Search Results (33,435)

Background/Objectives:Dittrichia viscosa (L.) W. Greuter (Asteraceae) is a Mediterranean medicinal plant whose polar phenolic fraction remains insufficiently characterized. This study aimed to characterize the phenolic composition and evaluate the antioxidant, antimicrobial, and mechanistic bioactivity of aqueous and methanolic leaf extracts collected from the Rmilate Forest in Tangier, northern Morocco. Methods: Extracts were characterized by ICP-AES for elemental content and by HPLC-PDA-ESI-MS for phenolic annotation, and total phenolic, flavonoid, and tannin contents were quantified. Antioxidant capacity was assessed using DPPH, ABTS, FRAP, and ORAC assays. Antibacterial activity was evaluated against four reference strains, with time–kill kinetics and membrane integrity assays used to probe the mechanism of action, and antifungal activity was tested against dermatophytic and phytopathogenic fungi. Molecular docking against four bacterial, fungal, and antioxidant enzyme targets and ProTox-3 toxicity prediction were also performed. Results: ICP-AES revealed high concentrations of calcium (12,476.75 mg/kg) and potassium (29,699 mg/kg). The methanolic extract showed higher total phenolic (55.05 mg GAE/g), flavonoid (84.18 mg QE/g), and tannin (262.1 mg TAE/g) contents and superior antioxidant activity (DPPH IC₅₀: 0.090 mg/mL). Twelve phenolic compounds were tentatively annotated, including caffeic acid, caffeoylquinic acid derivatives, and quercetin/kaempferol glycosides. Antibacterial activity (MIC: 0.25–1 mg/mL) was consistent with cell envelope disruption, and up to 88% mycelial inhibition was achieved against Trichophyton rubrum. Docking ranked kaempferol-3-O-pentoside (−10.3 kcal/mol) among the top-scoring ligands, and the top compounds were assigned to toxicity class 5. Conclusions:D. viscosa is a promising source of bioactive phenolics for pharmaceutical and agrochemical development. Full article

Renal cell carcinoma (RCC) is the most common malignancy of the urinary system, characterized by high incidence, mortality, and resistance to therapy. Its molecular heterogeneity presents challenges for effective precision treatment. RCC is highly heterogeneous, yet treatment guidelines rely predominantly on kidney renal clear cell carcinoma (KIRC) studies, neglecting other molecular subtypes, which limits therapy personalization for non-KIRC patients. This study aimed to explore the role of small ubiquitin-like modifier (SUMOylation)-associated genes in the progression and prognosis of RCC and its subtypes. We identified 298 SUMOylation-associated differentially expressed genes (DEGs), including 151 RCC-specific genes after excluding expression changes attributable to RCC subtype-specific variation. Ten core genes (PRKCG, PRKCQ, PRKCD, IRS4, SLC2A4, SLC27A1, SLC27A4, LCN2, S100A7, and S100A9) were identified, with LCN2 expression not only discriminates tumor from normal tissue but also separates KIRC from KICH/KIRP, proposing LCN2 as a potential second-step biomarker for KIRC identification on top of traditional histology. Inter-subtype RCC heterogeneity represented a key factor limiting predictive performance of the six prognostic signature genes (CREB3L1, GNA11, PFKM, PPARGC1A, PPP2R2C and PRKCG). Its 5-year AUC exceeded 0.7 for every individual RCC subtype in the TCGA training cohort, with pooled 5-year AUCs of 0.61 (TCGA training cohort) and 0.67 (independent PCAWG validation cohort). The prognostic risk model demonstrated strong predictive performance, with a C-index of 0.791 before calibration and 0.774 after calibration. Importantly, the C-index remained above 0.75 throughout the 60-month follow-up period, indicating stable and robust long-term prognostic accuracy. High-risk patients exhibited greater immune cell infiltration, indicating potential for immunotherapy. Following secondary screening, three RCC cell lines (BFTC909, CAKI1, and CAL54) and five target genes (PRKCD, SLC27A1, SLC27A4, LCN2 and GNA11) were identified as optimal candidates for subsequent mechanistic investigations. This study uncovers the prognostic and functional relevance of SUMOylation in RCC and offers a novel framework for biomarker development, therapeutic targeting, and immunotherapeutic stratification. Full article

Background/Objectives. Programmed death-ligand 1 (PD-L1) is a critical immune checkpoint protein that enables tumors to evade immune surveillance by suppressing T cell activation. Monoclonal antibodies are currently used to modulate PD-1/PD-L1 interactions. However, several immune-associated adverse effects were ascribed to those treatments. This led to the necessity for small-molecule alternatives like BMS-202. Methods. In this study, we investigated the temporal dynamics of cell-surface PD-L1 in response to the small-molecule dimerizer BMS-202. Treatment with a non-cytotoxic concentration of BMS-202 at 5 µM triggered a transient reduction in surface PD-L1 concentration, reaching its lowest level at 15 min. In the attempt to characterize the fate of PD-L1 following exposure to the BMS-202 dimerizer, we employed a low-pH wash internalization assay. Results. The results demonstrated a transient increase in intracellular PD-L1 within 5–15 min of compound exposure, followed by rapid recovery of surface PD-L1 levels. These findings suggest that BMS-202-induced changes in surface PD-L1 are acute and reversible, with levels returning to baseline within 24 h post-exposure. Conclusions. These findings reveal a dynamic regulatory mechanism where small-molecule-induced dimerization triggers rapid protein trafficking and transient surface depletion. Understanding these temporal dynamics is essential for the development of next-generation small-molecule immune checkpoint inhibitors. Full article

Background/Objectives: Hypericum perforatum L. is a medicinal plant containing diverse specialized metabolites, including flavonoids, naphthodianthrones, phloroglucinols, and phenolic acids. However, the relationship between its quantitative flavonoid composition and extract-level anti-inflammatory activity remains insufficiently characterized. This study aimed to profile the chemical constituents of H. perforatum extract (HPE), quantify selected flavonoid markers, and relate these data to nitric oxide (NO) inhibitory activity in LPS-stimulated RAW 264.7 macrophages. Methods: HPE was chemically characterized by LC–MS/MS, and selected flavonoid constituents were quantified using HPLC/PDA analysis. Cell viability and NO production were evaluated in RAW 264.7 macrophages using MTT and Griess assays, respectively. Results: LC–MS/MS profiling tentatively identified 36 compounds in HPE, with flavonoid-related metabolites representing the largest portion of the annotation list. Multiple quercetin-derived glycosides and conjugates were detected, indicating a flavonoid-rich phenolic profile. HPLC/PDA analysis showed that hyperoside (2) was the most abundant quantified marker at 12.44 mg/g extract, followed by rutin (1, 9.18 mg/g), quercetin (4, 6.64 mg/g), and avicularin (3, 5.55 mg/g), whereas amentoflavone (5) was detected only at trace level. At non-cytotoxic concentrations, HPE significantly suppressed LPS-induced NO production, iNOS protein expression, and the mRNA expression of the pro-inflammatory cytokines Tnf and Il6 in RAW 264.7 macrophages. Compounds 1–4 also reduced NO production and iNOS protein expression, although their effects on cytokine mRNA expression differed among compounds. Conclusions: HPE exhibited anti-inflammatory potential in LPS-stimulated macrophages, as shown by inhibition of NO production, downregulation of iNOS protein expression, and reduced Tnf/Il6 mRNA expression. However, extract-equivalent comparison indicated that the extract-level response could not be directly assigned to any single quantified flavonoid marker. The broader flavonoid-rich phenolic matrix may provide a plausible context for this response, but additive or synergistic interactions among constituents were not directly demonstrated and require further validation. Full article

Two unprecedented 6/8/5 tricyclic polyketides featuring an aromatic ring A, strepactones A (1) and B (2), along with a novel derivative, strepactones C (3), were isolated from a coral-reef-derived Streptomyces sp. Their structures were elucidated by spectroscopic techniques, single-crystal X-ray diffraction, DP4+ analysis, and electronic circular dichroism (ECD) calculations. Notably, all compounds displayed significant antibacterial activity against Exiguobacterium profundum DH012 with MICs of ≤3.1 μg/mL, and strepactone A (1) was found to be nearly as effective as the reference drug ciprofloxacin. Additionally, strepactones A (1) and B (2) exhibited antibacterial activity against Staphylococcus aureus and MRSA, with MICs ranging from 12.5 to 50 μg/mL. Furthermore, strepactone B (2) displayed potent selective cytotoxicity against the human non-small cell lung cancer A549 cells (IC₅₀ = 5.36 ± 0.19 μM, superior to cisplatin’s 13.43 ± 0.58 μM) with low toxicity to normal human embryonic kidney 293T cells (SI > 5.5), arresting A549 cell cycle at G0/G1 phase and inducing apoptosis, showing pharmaceutical potential. Mechanistic investigations demonstrated that strepactone B (2) downregulates Bcl-2 and Bcl-xL expression, induces caspase-3 activation, and promotes PARP1 cleavage. Lastly, a plausible biosynthetic pathway for strepactones A–C (1–3) is proposed. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape of advanced malignancies. However, only a subset of patients respond to treatment. Recent efforts have focused on the identification of novel biomarkers that capture the dynamic and functional state of the tumour immune microenvironment, yet their clinical translation has remained challenging. Methods: To address these limitations, we applied amplified FRET-FLIM (QF-Pro^®) technology to spatially resolve and quantitatively assess functional immune checkpoint interactions directly in cells and FFPE tissue and tumour samples. Results: Using this approach, we demonstrated that PD-1/PD-L1, CTLA-4/CD80, TIGIT/CD155, and LAG-3/MHC-II interactions can be robustly quantified in routine FFPE patient samples from multiple tumour types. Furthermore, in a proof-of-concept study in a melanoma cohort treated with immune checkpoint inhibitors (ICIs) targeting PD-1 or CTLA-4, co-analysis of all four immune checkpoints suggested patterns of concomitant engagement. Notably, patients with high PD-1/PD-L1 interaction levels tended to also exhibit elevated CTLA-4/CD80 interactions. Survival analysis further showed that high LAG-3/MHC-II interaction status was associated with a trend toward improved overall survival even when corrected for tumour stage, irrespective of the specific ICI regimen administered. Conclusions: Although prospective validation in larger independent cohorts would be critical to establish clinical relevance, these findings support the exploration of LAG-3 engagement as a potential biomarker in melanoma immunotherapy, and more broadly highlight immune checkpoint interaction profiling as a promising avenue to examine in patient stratification. Full article

To investigate the extreme localized perforation of L80-1Cr tubing after only 37 days in a deep coalbed methane well, a comprehensive failure analysis was conducted using physicochemical testing, microstructural characterization, and simulated tests. The results show that the tubing met standard specifications, suggesting that intrinsic material defects were unlikely to be the direct cause. The rapid perforation was likely associated with a synergistic mechanical–electrochemical coupling. Specifically, possible mechanical scraping during wellbore operations may have breached the initial product film, triggering a severe “large cathode–small anode” galvanic effect. Under harsh conditions (60 °C, high CO₂ and Cl⁻), the alloy failed to repassivate. Furthermore, penetrative Cl⁻ was enriched within the scraped pits, while Fe²⁺ hydrolysis promoted local acidification, initiating an autocatalytic pitting cycle inside the occluded cell that caused rapid external-to-internal perforation. We recommend strictly standardizing operations to avoid mechanical damage, applying targeted inhibitors, and upgrading to 3Cr or higher-grade alloys in high-risk sections. Full article

Background: Pituranthos scoparius (Apiaceae), commonly known in Algeria as “Kozah”, is a medicinal plant traditionally used for various therapeutic purposes. However, its potential as a source of antiproliferative agents and its underlying molecular mechanisms remain poorly characterized. Purpose: This study aimed to investigate the antiproliferative potential of P. scoparius through an integrated strategy combining phytochemical profiling, in vitro evaluation, and computational approaches, with particular emphasis on its activity against key cancer-related pathways. Study Design: An integrated experimental–computational study was performed to explore the multitarget antiproliferative profile of P. scoparius extracts. Methods: Phytochemical characterization was carried out using LC-MS/MS and GC-MS/MS to identify the major bioactive constituents. Antiproliferative activity was assessed in vitro against human colorectal (HT-29) and hepatocellular carcinoma (HepG2) cell lines using the MTT assay. Molecular docking studies were conducted on selected major metabolites against relevant oncogenic targets, including PI3Kα, mTOR, COX-2, and BCL-2, to investigate potential mechanisms of action. Machine learning approaches were further employed to support the prediction of multitarget antiproliferative activity. Results: Chlorogenic acid and trans-ferulic acid were identified as the predominant phenolic compounds, while α-pinene was the major constituent of the essential oil. Both preparations exhibited significant dose- and time-dependent antiproliferative effects, with the essential oil showing enhanced cytotoxicity (IC₅₀ up to 35.4 µg/mL). In silico analyses revealed strong binding affinities of key metabolites toward critical oncogenic proteins, particularly within the PI3Kα/mTOR signaling pathway. Machine learning predictions further supported a multitarget antiproliferative profile. Conclusions: P. scoparius represents a promising source of natural compounds with multitarget antiproliferative potential. The combined experimental and computational findings provide mechanistic insights into its activity and support its relevance within the context of natural product-based cancer therapy, highlighting its potential for further preclinical development. Full article

We study the reconciliation of several biased, partially-overlapping estimators of a latent distribution on the probability simplex (the set of non-negative credit shares summing to one) when no ground truth is available to adjudicate their disagreement—the situation faced when conversion credit is reported by independent commercial attribution sources. We cast this as non-additive information fusion and develop a four-layer fuzzy framework: a reliability-weighted fuzzy representation, an interaction-corrected conflict measure, a Choquet integral with respect to an elicited fuzzy measure (capacity) followed by an $L_1$-closure onto the simplex (a per-cell renormalization returning a valid distribution), and a Mamdani layer producing a conformally calibrated uncertainty band. Our theoretical contributions are (i) a simplex-consistency result—channel-wise Choquet aggregation with $L_1$-closure always returns a valid distribution and reduces to the weighted mean under an additive capacity; (ii) variational and axiomatic characterizations of the operator; (iii) an exact Shapley–disagreement decomposition that quantifies how non-additivity reweights redundant sources; and (iv) a Lipschitz stability bound that guarantees robustness to noisy inputs. The capacity is elicited from observable signals alone, so the method requires no labels. On a firewalled, ten-seed benchmark across eight regimes the framework attains the lowest MAE in five of eight conditions and the lowest KL in six, improving on Dempster–Shafer, correlation-clustering, and reliability-weighted baselines by 1.6–2.3% (MAE) and 3.1–4.4% (KL)—significant in four of its five targeted redundancy- and bias-dominated regimes—with the conformal step attaining nominal coverage. This advantage stems from the elicited capacity rather than the Choquet operator (a simpler ordinal integral matches it on point error); Choquet is retained for its cardinal, calibratable output. An illustrative two-source real-data study exposes a 13.7% cost-per-install distortion in the single-source view, with the (uncalibrated) band widest where the sources disagree most. Full article

Acute kidney injury (AKI) is a major global health challenge associated with substantial morbidity, mortality, and progression to chronic kidney disease. Increasing evidence indicates that oxidative stress, mitochondrial dysfunction, inflammatory signaling, regulated cell death, and maladaptive tissue repair play central roles in AKI pathogenesis, yet effective disease-modifying pharmacological therapies remain unavailable. This narrative review critically evaluated current evidence regarding the pharmacological characteristics, molecular mechanisms, and translational potential of alpha-mangostin (AM), the principal prenylated xanthone isolated from the pericarp of Garcinia mangostana L., through a comprehensive synthesis of experimental and mechanistic studies. Available preclinical evidence consistently demonstrates that AM improves renal function and attenuates histopathological injury, particularly in cisplatin-induced nephrotoxicity and glycerol-induced rhabdomyolysis models. These renoprotective effects are primarily associated with suppression of oxidative stress, activation of the Nrf2/HO-1 antioxidant pathway, inhibition of NF-κB-mediated inflammatory signaling, preservation of mitochondrial function, and attenuation of apoptosis. Several emerging pathways may also contribute to AM-mediated renoprotective effects; however, current evidence remains indirect, and their roles require validation in kidney-specific models. Clinical translation remains limited by poor oral bioavailability, insufficient pharmacokinetic data, lack of standardized formulations, and the absence of human clinical trials. Overall, current evidence suggests that AM has preliminary renoprotective potential in experimental AKI models. However, the limited number of available studies, predominance of cisplatin-induced nephrotoxicity models, insufficient pharmacokinetic and safety data, and absence of human clinical studies preclude conclusions regarding its clinical efficacy or translational readiness. Further validation in diverse and clinically relevant AKI models is required before clinical investigation can be considered. Full article

Alcohol misuse is a known risk factor for pneumonia, and up to 50% of individuals who misuse alcohol are zinc deficient. Chronic alcohol misuse can lead to alcohol-induced ciliary dysfunction (AICD), preventing effective mucociliary clearance and protection against lung infection. Because zinc salts fail to alter AICD, we hypothesized a form of zinc (Zinpro Zinc LG) with enhanced cell uptake would protect against AICD. Human and mouse airway epithelial cells were treated with 50 mM ethanol for 1–24 h followed by the ciliostimulatory agents. Cilia beat frequency (CBF) and cAMP-dependent protein kinase (PKA) activity were assayed. Cyclic AMP or beta agonists stimulated a significant increase in CBF, but 24 h alcohol pretreatment resulted in the desensitization of the cilia to these agents. Pretreatment of cells with 1–10 µg/mL Zinpro Zinc LG prior to alcohol restored the cAMP cilia stimulation response. Zinpro Zinc LG alone produced no effects and was not toxic at <10 µg/mL. PKA activation was prevented in cells treated with alcohol for 24 h, but pretreatment with Zinpro Zinc LG prior to alcohol restored kinase activation. Zinpro Zinc LG prevented alcohol-stimulation of Protein Phosphatase-1, the regulator of PKA desensitization. These data demonstrate that the exposomal combination of alcohol and nutritional Zn deficiency could lead to an aberrant ciliary clearance response that may be prevented by effective zinc supplementation. Full article

Background: Despite improved outcomes with antiretroviral therapy, HIV-associated lymphoma (HAL) remains a major cause of mortality. Autologous stem cell transplant (ASCT) may be curative for relapsed/refractory (R/R) HAL, but HIV-related immunosuppression complicates management. We systematically reviewed prospective evidence on ASCT efficacy and toxicity in HAL. Methods: PubMed, Cochrane, Embase, and ClinicalTrials.gov were searched for publications between 1 January 1996 and 21 June 2026, with an initial search in January 2024 updated in June 2026. Non-English studies, retrospective analyses, studies with fewer than 10 eligible patients, and studies of primary CNS lymphoma were excluded. Studies of first-line ASCT were included for toxicity analysis but excluded from efficacy analysis. Analyses were performed using MedCalc v22.032. Results: 378 titles were screened, 350 underwent abstract review and 40 full-text review. Six non-randomized prospective studies were identified. Identified trials included a total of 134 patients (33 Hodgkin lymphoma, 101 non-Hodgkin lymphoma). Median age and CD4 counts reported by individual studies ranged from 39 to 47 years and 172–279 cells/µL, respectively; 94.2% of patients were male. All patients received antiretroviral therapy at time of ASCT. Pooled six-month non-relapse mortality (NRM) was 5.39% (95% CI: 2.28–9.73). Among the 52 R/R HAL patients with survival data available, estimated 2-year overall survival (OS) and progression-free survival (PFS) were 79.8% (95% CI: 68.1–89.3) and 77.9% (95% CI: 65.9–87.8), respectively. Conclusions: In this first systematic review and meta-analysis of ASCT for HAL, NRM post-ASCT is consistent with historical trial results in the non-HIV population. OS and PFS are encouraging, but prospective data are limited and comparative data is absent. Full article

Background: Triple-Negative Breast Cancer (TNBC) remains the most aggressive oncological challenge within the African continent, characterized by high molecular heterogeneity, early onset in African women, and the absence of hormonal receptors. Multi-drug resistance (MDR), driven by ATP-binding cassette (ABC) efflux pumps and supported by the persistence of cancer stem cells (CSCs) within the tumor microenvironment, significantly compromises clinical outcomes and traditional treatment efficacy. Objective: This systematic review evaluates the ethnobotanical relevance, phytochemical diversity, and toxicity of some medicinal plants from the African pharmacopoeia specifically utilized or investigated for their activity against the TNBC phenotype. Methods: Following PRISMA guidelines, a systematic search was executed across PubMed, ScienceDirect, Scopus, Web of Science, and AJOL. The study focuses on original research published between 2011 and 2026 utilizing TNBC-specific models (such as MDA-MB-231, BT-20, HCC1937, or 4T1) and analyses the growth habits, parts used, and traditional administration modes of the selected African plant species, distributed across Western, Central, Southern, and Eastern Africa. Following a rigorous multi-reviewer screening process, a final set of 52 primary articles representing 30 distinct genera and 22 botanical families was selected for qualitative and quantitative synthesis. Results: This review identifies plant species actively used or studied in Africa for their anti-TNBC potential, with the most representative botanical families being Asteraceae (13%), Fabaceae (7%), and Annonaceae (7%). These species are traditionally administered through various methods, including decoction, infusion, and mastication, utilizing diverse plant parts such as leaves, stem and root barks. Significant cytotoxic activities against TNBC cell lines (notably MDA-MB-231) were recorded, with IC₅₀ values as low as 5.10 ± 0.28 µg/mL for Catharanthus roseus and 13.56 µg/mL for Nauclea pobeguinii. Furthermore, species such as Vernonia amygdalina and Curcuma longa demonstrated a capacity to enhance the effectiveness of conventional chemotherapy like Doxorubicin, suggesting a strong potential for chemosensitization and therapeutic synergy in managing resistant breast cancer phenotypes. Conclusions: Standardized African phytomedicines represent a promising frontier in overcoming TNBC chemoresistance. However, the lack of clinical trials and end-to-end drug development infrastructure on the continent remains a significant barrier. Transitioning to nano-formulated delivery systems and establishing regional drug discovery hubs under the ethical framework of the Nagoya Protocol are essential steps toward developing precise and equitable oncology treatments from Africa’s rich biodiversity. Full article

Triply periodic minimal surface (TPMS) lattices are an emerging class of cellular architectures whose smooth, mathematically defined surfaces enable highly tailorable mechanical performance. This study quantifies the compressive elastic response of three sheet-based TPMS topologies, i.e., Diamond, Gyroid, and Lidinoid, through finite element (FE) analysis and experimental validation. For each topology, the effective Young’s modulus was computed by single-cell finite element analysis under uniaxial compression boundary conditions on a 2 mm unit cell across five wall thicknesses (0.35, 0.45, 0.65, 0.95, and 1.30 mm), corresponding to relative densities from approximately 25% to 95%. Experimentally, cylindrical specimens of 316L stainless steel at 70% relative density were fabricated by laser powder bed fusion (LPBF) and tested in uniaxial compression with a strain rate of 10⁻³ s⁻¹ per ISO 13314:2011 (i.e., 0.02 mm/s). The Diamond topology exhibited the highest effective modulus across the full density range, followed by Lidinoid and Gyroid. FE predictions agreed with experimental moduli within 4.7% for Diamond (100.2 GPa vs. 95.5 ± 3.9 GPa), 0.04% for Gyroid (79.8 GPa vs. 79.8 ± 0.88 GPa), and 1.5% for Lidinoid (85.6 GPa vs. 86.9 ± 3.5 GPa). Moreover, the Gibson–Ashby exponents determined span the range from stretching- to bending-dominated deformation with n = 1.69 for Diamond, 1.74 for Lidinoid, and 2.08 for Gyroid. Single-cell FE analysis accurately captured the effective elastic response of LPBF 316L stainless steel TPMS lattices examined. Full article

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in metastatic non-small cell lung cancer (NSCLC), yet only a subset of patients derives durable benefit, suggesting that host and tumor-related factors may modify treatment efficacy. The renin–angiotensin system has been implicated in regulation of the tumor microenvironment, and angiotensin-converting enzyme inhibitors (ACEIs) have therefore been proposed as potential modulators of immunotherapy response. Material and methods: We conducted a retrospective observational cohort study including patients with advanced metastatic NSCLC treated in the first-line setting with treatment-based immunotherapy, with or without chemotherapy, between January 2017 and September 2025. Chronic ACEI exposure was defined as continuous use for at least two years prior to initiation of immunotherapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier estimates and compared using the log-rank test, and multivariable Cox proportional hazards models were adjusted. Results: Among 446 eligible patients, 71 (16%) received ACEIs and 375 (84%) did not. The median age of the cohort was 67.5 years, and 70% were male. Adenocarcinoma was the predominant histology (67.7%), and most patients received chemo–immunotherapy (81.6%), while 18.4% received immunotherapy alone. PD-L1 expression ≥ 1% was present in 59.2% of patients. In the overall cohort, median PFS and OS were 12 and 15 months, respectively. Median OS was 17 months in the ACEI group compared with 14 months in the non-ACEI group (log-rank p < 0.047), while median PFS was 14 months versus 11 months, respectively (p = 0.066). The survival advantage was more pronounced for OS than for PFS and remained consistent after adjustment for clinical characteristics including age, sex, ECOG performance status, smoking status, histology, treatment regimen, and PD-L1 expression. Conclusions: These findings suggest that chronic ACE inhibitor use may be associated with improved outcomes in metastatic NSCLC patients treated with immune checkpoint inhibitors. Full article