Search Results (2,314)

Background: The right ventricular free wall longitudinal strain to pulmonary arterial systolic pressure (RVFWLS/PASP) ratio is an emerging echocardiographic index for evaluating right ventricular–pulmonary artery (RV-PA) coupling. This study aimed to evaluate its prognostic significance and incremental value in risk stratification for patients with pulmonary arterial hypertension (PAH). Methods: We conducted a retrospective–prospective cohort study of 149 adult PAH patients (87 idiopathic PAH and 62 connective tissue disease-associated PAH). RVFWLS was measured via speckle tracking echocardiography, and PASP was estimated using Doppler. The primary endpoint was event-free survival, defined as the first occurrence of all-cause mortality, lung transplantation, or rehospitalization for right heart failure. Kaplan–Meier and multivariate Cox regression analyses were performed to identify independent predictors. Results: During a median follow-up of 32 months, 78 primary events occurred. Patients in the lower RVFWLS/PASP group (<0.246%/mmHg) exhibited significantly worse exercise capacity, higher NT-proBNP levels, and poorer hemodynamics compared with the higher group (≥0.246%/mmHg) (all p < 0.001). The event-free survival rate for the composite endpoint was significantly lower in the group with reduced RVFWLS/PASP compared with that observed in the higher RVFWLS/PASP group (log-rank p < 0.05). Multivariate Cox regression analysis demonstrated RVFWLS/PASP ≥ 0.246%/mmHg was independently predictive of reduced risk for the primary endpoint (HR = 0.46, 95%CI 0.23–0.93, p < 0.05). Moreover, RVFWLS/PASP facilitated additional risk stratification among patients classified as low risk based on established models (FPHN, COMPERA 2.0, and REVEAL Lite 2). Conclusions: RVFWLS/PASP is a robust, independent determinant of long-term prognosis in patients with PAH. As a noninvasive measure of RV-PA coupling, it provides significant incremental value for clinical risk assessment and treatment monitoring. Full article

Background/Objectives: Pulmonary arterial hypertension (PAH) is a rare but life-threatening disease that presents particular therapeutic challenges in children. It is characterized by pulmonary vasoconstriction and vascular remodeling, leading to right ventricular strain and eventually right heart failure. Although advances in pharmacotherapy have improved outcomes, treatment options remain limited. This review aims to evaluate the potential role of sotatercept, a novel fusion protein recently approved for adult PAH, and to assess the translatability of adult data to the pediatric population. Methods: A narrative synthesis of preclinical studies and randomized controlled trials was conducted to summarize the current evidence on sotatercept. In addition, pathophysiological, developmental, and therapeutic differences between adult and pediatric PAH were critically examined to assess relevance and applicability to younger patients. Results: Clinical trials in adults (PULSAR, STELLAR, ZENITH, HYPERION) confirm sotatercept’s efficacy on background therapy, with significant reductions in pulmonary vascular resistance, improvements in 6 min walk distance, enhanced right ventricular function, and risk reductions in clinical worsening events. However, extrapolation to pediatric PAH faces challenges including etiological differences (e.g., PAH-CHD predominance, PPHN in infants), age-inappropriate endpoints (e.g., 6MWD infeasible in young children), variable growth-related pharmacokinetics, and compensatory RV physiology delaying overt failure. Safety concerns are manageable in adults but raise pediatric-specific alarms: activin inhibition’s theoretical tumorigenic potential (dual tumor suppressor/promoter role), pubertal/fertility disruption (FSH suppression, gonadal maturation delay), and skeletal growth interference—unproven clinically yet demanding long-term monitoring. The ongoing MOONBEAM trial will provide initial pharmacokinetic/safety data in children. Conclusions: Sotatercept represents a promising, first-in-class therapeutic option for PAH with the potential to transform disease management. Nevertheless, dedicated pediatric studies are crucial to confirm safety, efficacy, and appropriate dosing and to define its role in the long-term treatment of children with PAH. Full article

This work investigates the physicochemical characteristics of waste tire pyrolysis char (WTP-char) produced at 500 °C in an industrial-scale auger reactor. The study uniquely combines material profiling with environmental safety assessment, specifically targeting organic contaminants and polymer stabilizers, evaluating WTP-char’s potential for circular economy applications. The samples underwent comprehensive analysis, including GC-MS, TGA, SEM-EDS, TXRF, and BET surface area measurements. The results revealed a high volatile matter content (13 wt.%), attributed to the thermal inertia typical of industrial-scale units. The organic fraction was dominated by n-alkanes (48.3%) and a significant concentration (6.97%) of the stabilizer Tris(2,4-di-tert-butylphenyl) phosphate (bDtBPP), posing potential environmental risks due to its cytotoxicity. Polycyclic aromatic hydrocarbon (PAH) analysis showed a prevalence of high-molecular-weight (HMW) compounds (79.7%), indicating high chemical stability. Although the specific surface area was low (28.9 m²/g), suggesting the need for activation, the material exhibits potential as a low-cost semi-reinforcing filler or solid fuel. By moving beyond laboratory-scale experiments to real industrial production, this study establishes a practical framework for evaluating both the performance and environmental safety of waste tire pyrolysis char. Full article

Objectives: Downregulation of the endogenous gasotransmitter hydrogen sulfide (H₂S) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). While prophylactic H₂S supplementation prevents PAH initiation in different rat models, its ability to reverse fully established PAH and pulmonary vascular structural remodeling is unknown. In this study, we aimed to test whether H₂S donor therapy can reverse the existing PAH in a chronic-hypoxia rat model. Methods: After 3 weeks of hypoxia exposure, rats with established hypoxia-induced pulmonary hypertension (HPH) were randomized to receive either continued hypoxia alone or hypoxia plus the H₂S donor NaHS (56 μmol/kg·d, ip) for an additional 6 weeks. Pulmonary artery pressure, pulmonary artery muscularization, and right ventricular hypertrophy were assessed. Furthermore, the cell proliferation (Ki-67 and PCNA), ERK1/2 phosphorylation, and persulfidation of the endothelin type A receptor (ETAR) were examined and detected in rat lung tissues and pulmonary artery smooth muscle cells (PASMCs). Results: H₂S therapy effectively reversed established HPH and pulmonary artery structural remodeling, reducing RVSP, mPAP, and the proportion of fully muscularized small pulmonary arteries by 13.8%, 12.0%, and 62.7%, respectively. Moreover, the PAT/PET ratio was normalized to normoxic levels. The right ventricular hypertrophy index decreased by 29.2%. Mechanistically, H₂S therapy suppressed PASMC proliferation, reduced ERK1/2 phosphorylation, and enhanced ETAR persulfidation. Furthermore, dithiothreitol-mediated reduction of ETAR persulfidation abrogated these antiproliferative effects of H₂S therapy, establishing persulfidation as an obligatory mechanism. Conclusions: H₂S donor therapy effectively reverses established HPH and pulmonary vascular structural remodeling by inhibiting PASMC proliferation, which is linked to enhanced ETAR persulfidation. These data provide preclinical proof-of-concept for H₂S-based interventions in patients with manifest PAH. Full article

The Black Sea is highly vulnerable to environmental degradation, making the evaluation of contaminant transfer within its food webs essential for ecosystem protection, sustainable resource management, and human health risk assessment. Marine organisms accumulate contaminants through three main processes: bioconcentration (direct uptake from the abiotic environment), biomagnification (trophic transfer through consumption of contaminated prey), and bioaccumulation, which integrates contaminants from all exposure pathways. Despite numerous studies reporting contaminant concentrations in Black Sea waters, sediments, and biota, integrated analyses of trophic transfer within both pelagic and benthic food webs in the Romanian coastal sector remain limited. This study assessed the bioamplification of heavy metals—HMs, persistent organic pollutants—POPs (OCPs, PCBs) and polycyclic aromatic hydrocarbons—PAHs along the main pelagic and benthic food webs in the Romanian coastal sector, based on concentrations measured in representative invertebrate and fish species. The results revealed a compartment-driven contamination pattern, with the benthic food web functioning as an important reservoir and transfer pathway. Heavy metals showed variable and context-dependent trophic transfer, with selective amplification for Cu and Ni in some benthic links, trophic dilution or neutral transfer for Cd and Pb, and more consistent retention for Cr. In contrast, several PCB congeners showed clear biomagnification, particularly in benthic predator–prey relationships. PAHs displayed compound-dependent trophic transfer, with more pronounced amplification in benthic pathways. Overall, biomagnification was stronger for organic pollutants, particularly PCBs, than for heavy metals. The study contributes to two United Nations Sustainable Development Goals (SDGs): SDG 14 (Life Below Water) and SDG 12 (Responsible Consumption and Production). Full article

This study investigated the characteristics and interrelationships of polycyclic aromatic hydrocarbons (PAHs), phthalate esters (PAEs), and microbial communities in coastal river sediments and benthic mollusks collected from an e-waste recycling area in Taizhou, Zhejiang Province. In sediments, 16 PAHs and six PAEs were detected, with concentrations ranging from 2.66 to 379.99 μg/kg and 76.5 to 3426.57 μg/kg, respectively. Four-ring PAHs (particularly fluoranthene and pyrene) and Bis(2-ethylhexyl) phthalate (DEHP) were dominant, with DEHP posing a potential risk, especially at site 10, warranting further attention. In contrast, only eight PAHs and four PAEs were detected in mollusks, with concentrations of 60.14–523.10 μg/kg and 144.55–3005.71 μg/kg, respectively. Two-ring PAHs (particularly naphthalene) and Dibutyl phthalate (DBP) were dominant, likely derived directly from the overlying water. The PAHs in sediments primarily originated from fossil fuel combustion, biomass burning, and coal combustion, while PAEs were likely derived from the release of plastic waste from solid waste recycling. Lower concentrations and fewer PAH and PAE species were observed in the sediments near the ocean and at greater distances from the e-waste recycling sites. Significant differences were observed in microbial communities between sediment and mollusk samples. Dominant phyla shared by both sample types include proteobacteria, bacteroidetes, firmicutes, and acidobacteria. The concentration of low-ring PAHs was correlated with the microbial communities, particularly in mollusk samples. Relationships were also identified between microbial communities and DEHP concentrations in sediments or DBP concentrations in mollusks. Full article

Chronic exposure to benzo[a]pyrene (BaP), a Group 1 IARC carcinogen, is a major driver of lung carcinogenesis; however, how sustained subcytotoxic exposure reprograms bronchial epithelium toward preneoplastic states remains poorly defined. Here, we subjected BEAS-2B human bronchial epithelial cells to 12 weeks of continuous BaP at environmentally relevant concentrations (0.1 and 1.0 µM) and interrogated the resulting phenotypes using an integrated multi-scale framework encompassing functional toxicology, RT-qPCR, RNA-seq, phospho-kinase/NF-κB arrays, and organotypic air–liquid interface (ALI) cultures. Cells maintained metabolic competence throughout, evidenced by sustained CYP1A1 and CYP1B1 induction at both acute (4 h) and chronic (12-week) timepoints, while accumulating genotoxic stress as demonstrated by dose-dependent nuclear γ-H2AX foci formation and ATM phosphorylation (Ser1981). RNA-seq revealed a dose-dependent transcriptional shift: 0.1 µM BaP yielded 119 differentially expressed genes (DEGs; |log2FC| ≥ 1, FDR < 0.05), whereas 1.0 µM generated 255 DEGs. Downregulated transcripts were enriched for extracellular matrix and cell-adhesion programs (COL14A1, ADAMTS2, CSMD3, CADM3), while upregulated genes encompassed inflammatory, calcium-signaling, and vesicle-trafficking modules (NFATC4, CSF2RA, SYT1, PCLO). Phospho-kinase/NF-κB arrays confirmed a p53/NF-κB signaling nexus, with concurrent activation of MAPK/ERK (Thr202/Tyr204) and PI3K/Akt (Ser473) pathways. Despite persistent genotoxic stress, cells did not acquire anchorage-independent growth and remained non-tumorigenic in vivo. Critically, ALI organotypic cultures derived from BaP-exposed cells exhibited histological dysplasia, nuclear pleomorphism, and disrupted apical-basal polarity. These findings mechanistically link chronic BaP exposure to an initiation-like preneoplastic state and establish a validated 2D/3D multi-omics platform for PAH-driven lung carcinogenesis research. Full article

This study investigates the key performance-related fuel properties of emulsifier–diesel solutions and ethanol-in-diesel microemulsions. This work begins with the in situ polymerization of long alkyl chain-substituted glycidyl methacrylate (R-GMA) in diesel and the optional presence of a second methacrylate monomer. The resulting diesel-soluble oligomer functions as a nonionic emulsifier. Controlled amounts of ethanol are subsequently incorporated into the emulsifier–diesel solution to form a stable microemulsion, referred to as E-Diesel. This study examines how the structure of the emulsifier influences key fuel properties, including (i) ethanol–diesel miscibility, (ii) gross calorific value, (iii) Ramsbottom carbon residue (% of fuel), (iv) entrapped polycyclic aromatic hydrocarbons (PAHs), and (v) fuel lubricity. Both the hydrophilic–hydrophobic balance and the structure of the emulsifier side chains are found to significantly affect these properties. Compared with neat diesel, oligomeric emulsifiers enable the substantial dispersion of ethanol in diesel (up to 18 wt.%). The resulting fuel exhibits a gross calorific value exceeding the theoretical sum of diesel and ethanol at the same composition (a synergistic effect) and achieves an enhancement in lubricity up to 49.5% relative to neat diesel at a 5% emulsifier loading. Although the presence of emulsifiers leads to an increase in the carbon residue by up to 54.7% compared to neat diesel during controlled pyrolysis, it simultaneously reduces the PAH content in the exhaust. Overall, this study establishes fundamental correlations among microemulsion stability, combustion synergy, carbon residue formulation, and fuel lubricity, which are governed by the structure of the emulsifier. Full article

Right ventricular pressure overloading [RVPO] with secondary maladaptive RV remodeling and progressive myocardial dysfunction in patients with pulmonary hypertension associated with left-sided heart diseases [PH-LHDs] and in those with pulmonary arterial hypertension [PAH] still remains one of the most complex challenges in cardio-pulmonary medicine. Despite the advances in the optimization of diagnostic tools and the expansion of treatment options, there is still a great need for further research to gain a better understanding of the major pathophysiological mechanisms involved in both the RV responses to PO and to find new possibilities to stop the progression of the alterations inside the pulmonary arterial circulation [PAC]. This article summarizes current knowledge about the particularities of the RV structural and functional responses to abnormal PO and also provides an overview of the benefits and limitations of the currently available tools for clinical evaluations of the RV adaptability to high afterload. A major focus of this review relates to the possibilities for obtaining evidence about the existence of a still remaining adaptability to a normal afterload in an over-burdened RV, in case of abolition of the pathological PO and, in this regard, to also evaluate the clinical usefulness of the RV adaptability estimation for certain critical therapeutic decisions. Among the most important conclusions of this updated overview are: 1. Whereas single parameters are insufficiently reliable for the evaluation of RV dysfunction and for predictions of its prognostic relevance across the whole spectrum of RVPO, properly selected and integrated multiparametric approaches had meanwhile unequivocally proved that they can usually become sufficiently reliable. 2. Multiparametric approaches can substantially improve the prediction of a preserved RV responsiveness to the abolition of its steady PO by reversal of RV maladaptive remodeling and by the normalization of RV pump function. Such a prediction, which can be decisive for therapeutic decision-making especially in candidates for ventricular assist device [LVAD] implantation or thoracic organ transplantation, can have a crucial impact on patient survival. 3. The complex and temporally highly variable interactions between certain structural and functional changes in both the PAC and in the hemodynamic overloaded right-sided heart, as well as between the two ventricles, can often hamper the interpretation of certain changes in the measured parameters and even relevantly alter their reliability. Additionally, the progressive aggravation of a secondary tricuspid regurgitation [TR] has a particularly high negative (often also misleading) impact on the diagnostic and prognostic relevance of RVPO evaluations. Full article

Bioturbating animals move around large amounts of sediment, changing its physicochemical properties and biogeochemical processes. The present study assessed the role of the ghost shrimp Lepidophthalmus louisianensis, a major coastal bioturbator in the Northern Gulf of Mexico, in the fate of crude oil after the 2010 Deepwater Horizon blowout. Experiments were conducted in greenhouse mesocosms, with or without ghost shrimp and with or without added oil, reflecting mild surface or subsurface oiling in a beach environment. To evaluate the hydrocarbon-degradation potential of the sediment microbial community, a respirometric radiotracer assay was conducted with ¹⁴C naphthalene as a model polycyclic aromatic hydrocarbon (PAH) compound. Oil augmentation led to a substantial increase in the PAH degradation potential of mesocosm sediments, which was further enhanced by the presence of the bioturbator. However, bioturbation alone, without previous oil exposure, did not enhance naphthalene degradation. 16S rRNA gene analyses showed that there were no significant changes in the microbial community composition associated with either bioturbation, oil augmentation, or both. This study demonstrated bioturbation- and oil-exposure-related enhancement in hydrocarbon degradation in mildly oiled sediment, and indicated that this may be due to an increased expression of PAH degrading activities in the preexisting community of hydrocarbon-degrading bacteria rather than resulting from a shift in the microbial community composition. Full article

The occurrence and spatial distribution of polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), fragrances, UV filters and photoinitiators were investigated in surface sediments of Nerbioi-Ibaizabal estuary between 2005 and 2013, in 2020. Samples were extracted by focused ultrasound solid–liquid extraction technique and analyzed by gas chromatography coupled with mass spectrometry. Total PAHs, PCBs, OCPs, musks, UV filters and photoinitiators concentrations ranged between not detected (n.d.) and 43000 ng g⁻¹, n.d. and 2500 ng g⁻¹, n.d. and 820 ng g⁻¹, n.d. and 880 ng g⁻¹, n.d. and 91 ng g⁻¹ and from nd to 120 ng g⁻¹, respectively. Hexachlorocyclohexanes (HCHs) were ubiquitous in the estuary, suggesting that these compounds, although banned, leach from landfills. The PCB concentrations showed a decreasing trend. Ecological risk assessments based on sediment quality guidelines (SQGs) and risk quotient (RQ) suggested semi-volatile organic compounds could represent a potential ecological risk in the Nerbioi-Ibaizabal estuary. Full article

Polyelectrolyte microcapsules (PMCs) fabricated by layer-by-layer assembly require predictable shell stability for applications in drug delivery, biosensing, and environmental remediation. While core template type is known to influence stability, the role of polyelectrolyte layer number in governing poly(allylamine hydrochloride) (PAH) desorption remains poorly understood. This study quantitatively assessed PAH desorption from fluorescein isothiocyanate (FITC)-labeled shells of PMCs templated on CaCO₃ or MnCO₃ cores with 7, 9, or 13 layers under varying ionic conditions (distilled water, NaCl 0.2–3.0 M, Na₂SO₄ 0.005–1 M) over 168 h. Short-term incubations revealed no significant layer-dependent desorption differences for either core type. However, prolonged exposure uncovered a non-monotonic relationship for CaCO₃-templated PMCs: 7-layer capsules exhibited high initial but limited subsequent release (<50% increase), 9-layer capsules showed minimal initial dissociation followed by maximal kinetic amplification (up to 2000% increase), and 13-layer capsules displayed intermediate behavior. In contrast, MnCO₃-templated PMCs demonstrated uniformly low initial dissociation with gradual time- and concentration-dependent release irrespective of layer number. These findings establish core template nature as the dominant factor controlling dissociation kinetics, while layer number enables fine-tuning of release profiles—particularly for CaCO₃ systems—providing design principles for controlled-release applications requiring delayed or sustained payload delivery. Full article

Human skin and hair act as multifunctional barriers but are highly sensitive to environmental pollutants originating from air, water, and cosmetic products. Epidemiological studies report that exposure to particulate matter (PM_2.5–PM₁₀), nitrogen oxides (NO_x), and volatile organic compounds increases the risk of skin and hair disorders. For instance, women in high-traffic areas (N = 211) show significantly more pigment spots and nasolabial wrinkles compared to those in rural areas (N = 189), indicating accelerated skin ageing. Children aged 9–11 exposed to PM₁₀, benzene, and NO_x exhibit increased incidence of atopic dermatitis. Systemic exposure to dioxins causes chloracne, while co-exposure to polycyclic aromatic hydrocarbons (PAHs) and UVA radiation elevates skin cancer risk. Psoriasis flares are associated with mean pollutant concentrations over the 60 days preceding flare events in 957 patients, and hyperpigmentation prevalence increases in populations exposed to traffic-related PM and ROS-inducing pollutants. Hair loss is linked to oxidative stress from PM and PAHs absorbed on hair fibers, with in vitro studies showing keratinocyte apoptosis in scalp hair follicles. This review evaluates natural adsorbents such as zeolites, clays, activated carbon, and polyphenol-rich plant extracts for anti-pollution cosmetic formulations. Adsorption capacities range from 60 to 150 mg·g⁻¹ depending on the pollutant, with removal efficiencies of 30–55% in model topical systems. Mechanisms include ion exchange, surface adsorption, hydrophobic interactions, and radical scavenging. Incorporating 2–5% w/w of these adsorbents in cosmetic formulations significantly reduces pollutant deposition on skin and hair. These findings support the development of evidence-based, sustainable anti-pollution cosmetic strategies that quantitatively mitigate environmental stressor effects. Full article

Pulmonary arterial hypertension (PAH) has traditionally been viewed as a vasculocentric disorder, with current therapies failing to reverse vascular remodeling or address pervasive systemic metabolic abnormalities. This review synthesizes emerging evidence to propose a paradigm shift, conceptualizing PAH as a systemic metabolic–immunological network disease. It examines how metabolic dysfunction in peripheral organs (adipose tissue, liver, skeletal muscle) and immunometabolic reprogramming of immune cells (e.g., macrophages, lymphocytes) synergistically drive pathology. These components engage in dynamic crosstalk via circulating mediators (metabolites, adipokines, cytokines), creating a self-amplifying loop that fuel pulmonary vascular inflammation and remodeling. Key mechanisms explored include adipose tissue endocrine dysfunction (contributing to the obesity paradox), hepatic insulin resistance and bile acid signaling, skeletal muscle energy crisis and wasting, and the pivotal roles of macrophage glycolytic polarization and T-cell subset imbalance. Insulin resistance/hyperglycemia emerges as a central hub linking metabolic and immune dysregulation. The review concludes that future therapeutic strategies must move beyond vasodilation to target this systemic network, discussing the potential of repurposed metabolic agents, direct immunometabolic modulators, and integrated lifestyle interventions to disrupt disease progression. Full article