Search Results (443)

Polycyclic aromatic hydrocarbons (PAHs) are major toxic organic constituents attached to ambient fine particulate matter (PM2.5) and contribute substantially to PM2.5-associated oxidative stress and respiratory toxicity. This study investigated the protective effects of shallot (Allium ascalonicum) extracts against PAH-induced oxidative stress in human nasal epithelial cells (RPMI 2650). Shallot extracts were prepared using various extraction techniques and assessed for their phytochemical composition and antioxidant capacity. Among the extracts evaluated, the supercritical fluid extract exhibited the highest total flavonoid content and anti-inflammatory property, whereas the ethanolic extract (EtOH) exhibited the highest total phenolic content and antioxidant activity and was therefore selected for subsequent investigations. HPLC analysis of the EtOH extract identified quercetin and gallic acid as major phenolic constituents. Exposure of RPMI-2650 cells to PAHs (0.25 μg/mL) significantly induced intracellular reactive oxygen species (ROS) generation and lipid peroxidation while reducing superoxide dismutase (SOD) activity, indicating oxidative stress induction. Cotreatment with the ethanolic extract (1.25–5 μg/mL) effectively mitigated these effects by reducing ROS generation, suppressing lipid peroxidation, and restoring SOD activity in a dose-dependent manner. These protective effects are attributed to the antioxidant phytochemicals present in shallot, particularly quercetin. Collectively, these findings indicate that shallot extracts attenuate PAH-induced oxidative stress in human nasal epithelial cells. Full article

The expansion of the European Union Emissions Trading System to road transport and buildings (ETS2) raises significant concerns regarding the distributive social impacts of carbon pricing on vulnerable households, particularly in regions characterized by high car dependency, limited public transport accessibility, and pronounced territorial inequalities. This paper aims to develop an integrated conceptual framework for analyzing transport poverty in the context of ETS2 and the just climate transition. The study adopts a conceptual–analytical approach based on a structured literature review of peer-reviewed publications and EU policy documents, combined with a qualitative policy analysis focused on Bulgaria as a critical case. The paper identifies six interacting analytical dimensions of transport poverty—economic vulnerability, spatial vulnerability, mobility dependency, infrastructure vulnerability, climate-policy exposure, and social vulnerability—and maps the causal pathways through which carbon pricing mechanisms may intensify mobility deprivation, particularly among low-income, rural, and forced-car-ownership households. The analysis demonstrates that ETS2 may exacerbate existing socio-spatial inequalities unless accompanied by well-designed compensatory, accessibility-oriented, and territorially sensitive policy measures. The Bulgarian case illustrates the specific structural risk factors prevalent in Central and Eastern European countries. The paper contributes to the emerging academic literature on transport poverty by positioning it as a critical dimension of the just climate transition and by providing a conceptual foundation for future empirical research within the ACTETS2 project framework. Full article

The extension of the European Union Emissions Trading System to buildings and road transport (ETS2) raises important questions about the distribution of carbon pricing burdens across Member States. While existing research has primarily focused on income differences or household typologies, the structural heterogeneity of vulnerability across EU countries remains insufficiently explored. This study develops a dual-channel framework of household vulnerability to ETS2, distinguishing between structural carbon exposure and socio-economic sensitivity. Using a balanced panel of 27 EU Member States over 2010–2024, we construct composite indices based on Eurostat data and combine cluster analysis, sigma-convergence tests, and two-way fixed-effects models with Driscoll–Kraay standard errors. The results suggest that the two vulnerability channels are empirically distinct and geographically differentiated across Member States, with no country group simultaneously characterized by high exposure and high sensitivity. Energy productivity and renewable energy expansion are associated with lower structural exposure but higher socio-economic sensitivity, consistent with a transitional burden mechanism. Over time, composite vulnerability exhibits statistically significant divergence, despite partial and uneven convergence across the underlying vulnerability dimensions. These findings highlight the need for differentiated compensation mechanisms and structural policy interventions that address both structural exposure and socio-economic sensitivity, supporting a socially equitable and sustainable energy transition under ETS2. Full article

Background and Aims: Type 2 diabetes mellitus is a recognized risk factor for hepatocellular carcinoma (HCC), particularly in the setting of metabolic dysfunction-associated steatotic liver disease (MASLD), chronic viral hepatitis, advanced fibrosis, and cirrhosis. Beyond hyperglycemia and insulin resistance, diabetic hepatocarcinogenesis is shaped by metabolic inflammation, lipotoxicity, oxidative stress, fibrogenic remodeling, and the cirrhosis-dysplasia-HCC continuum. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) may influence several hepatometabolic pathways, but the epidemiologic evidence linking SGLT2i use to HCC risk remains heterogeneous. Methods: We conducted a systematic review and meta-analysis of observational studies evaluating SGLT2i exposure and incident HCC in adults with type 2 diabetes. PubMed, Embase, and the Cochrane Library were searched up to 15 March 2026. Adjusted time-to-event estimates were pooled using a restricted maximum likelihood (REML) random-effects model. The certainty of evidence was assessed using the GRADE framework and judged to be very low. Results: Six observational studies including 526,446 participants were included. SGLT2i exposure was associated with a lower observed risk of incident HCC (pooled HR 0.59, 95% CI 0.45–0.77), but between-study heterogeneity was substantial (I² = 75.2%, τ² = 0.074). The association remained directionally similar after exclusion of Huynh et al. (HR 0.61, 95% CI 0.45–0.81) and in a DPP-4 inhibitor-restricted active-comparator analysis (HR 0.60, 95% CI 0.39–0.92). However, the 95% prediction interval crossed the null (0.25–1.37), indicating that future comparable studies may plausibly show no protective association. Conclusions: SGLT2i exposure was associated with a lower observed risk of incident HCC across available observational studies. However, the certainty of evidence was judged to be very low, and substantial heterogeneity, comparator variation, mixed time-to-event estimands, residual confounding, and a prediction interval crossing the null preclude causal interpretation. These findings should be considered hypothesis-generating rather than practice-changing evidence and support further hepatology-oriented validation. Full article

Herbicides, used worldwide to improve agricultural yields, are associated with pollution and significant health problems. Cardiac damage is a major concern, and the respective contributions of glyphosate (GP) and its commercial formulation, Roundup^® (RU), warrant investigation. We studied the specific effects of GP and RU on isolated rat cardiac mitochondria and on H9c2 cardiomyocytes cultured for 6 and 24 h to determine whether the potential cardiotoxicity of GP and/or RU are linked to impaired mitochondrial respiration and increased hydrogen peroxide (H₂O₂) production. To this end, we used various mitochondrial complex substrates and a high-resolution oxygraphy. Unlike the GP alone which demonstrated no significant effect, the RU decreased cardiac mitochondrial respiration (21.90 ± 2.99 vs. 41.23 ± 7.09 pmol/s/mL, −46.9%, p = 0.007) for OXPHOS CI in respectively the RU and the control groups. RU also impaired OXPHOS CI+II (−51.5%, p = 0.003), maximal mitochondrial respiration (ETS CI+II, −46.7%, p = 0.001) and coupling (−35.4%, p = 0.0003). Similarly, 24 h exposure to RU decreased H9c2 cell number (−48.59%, p = 0.0023) but increased their mitochondrial respiration (+38.2%, p = 0.03, +37.6%, p = 0.03, +43.2%, p = 0.03 for OXPHOS CI, OXPHOS CI+II and ETS CI+II respectively). We observed a similar trend (NS) after 24 h exposure to GP. In conclusion, these results support an enhanced cardiac toxicity of the Roundup^® as compared to the glyphosate. Both decreased mitochondrial respiration and increased hydrogen peroxide production were involved in isolated mitochondria impairment. After 24 h exposure to Roundup^®, a compensatory mechanism potentially counterbalanced the decreased H9c2 cell number. These data support future studies aiming to reduce Roundup^®-associated cardiac alterations not only by reducing its use but also by investigating the effectiveness of antioxidant and mitochondria-focused therapy. Full article

The study compares the effects of the HSP60-derived mutated peptide (CIGB-258) and its wild-type peptide (E18-3) on preventing carboxymethyllysine (CML)- and ethanol (Et-OH)-induced hemorrhagic events and acute toxicity in zebrafish. The results suggest a 67% survivability and swimming recovery in CIGB-258-treated zebrafish compared to only 20% in the CML+Et-OH-treated group. No effect of E18-3 was noticed on CML+Et-OH-impaired zebrafish survivability and swimming ability. Similarly, no effect of E18-3 was noticed on the CML+Et-OH-disturbed blood oxidative and antioxidant variables. In contrast, CIGB-258 showed a notable 35% lower rate of oxidized contents, and 2.0-fold and 1.2-fold higher paraoxonase (PON) and ferric ion reduction activity (FRA), respectively, than in the E18-3 group. Also, the CML+Et-OH-induced dyslipidemia was substantially prevented by the CIGB-258, whereas no protective effect of E18-3 was noticed. Similarly, the CML+Et-OH-triggered hepatic inflammation, steatosis, kidney damage, severe gastrointestinal bleeding, and intestinal fibrosis were successfully mitigated by co-treatment with CIGB-258. Surface plasmon resonance analysis revealed a substantial binding affinity of CIGB-258 for HDL₂ and HDL₃, characterized by association rate constants (K_a) of 14.78 and 6.20 μM⁻¹s⁻¹, dissociation rate constants (K_d) of 0.35 s⁻¹ and 0.22 s⁻¹, and equilibrium dissociation constants (K_D) of 0.024 and 0.035 μM, respectively. In conclusion, CIGB-258 exerted a substantial impact on CML+Et-OH-triggered adverse events, with high affinity for HDL, whereas E18-3 exposure remained unaffected and failed to produce any beneficial effects. Full article

Prenatal alcohol exposure (PAE) is a major public health concern, yet maternal self-reporting remains unreliable. Meconium accumulates alcohol metabolites during the second half of gestation, and ethyl glucuronide (EtG) is considered a stable and specific biomarker of late-pregnancy alcohol exposure. Diapers containing meconium may serve as a noninvasive method for collecting anonymous biological samples, which could help reduce participation bias in studies of this sensitive subject. This pilot study assessed the feasibility of anonymously collecting meconium-containing diapers for subsequent quantitative EtG analysis after extended periods of frozen storage and international transport, and examined intra-pair consistency in samples from the same newborn. Mothers collected their newborns’ diapers, which were then divided into two aliquots (A and B) by a study assistant and stored at −80 °C until analysis. Out of 178 samples collected from 105 infants, 137 samples were analyzable. Eleven samples exceeded the limit of quantification (10 ng/g), while two samples (one pair) surpassed the 30 ng/g cutoff, indicating significant PAE. EtG concentrations showed high intra-pair agreement, supporting the robustness of the biomarker and analytical method. Anonymous diaper-based meconium collection is feasible but operationally demanding. Although the low participation rate and methodological factors, including sample loss, precluded true prevalence estimation, making it exploratory, the detection of quantifiable EtG in 8% of analyzable samples suggests that PAE remains an issue. Full article

Background/Objectives: Chronic ethanol (EtOH) consumption is a major cause of metabolic dysfunction and multi-organ injury, particularly in the liver and pancreas. Because oxidative stress and endoplasmic reticulum (ER) stress are central mechanisms in both organs, this study evaluated the protective efficacy of 4-hexylresorcinol (4HR) against EtOH-induced hepato-pancreatic injury. Methods: Male C57BL/6J mice (6 weeks old) were assigned to four groups (n = 10/group): control, EtOH, EtOH + 4HR (5 mg/kg), and EtOH + 4HR (10 mg/kg). After a 1-week adaptation period, mice were fed a liquid EtOH diet for 5 weeks. Glucose tolerance, fasting glucose, serum insulin, and insulinogenic index were assessed. Liver and pancreas were analyzed by histology, immunohistochemistry, Western blotting, periodic acid-Schiff staining, Oil Red O staining, and malondialdehyde assay. Results: Chronic EtOH exposure impaired glucose homeostasis, reduced the insulinogenic index, increased hepatic inflammation and ALT levels, depleted hepatic glycogen, elevated pancreatic lipid peroxidation, and upregulated GADD153 (CHOP) expression in both the liver and pancreas. 4HR administration, particularly at 10 mg/kg, attenuated several of these alterations. 4HR treatment was associated with reduced hepatic inflammatory changes and ALT elevation, decreased pancreatic malondialdehyde levels, and suppressed GADD153 expression in both organs. Although PAS staining in the 4HR-treated group showed a qualitative tendency toward increased hepatic glycogen deposition, quantitative analysis did not demonstrate significant recovery relative to the EtOH group. Conclusions: 4HR showed protective effects against several aspects of chronic EtOH-induced hepatic and pancreatic injury, including hepatic inflammation, pancreatic lipid peroxidation, and ER stress-related GADD153 expression. However, quantitative PAS analysis did not support significant restoration of EtOH-induced hepatic glycogen depletion by 4HR. These findings suggest that 4HR may serve as a potential multi-organ protective agent against alcohol-induced inflammatory, oxidative stress-, and ER stress-related injury, although its effect on hepatic glycogen metabolism remains limited under the present experimental conditions. Full article

Background: Prenatal alcohol exposure (PAE) is a major preventable cause of neurodevelopmental impairment. Little is known about its impact on real-life child/adolescent academic outcomes, which are key functional indicators of long-term social participation. Methods: PAE was assessed in a sample of 156 participants via (1) meconium ethyl glucuronide (EtG) concentration (≥10 ng/g; EtG-positive, n = 36) and (2) third-trimester maternal self-report (SR-positive, n = 40). At primary school (6–10 years, t1) and secondary school ages (12–14 years, t2), exposed and non-exposed children were compared regarding primary school grades (t1) and secondary track placement (t2). Results: At t1, EtG-positive children exhibited lower school report grades by trend (n = 15, p = 0.068–0.085) with a moderate effect size (r = 0.36–0.39). SR-positive children demonstrated significantly lower school report grades (n = 15, p = 0.016) with strong effect (r = 0.56). At t2, both exposure groups had increased trend-significant odds of attending lower educational tracks (EtG-positive/-negative: n = 153, OR = 1.84, p = 0.059; SR-positive/-negative: n = 153, OR = 1.78, p = 0.066). Conclusions: PAE is associated with reduced real-life academic outcomes across development. School performance represents a sensitive functional outcome of neurodevelopmental vulnerability following PAE. Meconium EtG may contribute to postnatal identification of affected children. Full article

This study examines corporate carbon emissions of Korean firms from an ESG perspective and develops an AI-based screening framework to improve the identification of firms likely to exceed regulatory emission thresholds. As global climate policies and carbon pricing mechanisms expand, understanding the emission profiles of listed companies has become increasingly important for regulators, investors, and policymakers. Despite growing ESG disclosure, reliable firm-level screening tools for carbon emissions remain limited. Using a pooled annual panel of KOSPI-listed non-financial firms from 2019 to 2024, the study constructs a dataset of 552 firm-year observations. Firms are classified as high-emission when annual emissions exceed the Korean Emissions Trading Scheme (K-ETS) regulatory threshold of 125,000 tCO₂e. To evaluate predictive performance, the analysis compares multiple machine learning models (RF, SVM, XGBoost, LightGBM, and CatBoost) and deep learning models (CNN, RNN, GAN, LSTM, and Transformer). In addition, a hybrid ensemble combining CatBoost, GAN, and Transformer is proposed to enhance predictive reliability. The empirical results show that ESG-augmented models consistently outperform financial-only baselines across AUC and F1 metrics. Among individual models, the ESG-enhanced Transformer achieves the strongest discriminatory power, while the proposed hybrid ensemble delivers the best overall predictive performance. The findings contribute to the literature by demonstrating the incremental value of ESG information in predicting corporate carbon emissions and by presenting a practical AI-based framework for compliance-oriented screening under carbon regulation. From a policy and investment perspective, the model provides a useful decision support tool for anticipating potential inclusion in emissions trading schemes, assessing transition exposure, and supporting data-driven decarbonization strategies. Full article

The residual mechanical properties after fire exposure form the basis for evaluating the structural performance of aluminium alloy components subjected to fire without collapse. This research investigated the impact of low cooling rates on the residual mechanical properties of 6063-T5 aluminium alloy after various cooling methods were utilized. A total of 48 tensile specimens were subjected to controlled elevated temperatures (ETs) ranging from 200 to 500 °C for 30 min soaking, followed by two cooling regimes: cooling in air (CIA) and cooling in furnace (CIF). For both CIA and CIF conditions, an increase in ETs led to a gradual increase in ductility, particularly elongation at fracture. Moreover, the effects of ETs on the fracture performance were discussed. Key mechanical parameters—namely nominal yield strength, ultimate tensile strength, elastic modulus, and strain at ultimate strength—were quantified across ETs and cooling methods, which were compared among different aluminium alloys. Empirical predictive equations were developed to capture the temperature-dependent degradation trends of mechanical properties, and a plasticity Ramberg–Osgood model was proposed and validated against test data. The metallographic microstructure of 6063-T5 aluminium alloy after different ETs revealed that the evolution of precipitate was the primary contributor to strength degradation. Finally, finite element simulations of aluminium plate girders after various ETs were conducted, which incorporated the proposed constitutive model and replicated the degradation trends observed in tensile tests. These findings provide a reliable foundation for implementing the proposed model into finite element simulations and structural assessment tools for post-fire aluminium alloy structures. Full article

Cancer progression is influenced by the dynamic interplay between tumor cells and the surrounding stromal microenvironment. Therapy-induced senescence (TIS) of stromal fibroblasts represents a common outcome of anticancer treatments, contributing to tumor progression through the senescence-associated secretory phenotype (SASP). While SASP cytokines promote cancer malignancy, the contribution of secreted metabolites from senescent cells remains poorly understood. Here, we investigate the role of senescent stromal metabolism in regulating prostate and ovarian cancer cell invasion. Conditioned media (CM) from TIS-induced human prostate (HPFs) and ovarian fibroblasts (HOFs) promote enhanced invasion of cancer cells. Invasion is partially preserved after exposure to boiled CM, suggesting a role for heat-stable metabolic factors. Metabolomic profiling of senescent fibroblasts-derived CM reveals a significant increase in Glutamine (Gln) levels, identifying senescent stromal fibroblasts as a previously unrecognized source of extracellular Gln in the tumor microenvironment (TME). Exposure of cancer cells to senescent CM increases Gln uptake, together with upregulation of the transporter SLC1A5 and increased intracellular Gln. This metabolic adaptation is associated with increased malignant phenotype including epithelial-to-mesenchymal transition (EMT) and stemness features. Extracellular Gln depletion, pharmacological inhibition of glutaminase-1 (GLS1) in cancer cells, or Gln synthetase (GS) silencing in fibroblasts markedly impair senescent fibroblasts CM-induced invasion, EMT markers expression, and stemness features in cancer cells. Stromal-derived Gln is associated with increased cancer cell invasion through activation of a redox-dependent NRF2/ETS1 signaling axis. Analysis of patient-derived transcriptomic datasets further suggests chemotherapy-associated upregulation of Gln metabolism and ETS1 expression. These findings identify senescent stromal-derived Gln as a key metabolic driver of prostate and ovarian cancer aggressiveness and reveal a TIS-associated metabolic vulnerability that could be explored in future preclinical studies. Full article

Coastal ecosystems are increasingly threatened by climate change, especially the rising frequency of marine heatwaves (MHWs), which often co-occur with emerging nanomaterials such as graphene oxide (GO), whose ecological risks are still being evaluated. While the effects of GO have been studied in isolation, little is known about its interaction with thermal stress events. This research studied the combined effects of temperature (18 °C and 23 °C, simulating control and MHW conditions) and GO nanosheets exposure (0.01 mg/L) on two key estuarine bivalves: the clam Scrobicularia plana and the mussel Mytilus galloprovincialis. After 7 days of exposure (duration of many MHWs), energy metabolism, antioxidant defenses, oxidative damage, and neurotransmission were assessed. The results revealed that clams exhibited lower ETS and SOD activity when exposed to MHWs and lower SOD and AChE activities at MHW + GO, compared to the control treatment. Mussels relied primarily on SOD activity across treatments but showed increased susceptibility to GO nanosheets, with higher LPO levels and a significant reduction in AChE activity when exposed to GO at both temperatures. Overall, our findings suggest that S. plana shows a stronger response to the environmental alterations tested than M. galloprovincialis. Combined exposure to GO + MHW triggers species-specific biochemical responses in estuarine bivalves, highlighting how physiological traits shape the assessment of ecological risks posed by nanomaterial pollution under climate change. Full article