Search Results (4,612)

Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants increasingly linked to male reproductive toxicity; however, the molecular mechanisms underlying testicular damage remain unclear. This study evaluated PS-NP-associated testicular damage in rats after 55 days of exposure and assessed the modulatory effects of Nelumbo nucifera leaf, flower, and rhizome extracts, with quercetin as a reference. PS-NP exposure reduced spermatogenic cell populations, testicular, epididymal weights, and sperm motility. These changes were accompanied by increased NOX4 and NF-κB expression, upregulation of intrinsic apoptosis-related genes (Tp53, Bax, Caspase-9, and Caspase-3), elevated caspase-3 and caspase-9 protein levels, and enhanced cleaved caspase-3 immunoreactivity. In contrast, Fas and Caspase-8 were downregulated, confirming intrinsic mitochondrial apoptosis. PS-NP exposure also altered reproductive hormone receptor expression (LHr, FSHr, and AR) and dysregulated chromatin-regulatory genes, with increased Dnmt1, Dnmt3a, and Ehmt2 (G9a) and decreased Hdac1 and Ep300. Co-administration of N. nucifera attenuated most of these alterations, with the rhizome extract exhibiting the most pronounced protective effect. GO and PPI network analyses suggested functional connectivity among stress-responsive, apoptotic, and chromatin-modifying proteins. Docking simulations indicated phytochemical-apoptosis-related protein interactions. PS-NPs may impair testicular homeostasis through coordinated stress, apoptosis, endocrine disturbance, and epigenetic dysregulation, with possible relevance to male reproductive health, while N. nucifera shows promise as a protective modulator. Full article

Proteasome inhibitors (PIs) are central to multiple myeloma (MM) therapy; however, resistance remains a major clinical challenge, particularly in relapsed/refractory disease. To identify functional mediators of carfilzomib (CFZ) resistance, we performed complementary gain-of-function CRISPR activation and pharmacological screening approaches. These unbiased strategies converged on the E3 ubiquitin ligase MDM2 as a modulator of PI response. MDM2 transactivation enhanced MM cell survival and accelerated recovery following CFZ exposure, supporting a causal role in proteotoxic stress tolerance. Pharmacologic inhibition of MDM2 with NVP-CGM097 synergized with CFZ across multiple PI-sensitive and PI-resistant MM cell lines, irrespective of TP53 status. Mechanistically, MDM2 inhibition induced p21 upregulation, cell-cycle arrest, and reduced c-MYC expression, accompanied by impaired activation of DNA damage response mediators. Genetic silencing of MDM2 phenocopied these effects and increased CFZ sensitivity. Importantly, the combination retained efficacy in MM–stromal co-culture models and in primary patient samples, including cases harboring del(17p), while sparing normal peripheral blood mononuclear cells. Collectively, these findings identify MDM2 as a functional driver of PI resistance and support combined MDM2 and proteasome inhibition as a rational therapeutic strategy in MM, including TP53-deficient contexts. Full article

Aerobic exercise capacity, best quantified by maximal oxygen uptake (VO_2max), varies between individuals and is dependent on cardiac output (CO) and oxygen uptake in the periphery (a-vO₂ diff). Environmental stressors like hypoxia, microgravity, and heat negatively impact these parameters, thereby reducing aerobic exercise capacity. However, in response to acute and chronic exposures to these environments, compensatory processes serve to counteract reductions in VO_2max. In hypoxic environments, reduced oxygen partial pressure (PO₂) leads to hypoxic pulmonary vasoconstriction (HPV) and a diffusion limitation at the level of the lungs and skeletal muscle, resulting in a reduction in VO_2max. Microgravity environments reduce VO_2max through cardiac and skeletal muscle deconditioning, as well as reductions in plasma volume (PV), resulting in an increase in sympathetic nerve activity through baroreceptor-mediated pathways. In heat stress environments, increases in skin perfusion upon acute exposure hinder exercise performance, whereas compensatory PV expansion mitigates further decreases in VO_2max. As humans are increasingly exposed to austere environments and environmental extremes, it is critical to understand how these environments impact cardiovascular exercise physiology so that effective strategies and protocols ensuring proper aerobic functioning may be implemented. Full article

Concurrent alcohol and cannabis use (“crossfading”) is increasingly prevalent, especially among adolescents, yet its toxicological impact on pulmonary innate immunity remains largely unexplored. Alveolar macrophages (AMs) orchestrate inflammatory responses in the lung, and dysregulated macrophage polarization is a hallmark of alcohol-associated lung disease. Although alcohol and cannabinoids individually modulate immune function, the mechanisms by which their co-exposure alters macrophage activation and inflammatory signaling in the lung are largely unknown. AMs are highly sensitive to xenobiotic exposure and play a central role in regulating inflammatory and cytotoxic responses. In this study, we investigated how acute ethanol exposure, synthetic cannabinoid exposure, and their combined exposure affect macrophage viability, polarization, and the release of inflammatory mediators via cannabinoid receptor (CB1R/CB2R)-dependent pathways. Human THP-1-derived macrophages and KG-1 macrophage-like cells were exposed to ethanol, the CB1/CB2 agonist WIN 55,212-2, or both, with selective pharmacological antagonism of CB1R and CB2R. Ethanol exposure activated and polarized macrophages toward a pro-inflammatory M1 phenotype, accompanied by increased secretion of pro-inflammatory cytokines MCP-1, TGF-α, IFN-β, IL-6, and TNF-α. In contrast, WIN 55,212-2 promoted anti-inflammatory M2 polarization and increased IL-10 and IL-4 production. Notably, co-exposure to ethanol and WIN produced an antagonistic immunomodulatory response, characterized by the suppression of ethanol-induced M1 polarization and attenuation of pro-inflammatory cytokine release. Mechanistically, pharmacological CB1R blockade reduced ethanol-induced M1 polarization and cytokine secretion, whereas CB2R blockade exacerbated these effects, underscoring divergent roles for cannabinoid receptors in regulating pulmonary macrophage responses. This study provides novel findings demonstrating the mechanism by which alcohol–cannabinoid co-use reshapes macrophage immune phenotypes and identifies the endocannabinoid system as a potential therapeutic target for alcohol-related inflammatory lung disease. Full article

The overuse of antibiotics has led to their widespread environmental residues, posing a significant threat to the ecological environment. In this study, a flower-like spherical CoFe-layered double hydroxide (CoFe-LDH) catalyst was prepared using a hydrothermal method. The degradation performance of the CoFe-LDH/peroxymonosulfate (PMS) system was systematically investigated using tetracycline (TC) as a model pollutant. The CoFe-LDH exhibited a three-dimensional nanoflower-like spherical structure formed by interlaced nanosheets, featuring smooth surfaces and well-defined edges. This hierarchical porous structure facilitates the exposure of active sites. The CoFe-LDH/PMS system demonstrated remarkable degradation efficiency, achieving over 90.17% TC removal within 10 min. As the dosage of CoFe-LDH and PMS increases, the degradation rate of TC improves significantly, but the marginal improvement effect decreases. TC degradation efficiency increased with pH up to an optimum at pH 5.0, beyond which it declined. The anions—Cl⁻, $\mathrm{N}{\mathrm{O}}_3^{-}$, and $\mathrm{S}{\mathrm{O}}_4^{2-}$—all exhibited inhibitory effects on TC degradation; the TC removal rates decreased to 77.88%, 80.58%, and 82.78%, respectively. The removal experiments of different organic pollutants, such as oxytetracycline (88.91%), methylene blue (98.36%), and ciprofloxacin (84.52%), as well as actual water experiments, such as lake water (92.48%) and tap water (80.86%), have demonstrated the good universality of the CoFe-LDH/PMS system. Radical quenching experiments confirmed that ^•OH and $\mathrm{S}{\mathrm{O}}_4^{\text{•}-}$ were the dominant reactive species. Full article

The indoor microclimate of museums plays an essential role in preserving priceless cultural heritage for future generations and in ensuring visitors’ comfort and health. In this context, the present study aimed to evaluate indoor air quality, the degree of fungal contamination, and visitors’ perceptions in a museum environment through an integrated, interdependent approach. Measurements of the physicochemical parameters of air quality (temperature, relative humidity, CO₂, TVOC, HCHO, PM_2.5 and PM₁₀, negative and positive ions and brightness) were carried out in three exhibition halls within a museum in Oradea, Romania, during the period January–August 2024. Fungal contamination was assessed using surface and air samples, with classical isolation and microscopic identification methods. Visitors’ perceptions were analysed using a standardised questionnaire that focused on perceived comfort and visit duration. The results showed that the parameters defining indoor air quality generally fell within the limits set by the international standards in force, with occasional exceedances. These conditions are associated with the presence of fungi of the genera Cladosporium, Penicillium, and Aspergillus in the air and on museum exhibits, which pose risks to human health and the deterioration of the exhibited materials. The statistical decision-making model determined the critical thresholds above which visitor behaviour changed visibly. The results highlighted the importance of maintaining a stable microclimate in museum spaces, not only for the protection of exhibits, but also for optimising the cultural experience. Indoor air quality indicators and fungal microflora can only affect vulnerable people or those with pre-existing conditions. Occasional visitors do not present a significant risk of developing new conditions, considering the limited duration of exposure. Full article

This study evaluated the protective effects of green coffee (Coffea arabica L.) extract (GCE) against metabolic and endocrine disturbances induced by fipronil (FIP) in male rats. Animals were randomly allocated into four groups (n = 6): control, GCE (100 mg/kg), FIP (4.85 mg/kg), and combined FIP + GCE, and treated orally for 90 days. FIP exposure significantly impaired glucose homeostasis, as indicated by a 14.8% increase in the oral glucose tolerance test (OGTT) response and a 2.4-fold increase in the homeostatic model assessment of insulin resistance (HOMA-IR). It also disrupted lipid metabolism, with marked elevations in triglycerides (74.10%) and total cholesterol (57.55%). Endocrine imbalance was evident, including increased resistin levels (113.86%) and reduced triiodothyronine (T3; −37.5%), adiponectin (−42.73%), and high-density lipoprotein (HDL; −9.31%). Oxidative stress and inflammation were significantly enhanced, as demonstrated by elevated malondialdehyde (MDA; +93.56%) and pro-inflammatory cytokines (IL-1β: +246.56%; IL-6: +275%), alongside a reduction in total antioxidant capacity (TAC; −45.24%). Additionally, serum albumin levels decreased markedly (−54%). Co-administration of GCE significantly improved metabolic, hormonal, and inflammatory parameters, including insulin resistance (HOMA-IR). Histopathological analysis further confirmed its protective effects on hepatic and renal tissues. Overall, GCE mitigates FIP-induced metabolic and endocrine dysfunction, likely through its antioxidant and anti-inflammatory properties. Full article

The redclaw crayfish (Cherax quadricarinatus) features a unique intersex phenotype—functional males harboring a female (ZW) genotype. This study investigates the sexually dimorphic transcriptomic responses of the hepatopancreas to acute methyl farnesoate exposure to decouple genotypic from phenotypic sex. We found that normal males prioritize enzymatic detoxification and steroidogenesis, whereas normal females prioritize energy conservation for reproductive preparation. Strikingly, intersex individuals exhibited a massive transcriptomic burst and paradoxical hormone receptor dynamics, exposing a fragile endocrine network driven by their inherent genotypic–phenotypic conflict. To survive severe MF-induced pharmacological stress, the intersex hepatopancreas actively suppresses lysosomal and apoptotic pathways, which we hypothesize serves as a compensatory mechanism to mitigate severe tissue damage. Instead, it deploys a compensatory architecture by hyperactivating amino acid biosynthesis, sulfur relay systems, and gap junctions to manage proteotoxic and oxidative stress. Co-expression network analysis identified VCP, maf, and hdac8 as central regulatory hubs orchestrating this survival strategy through proteostasis, oxidative sensing, and epigenetic override. These findings suggest that the crustacean response to acute pharmacological challenge involves profound metabolic and epigenetic reprogramming, providing novel hypotheses for future functional studies. Full article

Air pollution is a growing hazard to global health. Epidemiological studies have reported a potential role of air pollutant exposure in the development or aggravation of neurodegenerative diseases. However, the underlying mechanisms are ill-defined. Ferroptosis is an iron- and reactive oxygen species (ROS)-dependent form of cell death that drives neuronal loss in neurodegenerative diseases. Our previous studies reported the involvement of adenosine 3′,5′-cyclic monophosphate (cAMP) and EPAC (exchange protein directly activated by cAMP) in ferroptotic cell death. Here, we investigated the effects of diesel exhaust particles (DEP) in mouse hippocampal (HT22) neuronal cells. Our data showed that toxicity induced by RSL3 (50–75 nM), a ferroptosis inducer, was significantly increased by the addition of DEP (100 μg/mL). Pharmacological inhibition of EPAC1 (CE3F4 30 μM or AM-001 30 μM) and soluble adenylyl cyclase (sAC; TDI-10229 1 μM or TDI-11861 0.1 μM) prevented enhanced ferroptotic HT22 cell death caused by DEP, while pharmacological modulation of EPAC2, protein kinase A (PKA), phosphodiesterases (PDEs), or transmembrane AC did not. DEP in combination with RSL3 exposure increased intracellular calcium levels and induced lysosomal de-acidification. Furthermore, inhibition of EPAC1 prevented mitochondrial ROS (MitoSOX) and lipid peroxidation (BODIPY C11 and MDA levels) after DEP and RSL3 co-exposure. Collectively, EPAC1 may serve as a novel target for the treatment or prevention of neurodegenerative diseases accelerated by air pollution. Full article

Background/Objectives: The emergence of SARS-CoV-2 variants and breakthrough infections underscores the need for next-generation vaccines capable of protecting from natural infection and/or preventing virus transmission. Intranasal vaccination offers a promising approach by eliciting local immune responses in the nasal mucosa, the primary site of infection and reservoir for transmissible virus. We evaluated two live-attenuated, respiratory syncytial virus-vectored vaccines in which the RSV F and G surface glycoproteins were replaced with a chimeric SARS-CoV-2 Spike protein from the ancestral USA/WA-1/2020 strain (MV-014-212) or the Delta variant (MV-014-212-delta). Methods: K18-hACE2 mice and LVG Syrian hamsters were vaccinated with a single intranasal dose of MV-014-212 or MV-014-212-delta. Systemic and mucosal immunity were assessed following vaccination, and protection was evaluated following Delta SARS-CoV-2 challenge. In vaccinated hamsters, morbidity, viral shedding, and lung inflammation and injury were also assessed following natural exposure to infected cagemates. Results: A single intranasal dose of either vaccine elicited systemic and mucosal immunity in K18-hACE2 mice, including serum neutralizing antibodies, Spike-specific memory B cells and plasmablasts, and Spike-specific CD8⁺ lung-resident memory T cells. Although MV-014-212-delta vaccination provided the best protection against the Delta variant virus challenge, both vaccines decreased viral loads in nasal discharge, lung, and brain, and reduced weight loss and mortality. In naturally acquired infection studies, vaccinated hamsters exposed to infected cagemates exhibited minimal weight loss, limited viral replication within the nasal mucosa, and attenuated lung pathology. Conclusions: Intranasal RSV-vectored vaccines can elicit broad protective respiratory immunity, suggesting that this platform could be leveraged for other respiratory pathogens. Full article

This article examines how bordering is experienced in alpine environments undergoing rapid ecological change. Drawing on ethnographic fieldwork conducted between 2024 and 2025 in the transboundary region of the Aosta Valley (Italy), Haute-Savoie (France), and the Canton of Valais (Switzerland), it explores how more-than-human relations become strained, suspended, or reconfigured through infrastructural instability, environmental rupture, and sanitary regulation. Based on a photo-ethnography, the analysis focuses on three empirical cases: infrastructural disruptions in the Val de Bagnes; the collapse of the Birch Glacier in the Lötschental Valley; and the effects of the Lumpy Skin Disease on pastoral practices across transboundary valleys. The article shows that alpine spaces are continuously co-produced by more-than-human assemblages through dynamics, in which bordering emerges not as fixed spatial line but as a conditional relational process unfolding across elevations and over time. By foregrounding interruption, waiting, constrained access, regulated proximity, suspension and exposure, it contributes to posthuman border studies by approaching bordering as a relational dynamic grounded in the material and temporal conditions under which more-than-human relations become practicable or impracticable. Full article

Explosive ordnance (EO), including AXO (abandoned explosive ordnance), IEDs (improvised explosives devices), and UXO (unexploded ordnance), are widely recognised for their blast and fragmentation hazards, but they also represent a persistent and under-addressed source of occupational chemical exposure for explosive ordnance disposal (EOD) personnel. EOD core activities liberate mixed metals and energetic chemicals, resulting in exposures that are multi-route (inhalation of dusts and fumes, dermal loading amplified by sweat and glove occlusion, and ingestion via hand-to-mouth transfer during eating, drinking, or smoking) and multi-temporal (repeated low-dose background plus task-driven spikes), as well as chemically complex. Clinically, this can present as syndromic overlap across acute and chronic domains, with symptoms that are easily misattributed to heat stress, dehydration, infection, or fatigue. Acute effects of concern include neurotoxic presentations (headache, dizziness, confusion, tremor, and seizure), respiratory and mucosal irritation following dust or fume events, gastrointestinal symptoms, and patterns suggestive of acute hepatic or renal stress, particularly when high-intensity tasks occur in hot environments that compound physiologic strain. Chronic outcomes relevant to repeatedly exposed EOD personnel include renal function decline, neurocognitive effects that can degrade operational decision making and safety, persistent haematologic abnormalities, and endocrine disruption signals, with long-latency risks requiring cautious interpretation given sparse longitudinal data and confounding co-exposures. This review synthesises the current evidence base through an EOD lens and translates it into pragmatic clinical and programmatic actions: task-based exposure characterisation; tiered biomonitoring and medical surveillance aligned to operational tempo; incident-triggered assessment pathways after high-residue events; and prevention strategies that work under field constraints, including contamination control zones, hygiene enforcement, glove and respiratory protection optimisation, tool and vehicle decontamination, and measures to prevent secondary transfer and take-home exposure. The central takeaway is practical: EOD programs can reduce morbidity and improve readiness by treating explosive ordnance as a chemical mixture exposure problem, adopting mixture-aware clinical triage, and embedding surveillance and controls that match how EOD work is actually performed. Full article

Agricultural waste streams represent an underutilized source of bioactive compounds with potential to enhance crop resilience under climate stress. We previously showed that volatile compounds (VCs) emitted from waste shiitake fungi beds (WSFBs) promote early rice seedling growth under controlled conditions. Here, we evaluated whether these early-stage effects persist after transplanting and translate into agronomic benefits under field conditions, including the record high temperatures (HTs) of the 2023 growing season in Niigata, Japan. Seedlings of two japonica cultivars, Nipponbare and Koshihikari, were exposed to WSFBs-derived VCs using a non-contact system and subsequently grown in paddy fields across two seasons (2023–2024). WSFBs-VCs-treated (+VCs) plants exhibited enhanced seedling vigor, increased tiller and panicle numbers, higher grain yield per plant, greater 1000-grain weight, and reduced grain chalkiness. Gas exchange measurements at the reproductive stage during the 2023 record HT showed that +VCs plants maintained higher net photosynthetic rate, stomatal conductance, intercellular CO₂ concentration, and transpiration rate, while intrinsic water-use efficiency showed a modest decline consistent with transpirational cooling. Controlled-environment assays revealed enhanced physiological stability supported by upregulation of cytokinin and stress-responsive genes under acute heat stress. Together, these results demonstrate that short-term exposure to WSFBs-derived VCs enhances rice performance under field conditions, including during extreme heat, and highlight their potential as low-cost, waste-derived biostimulants that support sustainable, circular, and climate-resilient rice production. Full article

Outdoor thermal comfort in university courtyards is a key factor influencing students’ environmental experience and the usability of outdoor spaces in hot-arid climates. Courtyard design may also affect the environmental conditions of adjacent classrooms by modifying solar exposure, shading, air movement, and surface heat gain. Accordingly, this study aims to develop optimized design scenarios for improving outdoor thermal comfort in university courtyards through hybrid passive strategies, including vegetation, shading systems, and cool pavements. To achieve this goal, the research adopted a combined field-based and simulation-based methodology. Field measurements and student questionnaires for 292 students were conducted in courtyards and classrooms of three university buildings in Luxor, Egypt. These buildings represent different urban morphologies, courtyard aspect ratios, geometric configurations, and student densities. In parallel, simulation models were developed using ENVI-met V5.6.1 and Rhinoceros V8 with Grasshopper, to test and compare various design scenarios. Field monitoring revealed that wider courtyards with low aspect ratios (0.28–0.38), lacking trees and finished with concrete paving, recorded lower CO₂ concentrations (around 800 ppm), but experienced higher surface and air temperatures. These elevated temperatures negatively affected outdoor thermal comfort and increased heat gain in classrooms overlooking the courtyards. In contrast, courtyards with higher aspect ratios (0.63–0.82) demonstrated better microclimatic moderation and improved comfort conditions. Simulation results indicate that integrating a belt vegetation pattern of Cassia leptophylla, combined with textile shading and cool pavements with an albedo of 0.5, can reduce the Universal Thermal Climate Index (UTCI) by up to 14.7 °C, shifting conditions toward moderate heat stress. The findings provide practical design guidance for upgrading existing university courtyards and designing future educational buildings in hot-arid climates to enhance student comfort and environmental performance. Full article

Nickel-rich NMC-811 is a benchmark cathode material for high-energy density lithium-ion batteries due to its high specific capacity (>200 mAh g⁻¹) and operating voltage (~3.8 V). However, its strong surface reactivity toward atmospheric species, particularly moisture and CO₂, poses significant challenges during storage and processing, leading to the formation of LiOH- and Li₂CO₃-rich surface layers. Although the effects of humid air have been widely investigated, a direct comparison between high relative humidity and pure CO₂ exposure remains limited. Here, we systematically examine the morphological, structural, chemical, and electrochemical evolution of commercial NMC-811 electrodes after 5 h exposure to 80% relative humidity or CO₂-saturated atmosphere. Moisture treatment induces substantial surface reconstruction, lattice shrinkage, and increased cation disorder, accompanied by extensive hydroxide and carbonate formation. In contrast, CO₂ exposure mainly modifies the outermost surface layer without significant bulk structural changes. Electrochemical testing reveals that CO₂-treated electrodes display higher initial polarization but quickly recover near-pristine performance, whereas humidity-treated electrodes exhibit persistent kinetic limitations, accelerated capacity fading, and earlier end-of-life. Overall, degradation severity follows the trend: pristine < CO₂ < RH 80%, highlighting the dominant role of moisture in irreversible structural deterioration. Full article