecular basis of POP. This study identifies the TNF-α/NF-κB/Nav1.8 axis as a critical pathway for therapeutic intervention, thereby establishing a theoretical foundation for targeting cytokine signaling to alleviate POP.

Na+/H+ exchanger-3 (NHE3) is a major mediator of electroneutral NaCl absorption in the intestine and colon. In the distal colon, chronic aldosterone exposure suppresses NHE3 expression, but the molecular mechanism responsible for this regulation remains unclear. Here, we tested whether aldosterone represses NHE3 through microRNA-dependent posttranscriptional regulation. Transcriptomic analysis of distal colon from dietary Na+-depleted rats identified miR-204-5P (miR-204-5P) as markedly upregulated. Aldosterone increased miR-204-5P abundance and concomitantly reduced NHE3 mRNA, protein expression, and transport activity in rat and human distal colonic epithelium and in SK-CO15 cells. Bioinformatic and reporter analyses identified a conserved miR-204-5P binding site within the NHE3 3'-untranslated region, and miR-204-5P mimic transfection markedly suppressed NHE3 expression and transport activity without affecting other Na+/H+ exchanger isoforms. These findings identify a previously unrecognized aldosterone-microRNA signaling pathway that mediates chronic repression of NHE3 and provide new insight into hormonal regulation of colonic Na+ absorption.NEW & NOTEWORTHY This study identifies a previously unrecognized aldosterone-microRNA signaling mechanism regulating colonic Na+ absorption. We demonstrate that aldosterone induces miR-204-5P, which directly targets the NHE3 3'-untranslated region and suppresses NHE3 expression and transport activity in distal colonic epithelium. These findings reveal a microRNA-mediated pathway linking mineralocorticoid signaling to long-term inhibition of electroneutral NaCl absorption, providing new insight into hormonal regulation of intestinal electrolyte transport.

Uremic cardiomyopathy (UCM) is a severe complication of uraemia that lacks effective treatments. The role of immune dysfunction in haemodialysis patients with UCM remains unclear. Peripheral blood mononuclear cells (PBMCs) are major components of the immune system; however, they do not directly contact cardiomyocytes. In general, extracellular vesicles (EVs) function as intercellular communication mediators. Therefore, in this study, we first investigated the role of PBMC-derived EVs (PBMC-EVs) in UCM and identified EV-miR-744-5p as a key molecule involved in PBMC-cardiomyocyte communication. Mechanistically, indoxyl sulphate (IS) downregulated miR-744-5p expression in PBMC-EVs, leading to IGF2R upregulation in cardiomyocytes, thereby exacerbating myocardial injury via induction of hypertrophy, apoptosis and inflammatory pathway activation in the cardiomyocytes. We also explored the potential of natural products to treat UCM by modifying PBMC-EVs and found that the traditional Chinese medicine monomer salvianolic acid B (Sal B) could bind to YY1, enhancing miR-744-5p expression in PBMC-EVs and thus mitigating myocardial injury in UCM. Taken together, these findings indicate the critical role of PBMC-EVs in UCM and suggest the cardioprotective effects of Sal B via PBMC-EV modification. They also provide novel insights into immune mechanisms underlying UCM, particularly indicating that targeting PBMC-EVs may be a promising UCM treatment strategy.

Adenomyosis is a chronic gynecological disorder characterized by ectopic endometrial tissue within the myometrium, leading to pelvic pain, menorrhagia, and infertility. Increasing evidence implicates dysregulated Wnt/beta-catenin signaling and aberrant activation of SFRP4+ natural killer T (NKT) cells in disease progression. This study reports the ultrasound-assisted synthesis of a cerium-doped zeolite nanocomplex (Ce-ZNC) and evaluates its therapeutic efficacy in experimental models of adenomyosis. Ce-ZNC was synthesized via an ultrasound-assisted doping approach and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and polydispersity index (PDI) analysis. In vitro studies were conducted on human peripheral blood mononuclear cell (PBMC)-derived SFRP4+ NKT cells. In vivo efficacy was evaluated in a murine adenomyosis model. IGFBP5 expression and Wnt/beta catenin signaling components were analyzed by RT-qPCR and Western blotting. Histological and cytokine analyses were performed to assess fibrosis and inflammation. Ce-ZNC exhibited spherical morphology with nanoscale dimensions and good colloidal stability. Treatment resulted in a dose-dependent suppression of IGFBP5 expression and inhibition of Wnt/beta-catenin signaling. In vivo administration significantly reduced uterine fibrosis, glandular invasion, and inflammatory cytokine levels. These findings suggest that Ce-ZNC exerts immunomodulatory and anti-fibrotic effects in adenomyosis. While promising, further studies are required to elucidate biodistribution, long-term safety, and translational potential in human models. Key words Adenomyosis " Cerium-doped zeolite " Nanomedicine " Wnt/beta-catenin pathway " IGFBP5 " SFRP4+ NKT cells " Inflammation " Fibrosis " Ultrasound-assisted synthesis.

Cadmium (Cd) contamination of orchard soils threatens tree growth, fruit quality and food safety, and strategies are needed to limit Cd accumulation in apple. Grafting is widely used in apple production, but how rootstock-scion interactions regulate Cd uptake and detoxification remains unclear. This study aimed to elucidate the physiological and molecular mechanisms by which different apple graft combinations modulate Cd accumulation and tolerance. Four graft combinations comprising 'Hanfu' (HF) or 'Fuji' (FJ) scions grafted onto Malus baccata (L.) Borkh. (Mb) or Malus micromalus Borkh. (Mm) rootstocks, were grown in nutrient solution with or without 50 μM CdCl₂. Plant growth, Cd2+ influx, Cd accumulation and localization, antioxidant capacity, cell wall composition, and root and leaf transcriptomes were analyzed. Cadmium stress reduced biomass, root system development and photosystem II efficiency but generally increased non-enzymatic antioxidant capacity. The Mb rootstocks showed lower root net Cd2+ influx, lower Cd accumulation in roots and leaves, and weaker Cd signals in xylem than Mm, indicating a greater ability to restrict Cd uptake and transport. Across combinations, root cell walls were the major Cd sink, and Cd exposure increased pectin, hemicellulose and lignin contents. Transcriptome analyses revealed rootstock and scion specific Cd responses, with distinct enrichment of genes related to photosynthesis, oxidative stress and cell wall metabolism. These findings provide a physiological and molecular basis for selecting low-Cd apple graft combinations.

Persistent organic pollutants such as organochlorine pesticides (OCPs) have been implicated in obesity and metabolic dysfunction. As they bioaccumulate in adipose tissue, OCPs may act as obesogens, but in vivo evidence for aldrin, endosulfan and lindane is limited. This study investigated whether subacute exposure to aldrin, endosulfan and lindane elicits obesogenic effects in male rats by examining weight gain, serum biochemistry and metabolic and inflammatory gene expression in white adipose tissue (WAT) and brown adipose tissue (BAT). Thirty-two adult male Sprague-Dawley rats were randomly assigned to receive corn oil (control) or oral aldrin, endosulfan or lindane (1 mg/kg every other day for 28 days). Body weight was recorded weekly. Serum liver enzymes and lipid profile were determined. In WAT and BAT, we quantified mRNA expression of thermogenic and adipogenic markers (Pparg, Ucp1, Ucp3, Fndc5), and the pro- and anti-inflammatory cytokines (Il-1b, Tnf-α, Il-10, Il-4). Lindane caused significant weight gain from the first week (p < 0.0001), whereas aldrin and endosulfan increased body weight only at week four (p < 0.05). Endosulfan-treated rats had reduced total and high-density lipoprotein cholesterol (p < 0.05) without changes in low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, or triglycerides. In WAT, Pparg, Ucp1, and Fndc5 transcripts were unchanged, while Ucp3 tended to decrease in the endosulfan group (p = 0.056). In BAT, endosulfan increased Ucp1 and decreased Fndc5 levels (p < 0.05), with no changes in Pparg or Ucp3. Endosulfan suppressed Il-1b, Tnf-α, and Il-10 (p < 0.05) transcripts in both WAT and BAT, and all pesticides reduced Il-4 expression in BAT (p < 0.05). Overall, short-term exposure to aldrin, endosulfan or lindane interfered with metabolic and inflammatory pathways in a compound-specific manner, with lindane causing early weight gain and endosulfan eliciting complex effects on lipid metabolism and adipose gene expression. We suggest that even short-term exposure to OCPs may affect metabolic regulation in male rats, with each chemical exerting distinct effects.

Esophageal squamous cell carcinoma (ESCC) is a significantly fatal gastrointestinal malignancy worldwide, with complex proteomic remodeling during its onset and progression. Despite advancements in existing multimodal therapy regimens, the prognosis for advanced patients remains inadequate, necessitating the urgent identification of novel therapeutic targets. The Ubiquitin‑proteasome system is the principal regulatory mechanism for intracellular protein homeostasis, with deubiquitinating enzymes (DUBs) serving as crucial 'editors' that reverse ubiquitination modifications, significantly influencing the stability, localization and functional regulation of oncoproteins. This review aims to systematically delineate the complex regulatory network of DUBs in ESCC, comprehensively investigate their specific mechanisms within critical oncogenic signaling pathways, including TGF‑β, Wnt/β‑catenin, NF‑κB and Hippo, as well as their roles in epithelial‑mesenchymal transition, epigenetic remodeling and the regulation of the immune microenvironment. Furthermore, this review provides a novel cross‑cancer perspective by comparing the similarities and differences of DUBs in ESCC and uterine corpus endometrial carcinoma to determine the conserved and tissue‑specific functions of ubiquitin‑specific protease (USP)14, USP7 and BRCA1‑associated protein 1. Furthermore, the preclinical research progress of small molecule inhibitors and proteolysis‑targeting chimeras targeting DUBs was also assessed to identify the theoretical basis and translational pathway for the development of next‑generation precision oncology therapies.

Epidermal stem cell (ESC) degeneration is closely associated with skin aging and functional deterioration. Type XVII collagen (COL17A1) critically regulates ESC polarity and epidermal homeostasis. This study investigated the protective effects of recombinant human COLXVII (rhCol17) against blue light-induced photoaging, particularly on ESC.

Protein prenylation is a critical post-translational modification that controls many cancer-related signalling pathways and represents an important therapeutic target currently lacking effective pharmacological agents. Here, we establish the fluorescent prenyl diphosphate analogue MANT-O-GPP as a multipurpose probe for simultaneous analysis of ligand binding and catalysis in geranylgeranyltransferase I (GGTaseI) and farnesyltransferase (FTase). Using a tryptophan-to-MANT-O-GPP FRET assay, we found that MANT-O-GPP bound to GGTaseI and FTase with high affinity and reported occupancy of the isoprenoid donor site, as confirmed by displacement with the native substrates. In parallel, a FRET-based activity assay employing CFP-tagged protein substrates enabled direct monitoring of prenyl transfer and product formation. Notably, the known inhibitor L-778123 blocked catalysis without displacing MANT-O-GPP, demonstrating that the combined platform distinguishes prenyl-site competitors from inhibitors acting through the adjacent protein-substrate region. This fluorescence-based system provides a practical, mechanistically informative, and high-throughput-compatible platform for prenyltransferase inhibitor discovery.

Benzotriazole ultraviolet stabilizers (BUVSs) are contaminants of emerging concern. Individual BUVSs exert toxic effects in animals; however, little research has examined the effects of BUVS mixtures on aquatic organisms. In this study, zebrafish (Danio rerio) embryos were microinjected with a mixture of five BUVSs - UV-P, UV-326, UV-327, UV-328, and UV-329 to identify effects on early-life-stage development and to elucidate the molecular basis of any adverse effects by integrating non-coding RNA and messenger RNA transcriptomic analyses. The mixture caused dose-dependent effects on development, including increased mortality and malformations, changes in heart rate, accelerated hatching, and altered behavior. Exposure to the mixture altered the expression of non-coding and messenger RNAs. Altered expression of specific long non-coding RNAs (lncRNAs) and developmental microRNAs suggests a coordinated disruption of post-transcriptional gene-expression regulation. These lncRNAs could act as cis regulators or fine modulators of embryogenesis, exacerbating defects in neuromuscular and immune maturation. Suppression of JNK and NF-κB stress pathways points to a mechanism of silent toxicity that compromises cellular defense. Additionally, altered expression of mRNAs indicates that the BUVS mixture induced oxidative stress, potentially leading to DNA damage and developmental defects. This research emphasizes the widespread disruption of the transcriptome by the mixture of BUVSs, including disruption of the non-coding transcriptome, particularly lncRNAs and miRNAs, as a mechanism of embryotoxicity of BUVSs.

Oxaliplatin-based chemotherapy is a principal treatment for colon cancer, but drug resistance hinders its efficacy. Cancer cell dormancy is reportedly a crucial driver of chemoresistance. IL-24 functions vitally in tumor chemoresistance, yet its role in colon cancer dormancy and oxaliplatin resistance remains unexplored.IL-24 expression was assessed in colon cancer tissues and cells via RT-qPCR, western blotting, or immunohistochemistry. The functions of IL-24 in colon cancer cell proliferation, apoptosis, dormancy, and oxaliplatin resistance were evaluated by CCK-8, flow cytometry, and western blotting. The downstream mechanism of IL-24 was predicted using RNA sequencing and bioinformatics analyses and verified in vitro. A tumor xenograft mouse model was built to further verify the role of IL-24 in colon cancer. IL-24 was overexpressed in oxaliplatin-resistant colon cancer tissues and cells. Furthermore, IL-24 treatment reversed the anti-proliferative and pro-apoptotic effects of oxaliplatin on colon cancer cells. Regarding cell dormancy, IL-24 treatment triggered G0/G1 cell cycle arrest and upregulated dormancy markers (CDKN1A, CDKN1B, TGFB2, and MSK1). Bioinformatics analyses revealed that IL-24 might function in colon cancer mainly through NF-κB pathway, and IL-24 activated the NF-κB axis in tumor cells. Importantly, treatment with NF-κB inhibitor reversed IL-24-induced colon cancer cell dormancy and oxaliplatin resistance. In vivo, IL-24 treatment abolished the anti-tumor effects of oxaliplatin, promoted cell dormancy, and activated NF-κB signaling in tumor tissues. IL-24 induces colon cancer cell dormancy and oxaliplatin resistance by activating NF-κB signaling. The IL-24/NF-κB axis may serve as a likely target to alleviate oxaliplatin resistance in colon cancer.

This study investigated the protective effects of dietary supplementation with 2% black cumin (Nigella sativa) oil (BCO) against malathion-induced toxicity in Nile tilapia (Oreochromis niloticus). Over a 72-day feeding trial, fish were divided into four groups: control, 2% BCO, malathion (LC₅₀/20), and malathion + 2% BCO. The results demonstrated that sublethal malathion exposure significantly impaired growth performance including final weight, weight gain, and specific growth rate and worsening the feed conversion ratio. Hematological analysis revealed a severe anemic response, marked by significant reductions in red blood cell (RBC) counts, hemoglobin (Hb), and hematocrit (Hct) levels. Furthermore, malathion induced profound hepatic and metabolic dysfunction, evidenced by elevated serum AST, ALT, ALP, glucose, and cholesterol levels. Oxidative stress was prominent in the malathion-exposed group, characterized by suppressed antioxidant enzyme activities (SOD, CAT, GPx) and a severe increase in lipid peroxidation (MDA). Molecular assessments of brain tissue showed a marked upregulation of pro-inflammatory (il-1β, tnf-α) and apoptotic (caspase-3) genes, indicating neuroinflammation. Histopathological examinations confirmed severe multi-organ damage, including branchial lamellar fusion, hepatic necrosis, renal tubular degeneration, and brain hyperemia. Conversely, dietary supplementation with 2% BCO significantly ameliorated these toxic effects. Notably, BCO supplementation effectively restored growth parameters and FCR to levels statistically comparable to the control group, normalized hematological and biochemical profiles, bolstered antioxidant defenses, and significantly downregulated neuroinflammatory and apoptotic gene expressions, thereby preserving overall tissue architecture. In conclusion, this study demonstrates that dietary Nigella sativa oil effectively mitigates malathion-induced toxic effects. Rather than presenting individual components as entirely novel, the true strength and novelty of this approach lie in the multi-systemic integration of tissue histopathology with underlying neuroinflammatory and apoptotic gene expressions in the brain, offering a comprehensive insight into the protective mechanisms of black cumin oil in aquaculture.

Quasi-ultrafine particles (qUFPs; particulate matter < 0.49 μm; PM0.49) exposure is a key environmental contributor to cardiovascular disease, but its epigenetic impact on human cardiac fibroblasts (HCFs) remains unclear. Dysregulated DNMT activity and aberrant DNA methylation have been implicated in fibroblast activation and cardiac remodelling; however, the clinical utility of the DNMT inhibitor 5-Azacytidine (5-Aza) remains limited by chemical instability and toxicity, motivating nanoparticle (NP)-based delivery to improve stability and sustain therapeutic exposure. PM0.49 was collected from Chiang Dao district, Chiang Mai Province, Thailand. HCFs were exposed to PM0.49 (low and high concentrations), with or without pre-treatment using free 5-Aza or 5-Aza-loaded hyaluronic acid nanoparticles (5-Aza-NP). Epigenetic and pro-fibrotic gene markers were quantified using RT‑qPCR, and cell viability was assessed by MTT assay. Additionally, transcriptomic analysis using bulk RNA sequencing was performed to evaluate the effects of PM0.49 on HCFs and their modulation by 5-Aza-NP treatment. HCFs exposed to high concentrations of PM0.49 exhibited dysregulation of DNA methylation machinery, characterised by increased expression of DNMT1 and DNMT3A/B. Markers associated with fibroblast activation and pathogenic activation, including COL1A1 and α-SMA, were significantly induced following PM0.49 exposure, whereas these alterations were attenuated following 5-Aza treatment. NP-based delivery of 5-Aza attenuated PM0.49-induced HCF activation with reduced cytotoxicity under chronic exposure conditions. Bulk RNA sequencing identified transcriptomic alterations associated with PM0.49 exposure that were partially modulated by 5-Aza-NP treatment, with selected findings validated by RT-qPCR. Exposure to a smoke haze-period PM0.49 preparation from a biomass burning-affected rural site in Chiang Mai, Thailand, induced pathogenic HCF activation with molecular findings consistent with dysregulation of DNA methylation machinery. 5-Aza-NP attenuated PM0.49-induced fibroblast activation and modulated associated transcriptomic alterations, suggesting a potential epigenetic-based therapeutic strategy against PM0.49-induced cardiac fibroblast dysfunction. These findings warrant further validation across diverse PM compositions and sampling conditions.

The cattle tick Rhipicephalus microplus is a major ectoparasite affecting livestock worldwide, and its increasing resistance to synthetic acaricides has intensified the search for plant-derived alternatives. Although the hydroalcoholic seed extract of Randia aculeata has demonstrated acaricidal activity, its molecular effects in ticks remain poorly understood. This study evaluated the acaricidal activity of the extract and the underlying molecular mechanism against R. microplus larvae.

Hepatocellular carcinoma (HCC) is the predominant form of cancer globally, characterized by a dismal prognosis and few treatment options. Agomelatine (AGO) acts as a melatonin receptor agonist and a 5-HT2C receptor antagonist, suggesting its potential anticancer efficacy across diverse cancer types.

Cold stress severely impairs the growth and metabolic composition of tea shoots, thereby limiting tea production. The application of exogenous regulatory substances offers a potential strategy to mitigate cold-induced damage in tea plants. Therefore, identifying endogenous metabolites that could increase cold tolerance and exploring their working mechanisms would be of interest. Here, we identified 292 differentially accumulated metabolites in young shoots of two different tea cultivars through UPLC-MS/MS assays, among which amino acid metabolism was found to be markedly altered. Further analysis revealed that leucine was dramatically induced in all 10 tested accessions. Phenotype, relative electrolyte leakage (REL), and maximum quantum yield of photosystem II (Fv/Fm) analyses revealed that pre-treatment with 20 mM leucine significantly increased the cold tolerance of young shoots in 4 different cultivars. Transcriptome analysis revealed that 48.06% of differentially expressed genes (DEGs), including calcium (Ca2+) signaling, sugar conversion, and reactive oxygen species (ROS) scavenging pathways, were similarly induced by leucine pretreatment in both tolerant and sensitive cultivars. However, 51.94% DEGs involved in phenylpropanoid biosynthesis, glutathione metabolism, and tyrosine metabolism were differentially expressed. Moreover, free amino acid detection also revealed great differences among tolerant and sensitive cultivars. Taken together, our results demonstrate that exogenous application of 20 mM leucine, a cold-inducible endogenous metabolite, effectively mitigates cold-induced damage in both tolerant and sensitive cultivars through common and cultivar-specific mechanisms. These findings supported the development of leucine as a promising cold resistance agent for mitigating the effects of cold spells on young shoots in fields.

Reliable biomarkers that predict therapeutic response remain a major unmet need in epithelial ovarian cancer (EOC), particularly for patients receiving neoadjuvant chemotherapy (NACT). Although high-throughput multi-omics technologies have accelerated biomarker discovery, the translation of candidate markers into clinically actionable predictors remains limited. Here, we developed an integrative multi-omics framework combining single-cell RNA sequencing, bulk transcriptomic profiling, and machine-learning-based modeling to identify biomarkers associated with chemotherapy response in EOC. Single-cell analyses were used to delineate cellular heterogeneity and intercellular communication landscapes before and after NACT, while bulk cohorts were leveraged to validate response-associated molecular signatures. Network-based and pathway analyses were applied to prioritize functionally relevant candidates. We identified integrin subunit alpha 1 (ITGA1) as a response-associated candidate with notable discriminatory performance for chemotherapy response and functional relevance in cisplatin-resistant ovarian cancer models. ITGA1-related signatures stratified patients by therapeutic response and were associated with immune and stress-response pathways, extracellular matrix signaling, and altered cell-cell communication patterns. Functional experiments showed that ITGA1 knockdown restored cisplatin sensitivity and suppressed clonogenic survival, migration, adhesion, and apoptosis evasion in resistant ovarian cancer cells. Together, our study supports ITGA1 as a response-discriminatory and functionally relevant biomarker candidate for chemotherapy response in EOC and highlights the value of integrating single-cell and bulk multi-omics data with machine-learning approaches. These findings provide a translational framework for patient stratification and experimental prioritization in ovarian cancer.

Triple-negative breast cancer (TNBC) is highly malignant and exhibits significant heterogeneity. It readily develops resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy. This review summarizes the primary resistance genes associated with treatment failure in TNBC, along with their fundamental characteristics and mechanisms of action. Most genes are overexpressed in TNBC and mediate cancer cell proliferation, survival, and drug resistance by regulating DNA damage repair, tumor stem cell properties, microtubule stability, and the abnormal activation of pathways. Focusing on key drug resistance genes such as PSENs, ATM, PIK3CA, and CDK4/6, we discovered that they promote tumor growth and metastasis by abnormally activating the Notch, Wnt/β-catenin, and PI3K/Akt/mTOR pathways. In response, targeted intervention strategies for drug-resistant genes have been proposed, including small-molecule inhibitors such as γ-secretase inhibitors and dual mTOR/PI3K inhibitors, as well as combination therapies involving Akt inhibitors and PD-1/PD-L1 inhibitors. They can suppress the expression of relevant genes, block drug resistance pathways, and restore drug sensitivity, providing a viable pathway and theoretical basis for TNBC treatment.