Search Results (244)

Seasonal fluctuations in the chemical composition of fine particulate matter (PM_2.5) are known to influence its toxicological properties; however, their integrated biological effects remain incompletely understood. In this study, PM_2.5 was continuously collected over two consecutive years at a single urban site in Japan and classified by season. The samples were comprehensively characterized for ionic species, metals, carbonaceous fractions, and polycyclic aromatic hydrocarbons (PAHs), and their pulmonary effects were evaluated in vivo following intratracheal administration in mice. Seasonal PM_2.5 exhibited pronounced compositional differences, with higher levels of secondary inorganic aerosol components in summer and enrichment of PAHs and mineral-associated components in winter. These seasonal differences translated into distinct biological responses. Reactive oxygen species (ROS) production (1.6–2.7-fold increase) and bronchoalveolar lavage (BAL) neutrophil infiltration were strongly associated with PAH-rich PM_2.5, whereas interleukin-1α (IL-1α) showed robust positive correlations with mineral components, including K⁺, Ca²⁺, and Mg²⁺, which were predominantly enriched in winter PM_2.5. In contrast, secondary inorganic aerosol species displayed a limited capacity to induce IL-1α. Compared with summer samples, winter PM_2.5 induced significantly higher levels of ROS production and IL-1α (approximately 1.5–2.6-fold increase). Using TLR2- and TLR4-deficient mice, we further demonstrated that PM_2.5-induced increases in BAL cell counts, ROS, IL-6, and TNF-α were partially attenuated in TLR4 knockout mice, indicating a contributory but not exclusive role for TLR4 signaling in PM_2.5-driven pulmonary inflammation. Collectively, these findings demonstrate that seasonal variations in PM_2.5 composition, not particle mass alone, critically shape oxidative stress and innate immune responses in the lungs. In particular, winter PM_2.5 enriched in mineral-associated components preferentially activates IL-1α-mediated alarmin pathways, underscoring the importance of the particle composition in determining seasonal air pollution toxicity. Full article

Tuberculosis (TB) remains a leading infectious killer, increasingly complicated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) disease; current regimens, although effective, are prolonged, toxic, and often fail to reach intracellular bacilli in heterogeneous lung lesions. This narrative review synthesizes how next-generation antimycobacterial strategies can be translated “from molecule to patient” by coupling potent therapeutics with delivery platforms tailored to the lesion microenvironment. We survey emerging small-molecule classes, including decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) inhibitors, mycobacterial membrane protein large 3 (MmpL3) inhibitors, and respiratory chain blockers, alongside optimized uses of established agents and host-directed therapies (HDTs). These are mapped to inhalable and nanocarrier systems that improve intralesional exposure, macrophage uptake, and targeted release while reducing systemic toxicity. Particular emphasis is placed on pulmonary dry powder inhalers (DPIs) and aerosols for direct lung targeting, stimuli-responsive carriers that trigger release through pH, redox, or enzymatic cues, and long-acting depots or implants that shift daily dosing to monthly or quarterly schedules to enhance adherence, safety, and access. We also outline translational enablers, including model-informed pharmacokinetic/pharmacodynamic (PK/PD) integration, device formulation co-design, manufacturability, regulatory quality frameworks, and patient-centered implementation. Overall, aligning stronger drugs with smart delivery platforms offers a practical pathway to shorter, safer, and more easily completed TB therapy, improving both individual outcomes and public health impact. Full article

The multiple sources and concomitant negative environmental and health impacts of volatile organic compounds (VOCs) in the atmosphere demonstrate their importance in air pollution control. This study employed environment- and health risk-oriented source apportionment methods to quantitatively estimate VOCs’ contribution to air pollution and health risks, using offline VOC measurements from the Harbin urban region from 2021 to 2022. Total volatile organic compounds (TVOCs) averaged 25.6 ± 8.2 ppb, except for alkanes (34.4%), and aromatics (24.2%) were found to be a major contributor, with the highest L_OH (38.0%), ozone formation potential (OFP) (43.0%), and secondary organic aerosol formation potential (SOAFP) (95.0%) and exerting a directly toxic effect (46.0%). Positive matrix factorization (PMF) source apportionment revealed that vehicle exhausts, combustion sources, solvent and coating usage, solvent and fuel evaporation, and petrochemical industry sources were key VOC sources. A health risk assessment showed that there was an integrated carcinogenic risk of 5.8 × 10⁻⁴, with respiratory (1.5 × 10⁻⁴) and hematologic systems (1.5 × 10⁻⁴) representing higher carcinogenic risks. Both benzene and naphthalene exhibited carcinogenic risks of 1.5 × 10⁻⁴, implying an excess of higher cancer risk levels (1.0 × 10⁻⁴). Significant joint environmental and health benefits could be obtained by reducing benzene and naphthalene concentrations by about 50.0%, along with the abatement of vehicle exhausts (82.6%), combustion sources (40.7%), and solvent and coating usage (50.7%). This study can serve as useful guidance for the quantitative mitigation of hazardous VOCs and their key sources. Full article

Electrospinning has advanced from a lab technique to an industrial method, enabling modern filters that are high-performing, sustainable, recyclable, and non-toxic. This study produced recycled PA6 nanofibers using green solvents and incorporated non-toxic CuO nanoparticles via industrial free-surface electrospinning. Polymer solutions with concentrations of 12.5, 15.0 and 17.5 (w/v)% were electrospun directly onto recyclable polypropylene spunbond/meltblown nonwoven substrates to produce nanofibers with average fiber sizes of 80–250 nm. Electrospinning parameter optimization revealed that the 12.5 wt.% PA6 solution and the 2–3 mm·s⁻¹ winding speed had the optimal performance, attaining 98.06% filtering efficiency and a 142 Pa pressure drop. The addition of 5 wt.% CuO nanoparticles increased the membrane density and reduced the pressure drop to 162 Pa, thereby improving the filtration efficiency to 98.23%. Bacterial and viral filtration studies have demonstrated pathogen retention above 99%. Moreover, antibacterial and antiviral testing has demonstrated that membranes trap and inactivate microorganisms, resulting in a 2.0 log (≈approximately 99%) reduction in viral titer. This study shows that recycled PA6 can be converted into high-performance membranes using green, industrial electrospinning, introducing innovations such as non-toxic CuO functionalization and ultra-fine fibers on recyclable substrates, yielding sustainable filters with strong antimicrobial and filtration performance, which are suitable for personal protective equipment and medical filtration. Full article

White-matter development during fetal life represents one of the most vulnerable processes to environmental disruption, as it relies on the precisely timed proliferation, migration, and differentiation of oligodendrocyte lineage cells. Among environmental threats, exposure to toxic compounds contained in tobacco smoke and vaping aerosols represents a major yet preventable risk during pregnancy. Despite growing awareness, tobacco smoking remains widespread, and a substantial proportion of the population—including pregnant women—continues to perceive electronic nicotine delivery systems (ENDS) as less harmful, a misconception that contributes to persistent prenatal exposure. These products expose the fetus to numerous substances that readily cross the placenta and reach the developing brain, including compounds with endocrine-disrupting activity, where they interfere with white-matter development. Epidemiological and neuroimaging studies consistently reveal microstructural alterations in white matter that correlate with long-term cognitive and behavioral impairments in offspring exposed in utero. These alterations may arise from both nicotine-specific pathways and the actions of other toxicants in cigarette smoke and ENDS aerosols that cross the placenta and disrupt white-matter emergence and maturation. Preclinical research provides mechanistic insight: nicotine acts directly on nicotinic acetylcholine receptors (nAChRs) in oligodendrocyte precursor cells, disrupting calcium signaling and differentiation, while additional constituents of smoke and vaping aerosols also affect astrocyte and microglial function and disturb the extracellular milieu required for proper myelination. Full article

Nitrated monoaromatic hydrocarbons (NMAHs) are emerging air pollutants commonly found in biomass burning (BB) and anthropogenic aerosols (AA). Despite their frequent deposition into aquatic systems, their ecotoxicity is still poorly understood. This study evaluates the toxicity of BB and AA aerosol extracts and their main NMAH constituents (nitrocatechols, nitrophenols, and nitrosalicylic acids) using in vitro (cellular uptake, cytotoxicity) and in vivo (algal growth inhibition, zebrafish embryo development) bioassays. Polar aerosol extracts showed higher toxicity than nonpolar ones, with stronger interaction via zebrafish organic anion Oatp1d1 than organic cation Oct1 transporter, indicating selective uptake. NMAHs and their relevant mixtures showed similar toxicity patterns as BB water extract, so NMAHs were identified as contributors to aerosol toxicity. Nitrocatechols stand out for their toxicity, showing the highest chronic toxicity in algae (IC₅₀: 0.6–1.1 mg/L) and acute cytotoxicity in fish cells (IC₅₀: 2.0–4.1 mg/L), possibly because they dominated the NMAHs composition of aerosols (BB: 80.6%; AA: 79.8%). Sublethal NMAH concentrations caused developmental disorders and altered lipid homeostasis in zebrafish embryos, indicating early physiological stress on higher organisms. These findings reveal NMAHs as significant ecotoxic components of BB and AA emissions which may pose an increasing threat to aquatic ecosystems following atmospheric deposition. Full article

The presence of micro- and nano-plastics in the atmosphere has become evident, necessitating risk assessments for humans. Although submerged culture systems are often used to evaluate the safety of fine particles, some plastics float in culture media owing to their low density. Therefore, developing an air–liquid interface (ALI) system capable of assessing plastic exposure is essential. In this study, we developed a chamber for exposing nanoplastic aerosols to ALI cultures and evaluated their toxicological effects. A glass exposure chamber integrated with a donut-shaped culture plate was constructed. The aerosols were introduced through four upper inlets and discharged through five lower outlets. The culture temperature was controlled by circulating water through the inside space of the plate. A nano-polystyrene (PS) suspension was nebulized and introduced into the chamber. Exposure of co-culture of Calu-3 and U937 cells to nano-PS aerosols resulted in a spatial mass concentration-dependent increase in hydrogen peroxide concentration in the culture medium, elevated expression of inflammatory cytokines and chemokines (including IL-6 and IL-8) in Calu-3 cells and decreased trans-epithelial electrical resistance. These findings indicate that nano-PS aerosol exposure induces oxidative stress and inflammatory responses, leading to alveolar barrier dysfunction. Overall, the developed ALI exposure system provides a useful in vitro culture system for evaluating the safety of nanomaterials, including nanoplastics, and highlights the importance of aerosol-based approaches in assessing the toxicity of respirable particles. Full article

This study investigated the pro-inflammatory and pro-oxidative effects of popular electronic cigarette aerosols (ECAs) compared with conventional cigarette smoke (CS) in the cultured human alveolar epithelial cell line (A549). Using cytotoxicity assays and four ECAs, substantial differences in biological impact were observed. CS exposure led to significant declines in cell viability and pronounced morphological changes, consistent with the presence of toxic combustion byproducts. Most ECAs caused negligible cytotoxicity except for the tobacco-flavoured variant, which demonstrated marked toxicity. DNA damage and altered cell cycle profiles were minor. Oxidative stress analysis revealed stable superoxide dismutase activity but notable glutathione depletion, especially with watermelon- and strawberry-flavoured ECAs, and unaltered mitochondrial transmembrane potential, indicating the importance of individual flavour additives in cellular antioxidant defence. Inflammatory markers, such as TNF-α, NF-κB, and IL-6, were differentially elevated across the CS and ECA groups, with IL-6 consistently increased, underscoring its role in regulating epithelial cells. Advanced double fluorescence analysis revealed increased cellular heterogeneity and inflammation, which was distinct for all ECA flavours. Overall, the findings demonstrate considerable heterogeneity in biological effects among ECA flavourings and propose a simple ECA biomonitoring model. The results emphasise the necessity for individualised toxicity assessments, especially regarding subclinical inflammation and potential long-term health outcomes. Full article

Air pollution, particularly from fine and ultrafine particulate matter (PM), has been increasingly associated with cardiovascular diseases. Ultrafine carbon, a component of ultrafine PM widely used in industrial settings, is both an environmental and occupational hazard. But the cardiac toxicity of repeated inhalation exposure to ultrafine carbon black (CB) remains unclear. In this study, we investigated how repeated inhalation of CB affects cardiac mitochondrial function, focusing on metabolic pathways and regulatory mechanisms involved in energy production. Male C57BL/6J mice were exposed to either filtered air or CB aerosols (10 mg/m³) for four consecutive days. Cardiac tissues were collected and analyzed to assess changes in metabolic enzyme activity, protein expression, and mitochondrial function using Western blotting, enzymatic assays, and immunoprecipitation. Despite there being few changes in overall protein expression levels, we observed significant impairments in fatty acid oxidation, increased glucose oxidation, and disrupted electron transport chain (ETC) supercomplex assembly, particularly in Complexes III and IV. These changes were accompanied by increased hyperacetylation of mitochondrial proteins and elevated levels of GCN5L1, a mitochondrial acetyltransferase. We also found increased lipid peroxidation and hyperacetylation of antioxidant enzyme SOD2 at the K-122 site, which reflects reduced enzymatic activity contributing to oxidative stress. Our findings suggest that repeated CB inhalation leads to mitochondrial dysfunction in the heart by dysregulating substrate utilization, impairing ETC activities, and weakening antioxidant defenses primarily through lysine acetylation. These findings reveal a potential role of key post-translational mechanisms in environmental particulate exposure to mitochondrial impairment and provide a potential therapeutic target for CB-induced cardiotoxicity. Full article

With the development of the mining industry, safety issues in underground operations are becoming increasingly relevant. Complex gas conditions in mines, including the presence of explosive and toxic gases, pose a serious threat to the lives of miners and the stability of production processes. This paper describes the development and modeling of an integrated fire monitoring and automatic extinguishing system that combines gas collection, concentration analysis, and rapid response to emergencies. The main components of the system include the following: a gas collection module that uses an array of highly sensitive sensors to continuously measure the concentrations of methane (CH₄), carbon monoxide (CO), and hydrogen sulfide (H₂S) with an accuracy of up to 95%; a gas analysis module that uses data processing algorithms to identify gas concentration threshold exceedances (e.g., CH₄ > 5% vol. or CO > 20 ppm); and an automatic fire extinguishing module that activates nitrogen supply, ventilation, and aerosol/powder fire extinguishers when a threat is detected. Simulation results in MATLAB/Simulink showed that the system reduces the concentration of hazardous gases by 30% within the first 2 s after activation, which significantly increases safety. Additionally, scenarios with various types of fires were analyzed, confirming the effectiveness of the extinguishing modules in mines up to 500 m deep. The integrated system achieves 95% gas detection accuracy, 90 ms response latency, and 40% hazard reduction within 3 s of activation, verified in 500 m deep mine simulations. Quantitative comparison shows a 75% faster response time and 10% higher detection accuracy than conventional systems. The proposed system demonstrates high reliability in difficult conditions, reducing the risk of fires by 75% compared to traditional methods. This work opens up prospects for practical application in the coal industry, especially in regions with a high risk of spontaneous coal combustion, such as India and Germany. Full article

Background: Inhaled delivery of cannabidiol (CBD) through dry powder inhalers is a promising approach for achieving optimal drug concentrations in the lungs. Spray drying is a commonly employed technique to prepare inhalable powders with particle sizes ideally ranging from 1 to 5 µm, for deep lung deposition. However, formulating aerosolizable CBD dry powders remains challenging due to the thermolabile nature of CBD and the cohesive behaviour of micron-sized particles, which affects powder dispersibility, reduces de-agglomeration during inhalation, and causes inefficient lung deposition. These challenges can be overcome by the inclusion of excipients that can stabilize CBD during processing and enhance the dispersion and aerosolization of the powder. Objectives and methods: This study investigates the role of different amino acids (lysine, cysteine, arginine, and phenylalanine) in combination with inulin, a sugar-based excipient, on the in vitro aerosolization performance, stability, and cytotoxicity of inhalable CBD dry powders. Results and conclusion: The prepared CBD dry powders exhibited a size range of 1–5 µm. Amino-acid-free CBD powder showed an irregular and flaky morphology, while in association with amino acids, CBD dry powder showed spherical morphology with a dimpled surface. The ATR-FTIR spectra confirmed no interactions between CBD and amino acids in the dry powder formulations. CBD dry powder formulations containing amino acids demonstrated a better aerosolization profile compared to amino-acid-free CBD powder, with the lysine-containing formulation achieving the highest fine particle fraction (FPF) of 56.6%. Additionally, all the formulations were stable under low and high humidity (<15% RH and 53% RH) conditions for 28 days. Cytotoxicity studies on A549 alveolar basal epithelial cells showed that the amino acids were non-toxic, while the CBD formulations with/without amino acids showed comparable levels of cytotoxicity. Full article

Despite increasing evidence that cigarette smoke is a significant source of indoor fine particulate matter (PM_2.5), quantitative emission factors (EFs) for PM_2.5 and its toxic chemical composition in mainstream (MS) and sidestream (SS) smoke are still not well defined. In this study, we employed a custom-designed chamber to separately collect MS (intermittent puff) and SS (continuous sampling) smoke from eleven cigarette models, representing six brands and two product types, under controlled conditions. PM_2.5 was collected on quartz-fiber filters and analyzed for carbon fractions (using the thermal–optical IMPROVE-A protocol), nine water-soluble inorganic ions (by ion chromatography), and twelve trace elements (via ICP-MS). SS smoke exhibited significantly higher mass fractions of total analyzed species (84.7% vs. 65.9%), carbon components (50.6% vs. 44.2%), water-soluble ions (17.1% vs. 13.7%), and elements (17.0% vs. 7.0%) compared to MS smoke. MS smoke is characterized by a high proportion of pyrolytic organic carbon fractions (OC₁–OC₃) and specific elements such as vanadium (V) and arsenic (As), while SS smoke shows elevated levels of elemental carbon (EC1), water-soluble ions (NH₄⁺, NO₃⁻), and certain elements like zinc (Zn) and cadmium (Cd). The toxicity-weighted distribution indicates that MS smoke primarily induces membrane disruption and pulmonary inflammation through semi-volatile organics and elements, whereas SS smoke enhances oxidative stress and cardiopulmonary impairment via EC-mediated reactions and secondary aerosol formation. The mean OC/EC ratio of 132.4 in SS smoke is an order of magnitude higher than values reported for biomass or fossil-fuel combustion, indicative of extensive incomplete combustion unique to cigarettes and suggesting a high potential for oxidative stress generation. Emission factors (µg/g cigarette) revealed marked differences: MS delivered higher absolute EFs for PM_2.5 (422.1), OC (8.8), EC (5.0), Na⁺ (32.6), and V (29.2), while SS emitted greater proportions of NH₄⁺, NO₃⁻, Cl⁻, and carcinogenic metals (As, Cd, Zn). These findings provide quantitative source profiles suitable for receptor-oriented indoor source-apportionment models and offer toxicological evidence to support the prioritization of comprehensive smoke-free regulations. Full article

Background: Peritoneal metastases (PM) represent a common and challenging manifestation of several gastrointestinal and gynecologic malignancies. Bidirectional treatment—combining Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with systemic chemotherapy—has emerged as a strategy to enhance locoregional control while maintaining systemic coverage. Objective: This systematic review aimed to analyze the study design, characteristics, and timing of the treatments administered—including the type of systemic chemotherapy, intraperitoneal agents used in PIPAC, and interval between administrations—as well as the clinical outcomes, safety profile, and overall methodological quality of the available literature on bidirectional treatment for peritoneal metastases. Methods: A systematic literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to April 2025. Studies were included if they reported clinical outcomes of patients undergoing bidirectional treatment. Data extraction focused on survival, response assessment (PRGS, PCI), adverse events, systemic and intraperitoneal regimens, treatment interval, and study methodology. Results: A total of 22 studies involving 1015 patients (742 treated with bidirectional therapy) were included. Median overall survival ranged from 2.8 to 19.6 months, with the most favorable outcomes observed in gastric and colorectal cancer cohorts. PRGS improvement after multiple PIPAC cycles was reported in >80% of evaluable cases. High-grade adverse events (CTCAE ≥ 3) occurred in up to 17% of patients in most studies, with only one study reporting treatment-related mortality. However, methodological quality was generally moderate, with considerable heterogeneity in treatment protocols, response criteria, systemic regimens, and toxicity attribution. Conclusions: Bidirectional therapy with PIPAC and systemic chemotherapy appears to be a feasible and potentially effective strategy for selected patients with peritoneal metastases. Despite encouraging outcomes, definitive conclusions are limited by the retrospective nature and heterogeneity of available studies. Prospective standardized trials are needed to confirm efficacy, clarify patient selection, and optimize treatment protocols. Full article

Tobacco control policies have aimed to reduce the global prevalence of smoking. Unfortunately, the recent survey data shows that about 24% of Europeans still smoke. Although combustible cigarettes remain the most used tobacco product, the tendency made evident in the prevalence of smoking-alternative nicotine-containing products increases. Studies that can objectively assess the long-term health effects of the latter products are lacking, so assessing toxic substances associated with smoking-alternative products and comparing them to substances from combustible cigarettes could inform future public health efforts. The manufacturers of these alternative products claim that the use of alternatives to combustible cigarettes reduces exposure to toxic compounds, but the reality is unclear. This study compares the concentrations of toxic substances in generated aerosols and performs calculations based on mainstream cigarette smoke and aerosols from smoking-alternative products. It summarizes the amounts of harmful and potentially harmful constituents per single puff. Alternative smoking products are undoubtedly harmful to non-smokers. Still, based on the analysis of the latest independent studies’ empirical data, the concentrations of inhaled HPHCs using heated tobacco products or e-cigarettes are reduced up to 91–98%, respectively; therefore, for those who cannot quit, these could provide a less harmful alternative. However, more well-designed studies of alternative product emissions are needed, including an analysis of the compounds that are not present in conventional tobacco products (e.g., thermal degradation products of propylene glycol, glycerol, or flavorings) to evaluate possible future health effects objectively. Full article

Medellín, a densely populated city in the Colombian Andes, faces significant health and environmental risks due to poor air quality. This is linked to the atmospheric dynamics of the valley in which it is located (Aburrá Valley). The region is characterized by a narrow valley and one of the most polluted areas in South America. This is a comparative study of the chemical composition of PM_2.5 (particles with diameter less than 2.5 µm) in Medellín between two periods (2014–2015 and 2018–2019) in which temporal trends and emission sources were evaluated. PM_2.5 samples were collected from urban, suburban, and rural stations following standardized protocols and compositional analyses of metals (ICP-MS), ions (ion chromatography), and carbonaceous species (organic carbon (OC) and elemental carbon (EC) by thermo-optical methods) were performed. The results show a reduction in average PM_2.5 concentrations for the two periods (from 26.74 µg/m³ to 20.10 µg/m³ in urban areas), although levels are still above WHO guidelines. Urban stations showed higher PM_2.5 levels, with predominance of carbonaceous aerosols (Total Carbon—TC = OC + EC = 35–50% of PM_2.5 mass) and secondary ions (sulfate > nitrate, 13–14% of PM_2.5 mass). Rural areas showed lower PM_2.5 concentrations but elevated OC/EC ratios, suggesting the influence of biomass burning as a major emission source. Metals were found to occupy fractions of less than 10% of the PM_2.5 mass; however, they included important toxic species associated with respiratory and cardiovascular risks. This study highlights progress in reducing PM_2.5 levels in the region, which has been impacted by local policies but emphasizes current and future challenges related mainly to secondary aerosol formation and carbonaceous aerosol emissions. Full article