Search Results (62,203)

Background/Objectives: Air pollution is associated with many adverse health consequences, including deteriorated kidney function. The aim of the research was to determine the association of medium-term exposure to air pollutants and hospitalizations due to acute kidney injury (AKI). Methods: The retrospective population-based study was conducted on the EP-PARTICLES cohort between 2011 and 2020 (80,000,000 person-years). We estimated municipality-specific associations between air pollution and AKI admissions using generalized additive models with Poisson regression. Results are reported as risk ratio in AKI admissions (RR) with corresponding 95% confidence intervals (95% CI). Results: During the 10-year study period, 47,467 AKI cases were reported (median age 77 years, IQR 68–84; 51.2% women). Mean concentrations of pollutants were 21.4 µg/m³ (SD 5.2) for particulate matter with a diameter of 2.5 μm or less (PM_2.5), 7.5 µg/m³ (1.8) for nitrogen dioxide (NO₂), and 1.8 ng/m³ (0.8) for benzo[a]pyrene (BaP). In mid-term exposure analyses (lag 0–30), each 10 µg/m³ increase in PM_2.5, PM₁₀, NO₂ and CO, and each 1 µg/m³ increase in BaP, was associated with higher AKI risk, with the strongest effect observed for NO₂ (RR 1.066, 95% CI 1.033–1.099). No association was found for SO₂. Subgroup analyses showed consistent directions of association across sex and age groups, with NO₂ remaining the most detrimental pollutant. Although statistical significance varied between pollutants, no significant effect modification by sex or age was observed (p > 0.05). Conclusions: Mid-term exposure to ambient air pollution is associated with an increased risk of AKI-related hospitalizations, with NO₂ showing the strongest effects. These findings identify mid-term exposure as a relevant temporal window and support the role of air pollution as a modifiable risk factor for AKI. Full article

Lactate is increasingly recognized as a signaling molecule capable of modulating gene expression and vascular function. This descriptive pilot study investigated the effects of different lactate concentrations (0 mM, 10 mM, 20 mM, and 30 mM) and exposure times (1 h, 3 h, and 6 h) on the transcriptomic responses of human umbilical vein endothelial cells (HUVECs). Using next-generation RNA sequencing, an unbiased genome-wide analysis was performed, followed by focused examination of genes relevant to endothelial biology, calcium signaling, and glycocalyx integrity. Results showed that there was no statistically significant effect of lactate concentration on the expression of the examined genes. In contrast, prolonged incubation time was associated with differential expression of KLF2, KLF4, FOXO1, CD34, and VCAM1. These findings suggest that exposure time, rather than lactate concentration, may be associated with endothelial gene expression patterns under static conditions. This exploratory pilot study provides preliminary transcriptomic observations and highlights the need for further mechanistic investigations including functional and protein-level analyses. Full article

Background: Menopause represents a critical physiological transition associated with hormonal changes that influence both metabolic health and quality of life (QoL). Metabolic dysfunction-associated steatotic liver disease (MASLD), a common metabolic condition, is closely linked to menopause; however, its independent contribution to QoL impairment remains unclear. This study aimed to investigate the interplay between menopausal status, metabolic dysfunction, MASLD, and QoL in midlife women. Methods: A cross-sectional observational study was conducted including 80 women aged 45–55 years, comprising both premenopausal and menopausal participants. Clinical, anthropometric, biochemical, and imaging data were collected. MASLD was diagnosed using magnetic resonance imaging in the presence of metabolic dysfunction. Metabolic assessment included glucose, insulin, liver enzymes, C-reactive protein, and indices of insulin resistance (HOMA-IR) and sensitivity (QUICKI). QoL was evaluated using the Utian Quality of Life (UQOL) scale. Associations were examined using univariate and multivariable linear regression models. Results: MASLD prevalence was significantly higher in menopausal women compared with non-menopausal women (61.9% vs. 15.8%, p < 0.001). Metabolic parameters, particularly insulin resistance and body mass index, were strongly associated with MASLD. The mean total UQOL score indicated moderate QoL. In multivariable analysis, menopausal status was the only independent predictor of reduced total QoL (b = −4.93, p = 0.01) and occupational health domain (b = −4.60, p = 0.001). MASLD and metabolic parameters were not independently associated with overall QoL. Correlation analyses revealed modest associations between metabolic markers and specific QoL domains, particularly occupational and physical health. Conclusions: Menopause is the primary determinant of reduced QoL in midlife women, particularly affecting functional domains, while MASLD does not independently impact QoL despite its strong association with metabolic dysfunction. These findings suggest that menopausal status may play a more prominent role in quality-of-life outcomes than MASLD in women undergoing the menopausal transition. However, the cross-sectional design does not allow conclusions regarding causal or mechanistic relationships. Full article

Background: Physical inactivity is a major contributor to cardiometabolic disease and mortality. Although mitochondrial dysfunction characterizes overt pathology, whether sedentarism constitutes a distinct and measurable bioenergetic disease state, rather than simply reduced fitness, has not been established. Methods: Nine sedentary (SED) and ten physically active (AC) healthy males (42 ± 14 yr) were studied. Skeletal muscle bioenergetics were assessed using high-resolution respirometry, fluxomics, metabolomics, and protein expression analyses. Whole-body physiology was evaluated using cardiopulmonary exercise and lactate testing (CPELT). Results: At rest, SED exhibited marked reductions in mitochondrial capacity, including Complex I (−36%), Complex II (−28%), electron transport system capacity (−34%), and ATP-synthase-coupled respiration (−30%, all p < 0.01). The most pronounced alteration was a 49% reduction in mitochondrial pyruvate carrier (MPC1) expression, which closely correlated with reduced pyruvate oxidation (−37%, p = 0.006) and lower TCA intermediates. SED also showed reduced MCT1 abundance, impaired fatty-acid oxidation capacity (−32% to −35%), decreased CPT1 activity (−51%), altered cardiolipin composition, and elevated ROS/O₂ flux ratios. During exercise, SED demonstrated lower VO₂max (−38%), reduced fat oxidation (−35%), and higher blood lactate accumulation (>60%, p < 0.001). Mitochondrial function was strongly associated with exercise performance (r = 0.57–0.78, p < 0.01). Conclusions: Healthy sedentary adults displayed a coordinated reduction in tissue-level mitochondrial oxidative capacity, substrate-handling markers, cardiolipin abundance, and metabolic flexibility. These findings should be interpreted as an integrated per-mg skeletal-muscle bioenergetic phenotype in which lower mitochondrial density may account for much of the observed reduction. Within this phenotype, the 49% reduction in MPC1 alongside preserved GLUT4, LDHA, and LDHB abundance represents an outstanding differential observation that future studies with direct mitochondrial-content normalization should test. CPELT-derived fat oxidation and blood lactate responses reflected this tissue-level bioenergetic phenotype, providing candidate noninvasive physiological markers for future longitudinal and interventional studies. Full article

Background and Clinical Significance: Hyaluronic acid fillers are currently the most widely used materials in aesthetic medicine and represent one of the most frequently performed minimally invasive procedures worldwide. Vascular occlusion is the most severe complication associated with this type if filler injections due to the risk of tissue necrosis and permanent sequelae. Early recognition and precise identification of the affected vascular territory are essential to prevent irreversible damage. Case Presentation: his report describes a case of infraorbital artery occlusion with retrograde extension to the anterior superior alveolar artery and associated gingival ischemia, highlighting the role of high-frequency ultrasound in diagnosis and management. A 60-year-old woman developed vascular occlusion following supraperiosteal HA injection in the medial cheek. Clinical findings included livedo reticularis in the infraorbital and nasal regions, along with ipsilateral gingival anesthesia and mucosal ischemia. High-frequency ultrasound was used to assess the extent and mechanism of vascular involvement. A targeted treatment approach was implemented using low-dose hyaluronidase (100 IU/mL), with 200 IU administered in the infraorbital region and an additional 100 IU delivered under ultrasound guidance to the affected alveolar branch. Ultrasound examination revealed extrinsic compression of the infraorbital artery and secondary occlusion of the anterior superior alveolar artery consistent with retrograde embolization. Following image-guided administration of hyaluronidase, complete reperfusion was achieved, with resolution of both cutaneous and gingival ischemia and no functional or aesthetic sequelae. Conclusions: High-frequency ultrasound provides critical diagnostic information in vascular complications after HA filler injection, allowing for accurate identification of the mechanism and extent of vascular involvement. Ultrasound-guided low-dose hyaluronidase may represent an effective and safe strategy to restore perfusion while minimizing unnecessary enzyme exposure and associated adverse effects. Full article

Background: Bacterial adaptation to environmental and chemical stress involves coordinated, system-level responses collectively described as perturbome. Understanding conserved elements within core perturbomes may reveal strategic vulnerabilities for antimicrobial development. Methods: In this study, we implemented an integrative framework combining functional and comparative genomics, drug–target interactions and molecular docking to prioritize conserved stress-response targets in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Results: A total of 147 genes from previously defined core perturbomes were analyzed through interactome reconstruction and functional enrichment. Interactome and functional analyses revealed significant connectivity and functional clustering, primarily associated with molecule biosynthesis, translation, transcriptional regulation, and energy metabolism. Orthology-based comparative genomics identified six conserved orthogroups shared across at least two species, representing key stress-adaptive nodes including fatty acid synthesis initiation, metabolic stress buffering, transcription termination (Rho), ATP synthesis, peptidoglycan remodeling, and UDP-glucose-mediated envelope biosynthesis. Drug–target interaction analyses suggested that these conserved proteins are modulated by enzymatic inhibitors, metabolite analogs, or active-site competitors. Structural and docking analyses focused on a selected protein, FabF (β-ketoacyl-ACP synthase II) and confirmed catalytically coherent binding of cerulenin within the active site, with high concordance between experimentally resolved and AlphaFold-predicted structures, supporting the reliability of structure-based prioritization. Conclusions: Overall, the results demonstrate that bacterial stress responses converge on evolutionarily conserved metabolic and regulatory elements essential for homeostasis and tolerance to perturbations, being the first work integrating core perturbome data from different microorganisms. The proposed perturbome-informed framework provides a rational strategy to identify robust, broad-spectrum antimicrobial targets and highlights opportunities for drug repurposing and future experimental validation. Full article

Urban green infrastructure is increasingly exposed to fine-scale thermal heterogeneity generated by anthropogenic point-source heat emissions, yet the leaf-level responses of adjacent vegetation to such localized stress remain poorly understood. Here, we examined whether air-conditioner (AC) exhaust, a widespread point-source heat emitter, is associated with functional trait shifts in Fraxinus chinensis street trees, and whether easily measurable leaf traits can serve as candidate indicators for ecological monitoring. Using a matched treatment–control field comparison, we compared trees located 2 m from operating AC units with unaffected controls and quantified nine leaf functional traits together with concurrent microclimate variables. AC exhaust created a distinct compound heat–drought–wind micro-environment at the 2 m patch scale, with higher air temperature (+6.3 °C), lower relative humidity (−12.3 percentage points), and higher wind speed (5.2-fold). Exposed trees showed a coordinated shift toward more resource-conservative leaf traits: leaf dry matter content (+14.8%), tissue density (+13.6%), leaf thickness (+6.3%), and stomatal density (+11.7%) increased significantly, whereas specific leaf area (−10.6%), leaf area (−12.5%), chlorophyll content index (−4.6%), and stomatal area (−10.4%) decreased significantly. The observed “small-and-numerous” stomatal configuration suggests altered stomatal regulation, although its implications for transpiration-driven cooling require direct physiological validation. Exploratory structural equation modeling suggested associations among AC-exhaust exposure, leaf economic strategy, and stomatal traits; stomatal regulation showed the highest proportion of model-explained variance (R² = 0.598), but this value should not be interpreted as direct evidence of impairment severity or restoration potential. Leaf dry matter content, specific leaf area, and stomatal density emerged as sensitive and practical candidate indicators of AC-exhaust-associated leaf functional shifts. These findings support precautionary management near AC exhaust outlets, while specific planting-distance thresholds and zoning frameworks require future validation through distance-gradient or manipulative experiments. Full article

Direct sea discharge outlets served as critical conduits for urban sewage and industrial wastewater disposal, playing dual roles as pollutant dilution channels and hotspots for pathogens and antibiotic resistance genes. Traditional monitoring approaches relying on physicochemical parameters and fecal indicator bacteria failed to capture the latent and cumulative risks posed by complex microbial communities. In this review, a holistic microbiome perspective was adopted to systematically synthesize current knowledge on the bacterial community dynamics, assembly mechanisms, resistome–virulome coupling patterns, mobilome-associated risk characteristics, and emerging biomonitoring strategies in direct sea discharge outlets. By integrating high-throughput multi-omics technologies with ecological network analysis and machine learning, we delineated a paradigm shift from cataloging microbial presence to deciphering functional interactions, risk propagation dynamics, and proactive surveillance strategies. Furthermore, under the “One Health” framework, we discussed emerging research frontiers and future challenges in managing pollution at discharge outlets, aiming to provide a scientific basis for environmental risk management in coastal zones. Full article

Background: Dynamic risk stratification is fundamental to the modern management of pulmonary arterial hypertension (PAH). However, data on the impact of sequential add-on therapy in patients with Group 1.4 PAH—particularly in Latin American populations—remains limited. This study evaluated changes in risk classification using COMPERA 2.0 and REVEAL Lite 2 scores in patients treated with endothelin receptor antagonist (ERA) and phosphodiesterase type 5 inhibitor (PDE5i) combination therapy (macitentan + sildenafil) at a referral center in Mexico. Methods: In this single-center, retrospective cohort study, 25 patients with a confirmed diagnosis of PAH between 1st January 2022 and 31st December 2024 were evaluated at baseline and after 24 weeks of treatment. Clinical, functional, and biochemical parameters were recorded. Within-patient changes were analyzed using the Wilcoxon signed-rank test, and agreement between risk assessment tools was assessed using Spearman’s correlation coefficient. Results: At 24 weeks, patients demonstrated significant improvement in World Health Organization functional class (p = 0.002) and a significant reduction in brain natriuretic peptide levels (p = 0.003). Both COMPERA 2.0 and REVEAL Lite 2 scores showed a consistent shift toward lower-risk categories. A strong concordance between the two tools was observed. Conclusions: Sequential add-on ERA + PDE5i therapy was associated with meaningful improvement in risk stratification among patients with Group 1.4 PAH. These findings support the clinical utility of simplified, noninvasive risk assessment tools in real-world settings, particularly in resource-constrained environments. Full article

The discharge of metal-containing effluents into aquatic systems remains a major environmental concern because metal ions can persist in water bodies and accumulate in biological systems, potentially affecting ecosystem and human health. Among these contaminants, Cr(III) is frequently encountered in waste streams generated by industrial activities, making its removal an important objective in water quality management. This study investigated the adsorption behavior of Cr(III) using lignocellulosic biosorbents obtained from tamarind shell (Tamarindus indica) after water, H₂O₂, and HCl pretreatments, with particular emphasis on equilibrium behavior, thermodynamic characteristics, and pretreatment-induced physicochemical modifications. Batch adsorption experiments were conducted to evaluate equilibrium behavior. The highest adsorption capacity (41.6 mg g⁻¹) was obtained with the water-treated biosorbent at 60 °C. The equilibrium data were best represented by the Sips model, suggesting that Cr(III) adsorption occurred on surfaces containing adsorption sites with different energetic characteristics. Thermodynamic analysis revealed that the adsorption process was spontaneous, while the enthalpy changes indicated predominantly endothermic behavior for the pretreated biosorbents. ATR-FTIR, SEM, EDS, and XRD analyses were performed to characterize the biosorbents before and after adsorption. The characterization results indicated that oxygen-containing functional groups, particularly hydroxyl and carbonyl functionalities, were associated with the adsorption process. SEM images showed morphological changes associated with pore occupation, while EDS confirmed chromium adsorption and suggested possible ion-exchange mechanisms. XRD patterns indicated a mainly amorphous structure. The results demonstrated that pretreatment-induced modifications strongly influenced the adsorption performance of tamarind shell. Water pretreatment produced the most favorable adsorption behavior, yielding the highest adsorption capacity among the evaluated biosorbents. The combined interpretation of equilibrium, thermodynamic, and characterization results revealed a close relationship between surface properties and Cr(III) uptake. Full article

The Hippo–Yorkie (Yki) signaling pathway is a conserved regulator of tissue growth, and its dysregulation leads to excessive growth and tumorigenesis. Although several microRNAs (miRNAs) have been implicated in Hippo pathway regulation, how they modulate Yki activity in vivo remains incompletely understood. Here, we identify miR-137 as a suppressor of Yki-driven overgrowth in a Drosophila model. A functional miRNA screen revealed that miR-137 overexpression markedly suppresses Yki-induced eye overgrowth, whereas inhibition of miR-137 enhances eye overgrowth phenotypes. Through bioinformatic prediction and genetic screening, we identified Drep1 as a candidate downstream factor associated with miR-137 function. RNAi-mediated depletion of Drep1 phenocopies the suppressive effects of miR-137, whereas Drep1 overexpression enhances Yki-driven tissue overgrowth and proliferation. Consistent with these phenotypes, miR-137 overexpression or Drep1 depletion reduces the expression of canonical Yki target genes, including Diap1 and Expanded, indicating decreased Yki transcriptional output. Importantly, Drep1 knockdown was associated with reduced Yki immunostaining in a complementary wing-disk context, suggesting a potential link between Drep1 and Yki-associated signaling. Consistent with this, miR-137 also reduced the expression of ICAD, the mammalian homolog of Drep1, providing preliminary evidence that miR-137 may regulate ICAD expression in mammalian cells. Together, these findings support a potential regulatory relationship between miR-137 and Drep1 that modulates Yki-driven eye overgrowth and reveal an additional layer of Hippo pathway regulation in vivo. Full article

Maternal exposure to airborne particulate matter smaller than $2.5$ μm (${\mathrm{PM}}_{2.5}$) has been associated with adverse fetal outcomes, although its effects on intramembranous ossification remain poorly understood. This study evaluated the impact of gestational and pregestational exposure to wood-smoke-derived ${\mathrm{PM}}_{2.5}$ on fetal neurocranial ossification in Sprague–Dawley rats. Females were allocated to four exposure conditions combining filtered air (FA) and non-filtered air (NFA): FA/FA, FA/NFA, NFA/FA, and NFA/NFA. Fetuses were collected at gestational day 21 and analyzed using fetal morphometry, radiography, micro-computed tomography, whole-mount alizarin red skeletal staining, histology, and immunohistochemistry for HIF-1$\alpha$, COL-1, BMP-2, FGF-R1, and TGF-$\beta$. Continuous exposure (NFA/NFA) was associated with reduced fetal weight, shorter crown–rump length, impaired craniofacial mineralization, widened cranial sutural regions, and reduced mineral density, particularly in the occipital and interparietal bones. Histologically, exposed fetuses exhibited abundant osteoid, reduced osteocyte incorporation, and diffuse osteoblastic distribution, consistent with delayed osteogenic maturation. Immunohistochemistry showed increased HIF-1$\alpha$ immunoreactivity, altered TGF-$\beta$ regulation, and reduced COL-1 expression in continuously exposed fetuses, whereas BMP-2 and FGF-R1 showed no significant changes. These findings suggest that maternal exposure to wood-smoke-derived PM_2.5 is associated with delayed fetal neurocranial intramembranous ossification, particularly under continuous exposure. The observed immunohistochemical profile, elevated HIF-1$\alpha$, reduced COL-I, and altered TGF-$\beta$, is consistent with a hypoxia-associated imbalance between extracellular matrix deposition and mineral maturation; however, the underlying mechanistic pathway was not directly functionally tested and should be regarded as a biologically plausible inferential model requiring further experimental validation. Full article

Background: Given the increasing consumption of ultra-processed foods (UPFs) and the public health importance of cognitive decline in ageing, understanding how UPFs impact cognitive performance is highly relevant. However, evidence in older adults - particularly in Italy—remains scarce, despite the country’s rapidly ageing population, its comparatively low UPF intake, and its distinct Mediterranean dietary context. Methods: We analysed cross-sectional data from 809 community-dwelling adults aged ≥ 65 years (59.4% women) participating in the NutBrain population-based cohort. Dietary intake was assessed using a 102-item semi-quantitative food frequency questionnaire, and daily grams of foods were classified according to the NOVA system into groups, which were analysed using a compositional data analysis approach. Global cognition and domain-specific performance were measured using standardised neuropsychological tests. Associations between NOVA groups and cognitive outcomes were estimated using multiple linear regression models adjusted for potential confounders. Gender-stratified analyses were also performed. Results: UPFs accounted for 21% of total energy intake, with bakery products as the main contributors. A relative increase of unprocessed or minimally processed foods was associated with better cognitive function (B = 0.36, p = 0.014), whereas a greater contribution of UPFs relative to the overall diet was associated with worse global cognitive function (B = −0.26, p = 0.003). The strongest associations were observed for episodic memory, particularly among women. Conclusions: A higher relative consumption of UPF was associated with worse global and memory-related cognitive performance. Longitudinal and experimental studies are warranted to clarify causality and underlying mechanisms. Full article

The brain maintains homeostasis partially by scavenging waste products. Failure of this function is closely associated with the onset and pathogenesis of various brain diseases, such as Alzheimer’s disease, sleep disorder, and the delay of the reparative process after brain injuries. We recently demonstrated that brain pericytes (BPCs) are sources of lipocalin-type prostaglandin D synthase (L-PGDS), a waste scavenger, in the brain. Based on the above, chemical compounds which promote L-PGDS production could have potential against brain diseases, such as dementia, sleep disorders, and brain injuries. However, the specific chemical compounds that may enhance L-PGDS production in BPCs have not yet been identified. In this study, we explored 158 chemical compounds from FDA-approved drug libraries with these activities. qPCR analysis showed that mirtazapine (MTZ), a noradrenergic and specific serotonergic antidepressant, can increase L-PGDS expression in BPCs as well as in mouse- (m-BPCs) and human-derived BPCs (h-BPCs) in a dose-dependent manner. Since L-PGDS is a secretory protein, m-BPCs and h-BPCs were treated with various MTZ doses and L-PGDS levels in the culture supernatant were investigated. Western blot analysis showed that L-PGDS levels were significantly increased in a dose-dependent manner in both cell types, indicating that MTZ promoted L-PGDS secretion from m-BPCs and h-BPCs. Thus, MTZ may have the potential to be applied as drug repositioning for various brain diseases other than depression by activating L-PGDS production in BPCs, highlighting the importance of BPCs as the source to maintain brain homeostasis. Full article

Circulating ketone bodies (KBs), particularly β-hydroxybutyrate (β-HB), have emerged as metabolites with dual roles as both oxidative fuels and metabolic signaling molecules. Beyond serving as an alternative energy substrate, β-HB regulates diverse pathways involved in oxidative stress, inflammation, and mitochondrial function. However, the clinical implications of circulating KBs remain uncertain. This review summarizes current evidence regarding the potential role of KBs in glycemic progression and diabetic cardiomyopathy (DCM). Epidemiologic and experimental studies report conflicting associations between KB levels and the progression to hyperglycemia or type 2 diabetes, with some findings suggesting that elevated KB levels may reflect a metabolically favorable phenotype or a compensatory mechanism, whereas others indicate links to worsening glycemia. Similarly, studies in DCM have produced divergent results, with β-HB reported to improve mitochondrial function and cardiac performance in some models while contributing to metabolic inflexibility and adverse cardiac remodeling in others. We discuss potential mechanisms underlying these discrepancies and propose that the metabolic effects of β-HB are context-dependent, influenced by factors such as circulating concentration, the mode of ketosis induction, and the underlying metabolic or disease stage. Understanding these contextual determinants may help clarify whether β-HB represents an adaptive metabolic signal or a maladaptive substrate shift in cardiometabolic disease. Full article