Search Results (848)

Introduction: Establishing baseline descriptions of inorganic elements in the early life stages of sharks and in their respective nursery areas is essential for assessing anthropogenic impacts and supporting conservation strategies. Objectives: This study presents the first baseline of plasma trace element concentrations (Al, Zn, As, Cu, Cr, Cd, Co, Mn, Ti, Ni, Hg, Pb) for four juvenile shark species (Carcharhinus limbatus, Paragaleus pectoralis, Rhizoprionodon acutus, and Sphyrna lewini) from Sal Rei Bay, Boa Vista Island, Cabo Verde—the first multi-species shark nursery area described in Atlantic Africa. Methodology: Seawater and sediment samples were collected from eight sites and analyzed along with plasma samples using total reflection X-ray fluorescence spectroscopy (TXRF). Sediment granulometry and pollution indices, including the enrichment factor (EF), ecological risk index (RI), and metal pollution index (MPI), were used to characterize habitat contamination. Data were analyzed using statistical models to explore spatial and element-specific patterns. Results: Overall, environmental contamination was low, with slight increases in Cd, Co, and Hg at sites 1 and 2, near the fishing port, and at site 5, likely reflecting natural transport, sediment redistribution, and enhanced nearshore deposition. Juvenile sharks exhibited generally low plasma trace element concentrations, although species-specific elemental signatures were evident: elevated levels of Al and Cu in C. limbatus, Zn in S. lewini, and As in R. acutus and P. pectoralis. Conclusions: These findings establish critical baseline reference values for trace elements in juvenile sharks from a key Atlantic nursery area. The results provide an essential framework for future biomonitoring efforts and contribute to the management and conservation of Cabo Verdean shark nursery habitats. Full article

Background/Objectives: The emergence of drug-resistant Plasmodium falciparum highlights the need for new antiplasmodial compounds with distinct mechanisms of action. Microbial secondary metabolites, particularly from Streptomyces species, remain important sources of bioactive molecules. This study aimed to evaluate antiplasmodial metabolites associated with a Mongolian Streptomyces isolate. Methods: Streptomyces sp. strain D10 was isolated from Mongolian soil samples and extracted with ethyl acetate. Bioassay-guided fractionation was performed, followed by LC–HRMS analysis and GNPS-based spectral dereplication. Antiplasmodial activity was evaluated against P. falciparum 3D7, K1, and Dd2 strains using a SYBR Green I assay. Cytotoxicity was assessed in HSF cells. Stage-specific susceptibility assays were conducted using synchronized 3D7 parasites. Comparative docking analyses against β-hematin and the chloroquine resistance transporter (PfCRT), together with target prediction and molecular docking analyses, were performed to explore potential mechanisms. In vivo efficacy was evaluated using a Plasmodium yoelii 17XNL mouse model. Results: Fractionation yielded an active fraction (C2), and LC–HRMS and GNPS-based dereplication suggested a bile acid-like metabolite, with ursodeoxycholic acid (UDCA) returned as a putative spectral library candidate associated with fraction C2. Fraction C2 and UDCA showed comparable antiplasmodial activity against P. falciparum 3D7 (IC₅₀ = 6.55 ± 3.00 and 4.68 ± 0. 65 µg/mL, respectively) without detectable cytotoxicity up to 200 µg/mL. Activity was retained against multidrug-resistant K1 and Dd2 strains. Stage-specific assays demonstrated inhibitory activity across ring, trophozoite, and schizont stages without significant stage-dependent differences. Comparative docking analyses suggested interaction profiles distinct from chloroquine in β-hematin and PfCRT models. Additional docking analyses identified PfGluPho, PfMAPK, and PfPFT-β as potential targets. In vivo, UDCA reduced parasitemia in a dose-dependent manner without significant toxicity. Conclusions: UDCA exhibited moderate antiplasmodial activity across in vitro, in silico, and in vivo evaluations with a favorable selectivity profile, supporting further investigation of bile acid-like metabolites as potential antimalarial scaffolds. Full article

Ascophyllum nodosum extracts (ANE) are widely used biostimulants associated with improvements in plant growth, productivity, nutrient acquisition, and abiotic stress tolerance. However, the molecular mechanisms linking extract composition to plant signaling and physiological responses remain incompletely resolved. ANE contains a complex mixture of bioactive constituents, including polysaccharides, osmolytes, phenolic compounds, and phytohormone-like molecules. Their composition varies according to biomass source, environmental conditions, and extraction methodology, contributing to variability in biological activity. Current evidence suggests that ANE functions mainly as a signaling modulator rather than a direct nutrient source. ANE treatment has been associated with early cellular responses, including cytosolic Ca²⁺ influx, reactive oxygen species (ROS) generation, and mitogen-activated protein kinase (MAPK)-associated signaling events. However, many proposed mechanisms remain unresolved, and a considerable proportion of the available mechanistic evidence originates from studies using purified ANE-derived polysaccharides or related elicitor systems. ANE-associated responses include modulation of nutrient transport, primary metabolism, hormonal regulation, transcriptional reprogramming, and stress-responsive pathways, contributing to improved root development, nutrient acquisition, and defense-related responses. Nevertheless, limited knowledge of receptor-mediated perception mechanisms, signaling hierarchies, and extract-dependent variability continues to constrain mechanistic understanding and reproducibility. Future research should prioritize receptor identification, bioassay-guided fractionation, integrated multi-omics approaches, and improved standardization of extraction and formulation procedures. These advances will be essential for establishing robust mechanistic models and supporting the development of evidence-based ANE biostimulants for sustainable crop production. Full article

Reuse of human excreta and derivatives is becoming a common practice in areas with agricultural predominance. While in situ treated faeces through ecological sanitation (Ecosan), known as “faecal by-products” are being used to sustain soil nutrients and improve on-site sanitation, the concern remains about the health risks related to the survival of pathogens in these by-products in the community of farmers. This study assessed the survival of faecal pathogens and estimated microbial risks associated with the use of Ecosan faecal by-products in agriculture. The quantitative microbial risks assessment (QMRA) framework was used to estimate the risks posed by each faecal pathogen in solid and semi-solid faecal by-products under the probabilistic model of Monte Carlo simulation. Ascaris lumbricoides (6.5 eggs/gr), Taenia species (0.3 egg/gr), Schistosoma species (9.3 cercariae/gr), Entamoeba species (4.4 cysts/gr), and Escherichia coli (451 Cfu/gr) were detected in semi-solid faecal products. Exposure scenarios were observed throughout four critical points: vault faecal by-products removal/unloading, transport, collection, and application of faecal by-products in the gardens. Due to the presence of eggs and cysts, an estimated annual risk of infections was found in semi-solid faecal by-products with Schistosoma species (88%) and Ascaris lumbricoides (90%). Both concentrations were above World Health organisation (WHO) standards of associated infective risks of 0–10% of helminths in faecal sludge applied in the gardens. The users of faecal by-products, particularly farmers are exposed not only to high concentrations of helminth eggs but also to protozoa and bacteria with infective risks of Entamoeba species (99%) and E. coli species (62%). A stepwise implementation of faecal pathogens die-off during treatment of faecal by-products in compliance with the WHO’s 2018 guidelines can prevent the use of unsanitary faecal by-products. According to these findings, the proper control of intestinal protozoa and soil-transmitted helminths (STHs) should be enforced through personal protective measures in Burera district, Rwanda. Full article

The nucleation and growth mechanisms of copper electrodeposition from Cu(I)-containing-reline, a deep eutectic solvent, were investigated through a combination of electrochemical techniques and surface characterization. Cyclic voltammetry revealed the characteristic nucleation loop associated with an overpotential-driven electrocrystallization process, from which the equilibrium potential of the Cu(I)/Cu(0) redox couple was determined to be −0.35 V vs. a Ag quasi-reference electrode. Experimental potentiostatic current density transients were analyzed using nucleation models capable of accounting for both adsorption and three-dimensional (3D) diffusion-controlled growth, thereby allowing deconvolution of the individual contributions to the overall current response. The kinetic parameters, including the nucleation frequency and the number density of active sites, exhibited an exponential dependence on the applied overpotential, thus indicating enhanced nucleation kinetics at greater driving forces, while determining a Cu(I) diffusion coefficient of (3.39 + 0.09) × 10⁻⁷ cm² s⁻¹. Thermodynamic analysis showed that the Gibbs free energy of the formation of the critical nucleus decreases with increasing overpotential and follows the expected dependence on the inverse square of the overpotential, in agreement with classical nucleation theory. The estimated critical nucleus size was found to be smaller than one atom, suggesting that nucleation occurs at highly active surface sites. Furthermore, an exchange current density of (3 ± 1) μA cm⁻² was estimated for the Cu(I) electrochemical reduction. Scanning electron microscopy revealed a high density of copper nanoparticles (~20 nm) distributed across the electrode surface, along with larger aggregates (~100 nm) formed by coalescence and growth, consistent with a progressive nucleation mechanism. X-ray photoelectron spectroscopy confirmed that the deposits consist exclusively of metallic copper, with no evidence of oxidized species. These results demonstrate that copper electrodeposition in reline is governed by a complex interplay between the thermodynamic driving force, the interfacial kinetics, and mass transport, comprehensively providing fundamental insight into the electrocrystallization processes in deep eutectic solvents. Full article

This work presents a case study of sensitivity analysis applied to the modeling of ethanol steam reforming (SRE) in a catalytic porous medium, with a focus on hydrogen production. Considering the high variability of parameters reported in the literature, the objective is not to propose a universal model, but rather to assess the impact of uncertainties associated with input parameters on the model outcomes. The model was developed under steady-state conditions, coupling flow in porous media, species transport, and heat transfer, with kinetics described as a function of partial pressures. The sensitivity analysis was conducted through the systematic variation of kinetic and physicochemical parameters within ranges associated with their uncertainties. The results indicate that activation energy is the parameter most sensitive to uncertainty variation, exhibiting the greatest impact on hydrogen production. The thermal properties of the medium, particularly thermal conductivity and solid density, also stand out, highlighting the role of thermo-kinetic coupling. In contrast, parameters such as porosity, water reaction order, and particle diameter exhibited low sensitivity under the analyzed conditions. As a main contribution, this work establishes a sensitivity hierarchy associated with parameter uncertainties and provides guidance for other researchers regarding the prioritization of their determination and calibration in hydrogen production models. Full article

This meta-analysis combined the results of 61 independent studies published in 2005–2025 to examine polyamine-mediated responses to aluminum, cadmium, lead, chromium, copper, manganese, and selenium stress in plants. The logarithm ratio of responses (lnRR) under the random-effects model was used to calculate the effect sizes. Polyamine application significantly (p < 0.001) enhanced plant growth, with strong increases in root elongation (lnRR = 0.490, 95% CI: 0.362–0.618), fresh weight (lnRR = 0.413, 95% CI: 0.347–0.480), and dry weight (lnRR = 0.475, 95% CI: 0.409–0.541). Oxidative stress was markedly reduced, as reflected by decreases in reactive oxygen species accumulation (lnRR = −0.585, 95% CI −0.682 to −0.487, p < 0.001), hydrogen peroxide content (lnRR = 0.005, 95% CI −0.244 to 0.254, p = 0.968), and lipid peroxidation (lnRR = −0.487, 95% CI −0.578 to −0.397, p < 0.001). The antioxidant defenses were strengthened, and the levels of superoxide dismutase (lnRR = 0.468, p < 0.001) and catalase activity (lnRR = 0.373, p < 0.001) increased significantly. Metal accumulation was consistently reduced in polyamine-treated plants (lnRR = −0.392, 95% CI −0.460 to −0.324, p < 0.001). Supplementary genetic-level data indicated that metal stress triggers polyamines to regulate metal transporters, polyamine biosynthesis genes, antioxidant-related genes, and hormone-signaling pathways. Collectively, these data points make polyamines a key controller of plant metal stress tolerance and offer a quantitative and mechanistic system to apply them to metal-impacted agroecosystems. Full article

Hydrogen-rich shaft furnaces operated with coke oven gas (COG) represent an important low-carbon ironmaking route. Conventional porous-medium CFD models, however, do not explicitly resolve geometry-dependent burden descent or downward advection of solid sensible heat in variable-cross-section moving beds. To address this gap, a user-defined-scalar (UDS)-based pseudo-fluid moving-bed dual-temperature CFD framework is developed in this study. The framework couples geometry-dependent pseudo-solid kinematics, UDS-based transport of pseudo-solid species and sensible enthalpy, and a 12-step reduction-reforming-carbon reaction network on a fixed Eulerian mesh. It is applied to a 0.5 Mt·a⁻¹ industrial reactor through one reference case and three parametric groups covering solid descent velocity, cooling-side back pressure, and CH₄ content. Mesh-independence and mass-conservation checks indicate that the medium mesh is adequate for the intended trend-level assessment; the fine-to-medium deviations are 0.54% for DRI metallization, 0.23% for DRI outlet temperature, and 0.20% for top-gas temperature, with a net global mass residual of 1.53 × 10⁻⁶ kg·s⁻¹; the baseline DRI metallization (96.3%), carbon content (1.1%), and combined H₂ + CO utilization (29.45%) all fall within the reported ranges of the HBIS demonstration line and Energiron-ZR projects. As the descent velocity increases from 2.88 to 6.72 × 10⁻⁴ m·s⁻¹, DRI metallization drops from 98.0% to 79.4% and the outlet temperature rises from 313.3 to 719.4 K. Increasing the cooling-gas outlet back pressure from 60 to 100 kPa reduces the cooling-outlet excess flow from 1.49 to 0.11 kg·s⁻¹, indicating a dynamic gas-seal control between the two gas circuits, whereas raising the inlet CH₄ fraction from 10 to 23 vol% lowers the apparent CH₄ conversion from 29.5% to 18.5% and broadens the carbon-deposition zone. The framework offers a continuum basis for proof-of-concept and trend-level analysis of variable-cross-section hydrogen-rich moving-bed shaft furnaces. Full article

Folate is a central nutrient in one-carbon metabolism, contributing to nucleotide biosynthesis, methionine cycling, methyl-donor supply, and epigenetic regulation. In animals, the intestine is both a principal site of folate absorption and a key target organ for folate action. This narrative review focuses primarily on livestock, poultry, aquaculture species, ruminants, and animal-source food enrichment, while also using rodent, human, and in vitro studies as mechanistic or translational evidence. We synthesize evidence on folate absorption, transport, and metabolism and evaluate the mechanisms through which folate influences intestinal health. Available evidence suggests that adequate folate supply may support epithelial renewal, tight-junction integrity, mucosal immune balance, antioxidant capacity, gut microbiota stability, short-chain fatty acid production, and epigenetic regulation of intestinal development. These effects have been reported in poultry, pigs, fish, ruminants, rodents, and maternal–offspring models. However, the evidence is uneven across species, and dose–response relationships, folate forms, bioavailability, and species-specific requirements remain major limitations for translating current knowledge into animal production. Future studies should compare folic acid, 5-methyltetrahydrofolate, natural reduced folates, microbiota-derived folate, and folate-producing probiotics; quantify the contribution of microbiota-derived folate to host methyl-donor pools; and develop precision strategies that integrate folate with other one-carbon nutrients, probiotics, and product-enrichment technologies. Full article

The mitochondrial membrane protein UPS1, a conserved intermembrane space protein in Saccharomyces cerevisiae, possesses phosphatidic acid transfer activity and plays a positive regulatory role in processes such as cardiolipin metabolism and transport. The role of UPS1 protein in pathogenic fungi such as Candida albicans has not been explored, especially in relation to its influence on virulence factors like hyphal growth and biofilm formation, which are crucial for the pathogenicity of C. albicans. The research investigated the function of the UPS1 protein in C. albicans by using gene knockout techniques, analyzing mitochondrial function, and conducting tests for hyphal and biofilm development. The results revealed that deletion of the UPS1 gene leads to altered mitochondrial morphology, increased reactive oxygen species levels, and reduced intracellular ATP content, thereby causing severe growth defects in C. albicans. In addition, transcriptomic analysis indicated that loss of UPS1 significantly represses the expression of genes associated with hyphal growth and biofilm formation. Functional assays further confirmed that UPS1 deficiency markedly impairs cell adhesion capability, hyphal development, and biofilm formation of C. albicans. Notably, deletion of the UPS1 protein markedly reduces the susceptibility of C. albicans to membrane-targeted antifungal drugs. Finally, infection models using Galleria mellonella larvae and a murine vulvovaginal candidiasis model verified that UPS1 gene knockout attenuates the pathogenicity of C. albicans. In summary, our findings demonstrate that UPS1 protein modulates the pathogenicity of C. albicans by regulating mitochondrial function, hyphal growth, and biofilm formation. Full article

(1) Background: The rapid spatial expansion of the ruderal weed Chenopodium hybridum L. poses a potential challenge to agricultural production and regional ecosystems in China. However, the spatial evolution characteristics of its potential geographic distribution remain unclear under the compound scenarios of global warming and intensified human activities. (2) Methods: Utilizing an optimized MaxEnt model (regularization multiplier (RM) = 0.5, feature combination (FC) = LQ), this study integrated bioclimatic, topographic, soil, and Human Footprint (Hfp) data to predict the potential suitable habitats of C. hybridum in China under current conditions and four future Shared Socioeconomic Pathways (SSPs) emission scenarios (SSP126, SSP245, SSP370, and SSP585) for the 2050s and 2070s. Additionally, spatial turnover rate and centroid migration analyses were incorporated to elucidate its spatiotemporal dynamics. (3) Results: The results indicate that the optimized model exhibited robust predictive performance (Area Under the Curve (AUC) = 0.928). The Human Footprint (Hfp) was the environmental factor most prominently associated with the macro-spatial distribution of C. hybridum, with a relative contribution of 58.4%—significantly higher than any single natural geographic factor. Currently, potential suitable habitats are primarily concentrated in North, Central, and Southwest China, totaling approximately 205.59 × 10⁴ km². Under future climate scenarios, the highly suitable core habitats exhibit a consistent contraction trend, whereas the marginal suitable habitats shift spatially toward the arid inland regions of the northwest and the high-altitude areas of the southwest. By the 2070s under the higher-emission scenario (SSP585), the spatial turnover rate reaches a peak value (16.23%), and the distributional centroids of the potential suitable habitats exhibit localized directional shifts. (4) Conclusions: The spatial expansion trajectory of C. hybridum exhibits a high degree of spatial congruence with human activity corridors, reflecting a distinct macro-ecological niche spatial response characterized by shifts toward higher latitudes and elevations. It must be emphasized that the projections of this study reflect potential habitat suitability rather than definitive future actual distributions. The three-tier spatial management framework proposed herein—encompassing transport regulation, ecological management in core areas, and early warning in marginal zones—can serve as a scientific basis for the early monitoring and spatial management of this species under climate change. Full article

A new biomass pyrolyzer, named Biochar Oven, has been developed using flameless combustion technology, which provides uniform high temperature in the pyrolysis reactor. A computational fluid dynamics (CFD) model of flameless combustion was developed to analyze how the fuel inlet depth controls the reaction and heat transfer to a vertical biomass pyrolysis reactor. The combustor was modeled using the k–ε turbulence model, the discrete ordinates radiation model, and species transport with the reaction. The fuel nozzle relative depth ratios (RDR) of chamber height and equivalence ratios (ER) were varied to obtain optimal combustion and heat transfer performance. The internal recirculation ratio (Z) was calculated to evaluate the flameless combustion condition, with maximum values generally found at RDR 0.73 for each ER. Increasing depth strengthens the mixing zone closer to the reactor wall. With an ER of 0.9 and RDR of 0.73, the wall heat flux is up to 16.36 kW m⁻², the average wall reactor temperature is up to 900 °C, and the heat transfer efficiency is up to 59.79%. These flow patterns and chamber–reactor results indicate that deeper nozzle insertions (RDR 0.73) provide better overall performance by improving recirculation intensity, wall heat flux, and heat transfer efficiency with lower CO emissions. Full article

Environmental pollution has emerged as one of the most significant threats to human and ecosystem health, with growing evidence suggesting that chronic exposure to toxic substances may accelerate aging. The concept of gerontogens, toxic compounds capable of accelerating this biological process, has gained increasing attention in toxicological research, particularly in the context of global demographic shifts toward older populations. Current research on gerontogens relies heavily on invertebrate models with short lifespans, such as Caenorhabditis elegans, Drosophila melanogaster, and Saccharomyces cerevisiae, which are valuable for studying conserved mechanisms in aging pathways, but present significant limitations for translational accuracy to many aspects of vertebrate biology. Vertebrate models traditionally employed in toxicology, including mice and zebrafish, require substantially longer experimental timelines and higher financial investments, making lifetime exposure and aging assays particularly challenging. In this context, the turquoise killifish Nothobranchius furzeri emerges as a highly promising vertebrate model for aging toxicology research. Recognized as the shortest-lived vertebrate species maintained under laboratory conditions, N. furzeri reaches sexual maturity within 14 days and displays complete senescence by 4 months of age, at which point individuals are considered elderly, offering a decisive advantage over conventional vertebrate models. Furthermore, its capacity for embryonic diapause enables practical embryo storage, long-distance transport, and synchronized hatching, greatly facilitating experimental designs. Although N. furzeri is well established in gerontological research, with studies addressing hallmarks of aging such as telomere shortening, neurodegeneration, and cellular senescence, its application in ecotoxicology remains remarkably limited, with fewer than 10 published studies to date. This article argues that N. furzeri may represent a critical bridge between toxicology and aging research, offering an efficient and translationally relevant platform for investigating the effects of environmental contaminants on vertebrate aging. Current limitations of the model, such as lack of husbandry standardization, are also discussed. Expanding its use in this field holds considerable potential for advancing evidence-based strategies in public health and environmental conservation related to chronic exposure to contaminants. Full article

The accumulation of un-ionized ammonia (NH₃) during the transport of live ornamental fish poses a critical threat to animal welfare and post-transport survival. This study evaluated the efficacy of calcium alginate-encapsulated native Amazonian microalgae, Ankistrodesmus sp., Chlorella sp., Scenedesmus sp., and Synechococcus sp., for NH₃ bioremediation during a 15-day simulated transport of female Poecilia reticulata. Biometric endpoints were selected using a four-criterion framework, identifying specific growth rate by weight (SGRW), specific growth rate by length (SGRL), and Fulton’s condition factor (K) as essential non-redundant parameters. Time-weighted average (TWA) NH₃ served as the primary dose variable for four-parameter log-logistic modeling fitted to biological replicate means (n = 15). Ankistrodesmus sp. and Scenedesmus sp. maintained 97.8% survival and restricted TWA NH₃ to 0.036 and 0.047 mg/L, respectively, whereas the empty capsule control reached 6.7% survival and 0.150 mg/L TWA NH₃. Kruskal–Wallis tests on biological replicate means confirmed significant treatment effects on all biometric endpoints (SGRW: H(4) = 13.50, ε² = 0.950; SGRL: H(4) = 13.50, ε² = 0.95; p < 0.01). Chronic EC₅₀ values of 0.10505 mg/L NH₃ (SGRW; Adj-R² = 0.828) and 0.09967 mg/L NH₃ (SGRL; Adj-R² = 0.812) were established, representing approximately 7.8% and 7.4% of the female-specific acute LC₅₀ (1.34 mg/L NH₃), respectively, yielding chronic-to-acute ratios of approximately 13 for both growth endpoints and confirming that sublethal growth impairment precedes lethality. Partial disruption of the calcium alginate capsule matrix was observed from day 5 onward; the relative contributions of encapsulated and free-cell fractions were not quantified. Under the experimental conditions tested, 15-day simulated transport of female P. reticulata under controlled illumination and without feeding, calcium alginate-encapsulated Ankistrodesmus sp. and Scenedesmus sp. treatments represent effective, scalable, and residue-free alternatives to chemical ammonium neutralization for comparable ornamental fish transport scenarios; extension to dark commercial air transport or other species requires further experimental validation. Full article

Hypoxia-induced radioresistance remains a major obstacle in non-small cell lung cancer (NSCLC) radiotherapy. This study investigates whether artificially activating mitochondrial reverse electron transfer (RET) can enhance radiosensitivity in NSCLC by triggering oxidative stress. An in vitro hypoxia/reoxygenation (H/R) model was established in A549 cells to assess reactive oxygen species (ROS) levels, mitochondrial function, and metabolic alterations using fluorescence probes, flow cytometry, confocal microscopy, and targeted metabolomics. Mitochondrial complex inhibitors and dimethyl succinate (DM-S) were employed to validate the RET mechanism, and radiosensitivity was evaluated through clonogenic survival, apoptosis assays, and γ-H2AX staining. In vivo, A549 tumor-bearing mice received high oxygen (95% O₂) combined with DM-S and localized irradiation (4 Gy); tumor growth, histopathology, and immunohistochemistry were examined. H/R triggered substantial mitochondrial ROS production via complex I-mediated RET, dependent on a high mitochondrial membrane potential and electron transport chain imbalance, with succinate accumulation serving as a key metabolic switch. Exogenous DM-S exacerbated H/R-induced oxidative damage, DNA fragmentation (8-OHdG elevation, mtDNA integrity loss), and mitochondrial network disruption. H/R combined with DM-S significantly enhanced in vitro radiosensitivity, reducing clonogenic survival and increasing apoptosis to 53.4% ± 1.9% versus 10.3% ± 1.2% with irradiation alone. In vivo, the combination therapy markedly suppressed tumor growth, induced apoptosis and oxidative lipid damage (4-HNE), alleviated hypoxia (reduced HIF-1α), and showed no overt toxicity. These findings demonstrate that activating mitochondrial RET effectively enhances radiosensitivity in NSCLC. Succinate metabolism is a critical therapeutic target, and combining high oxygen with a succinate analog represents a promising radiosensitization strategy for hypoxic tumors. Full article