Search Results (2,229)

Fine particulate matter (PM_2.5) poses a significant global environmental health threat and is closely associated with diseases across multiple organ systems. This review systematically summarizes the toxic effects and underlying mechanisms of PM_2.5 in the respiratory, cardiovascular, nervous, immune, endocrine, digestive, and genitourinary systems. Key pathogenic processes involve shared pathways such as oxidative stress, inflammatory responses, endoplasmic reticulum stress, autophagy, and apoptosis, along with the activation of system-specific signaling networks. The complex composition and notable spatiotemporal variability of PM_2.5 present challenges for assessing its health risks and clarifying its mechanisms. Moving forward, integrating multi-omics and molecular epidemiology approaches will be essential to unravel its multi-system pathogenic networks and support the development of effective intervention strategies. Full article

Current diagnostic assessments of lung disease rely primarily on medical imaging and global pulmonary function tests, which either provide static structural information or collapse complex regional behavior into global indices. As a result, important information about regional mechanical heterogeneity and early pathological changes may remain inaccessible. In this work, we introduce a conceptual diagnostic framework for the lung based on mechanical system identification and evaluate its feasibility using simulation-based analysis. Rather than directly imaging internal lung structure, the lung–thorax system is treated as an identifiable viscoelastic dynamical system whose internal mechanical properties can be inferred from its response to controlled external excitation. A multi-degree-of-freedom mechanical representation of the lung was developed to capture the dominant low-frequency behavior of the chest wall and major lung regions. Sensitivity and Fisher-information analysis confirmed the structural identifiability of regional stiffness parameters (FIM eigenvalues λ₁ = 1.75 × 10⁻⁹ and λ₂ = 8.91 × 10⁻¹⁰). Inverse fitting experiments accurately recovered simulated stiffness perturbations (e.g., k₀₁ = 240 → 239.5; k₀₂ = 154 → 159.5) from noisy frequency response data, while classification experiments achieved the complete separation of simulated pathological configurations in an idealized synthetic scenario, supporting theoretical discriminability rather than clinical performance claims. These findings demonstrate the theoretical feasibility of a diagnostic paradigm in which regional lung mechanical alterations can in principle be identified through mechanical system identification rather than direct imaging, thereby suggesting a complementary approach for a non-invasive assessment of regional lung mechanics from externally measured responses. By quantifying regional stiffness and mechanical heterogeneity, this framework may also support the personalization and monitoring of pulmonary rehabilitation strategies in chronic respiratory disease. Full article

Introduction: Ubiquinol–cytochrome c reductase core protein II (UQCRC2) encodes a core subunit of the mitochondrial electron transport chain (ETC) complex III (CIII). Biallelic pathogenic variants in UQCRC2 have been associated with mitochondrial disease characterized by lactic acidosis, developmental delay, hepatopathy, and episodic metabolic decompensation. Methods: We reviewed the biochemical phenotypes of 14 individuals possessing UQCRC2 variants, including two novel cases. We performed biochemical studies of mitochondrial respiration and oxidative phosphorylation (OXPHOS) complex measurements in patient-derived fibroblasts. Results: We report reduced CIII activity in a majority of individuals possessing variants in UQCRC2, as well as biochemical findings consistent with impaired mitochondrial energy metabolism, though impairments in mitochondrial respiration were variable. The two previously unreported, unrelated patients possessing the likely pathogenic missense variant c.361T>C, p.Tyr121His in UQCRC2 in trans with a 16p12.2 microdeletion encompassing UQCRC2 showed milder phenotypes, less severe metabolic decompensations, and no long-term neurological impairments. Both individuals display reduced CIII activity and mitochondrial respiratory dysfunction. Discussion: These data expand the current understanding of genotypes associated with UQCRC2-associated mitochondrial disease to include the novel 16p12.2 microdeletion. These data also highlight the consistent biochemical phenotype associated with UQCRC2-associated mitochondrial disease, and the need for consistent biochemical and respiratory assessment of individuals possessing UQCRC2 variants to further our understanding of this phenotype. Full article

Background: Breaststroke performance in young swimmers is influenced by a complex interaction of anthropometric, physiological, and technical factors. However, existing studies predominantly focus on pre-selected or elite youth swimmers, limiting insight into performance development in non-elite populations without early selection bias. Purpose: This study aimed to identify key predictors of 50-m breaststroke performance and to examine longitudinal changes in selected characteristics in pre-adolescent, non-elite female swimmers. Methods: Fourteen female swimmers (baseline biological age: 10.52 ± 0.37 years) who entered swimming training without prior anthropometric or physiological selection were followed over three consecutive years. Measurements were collected at six time points and included anthropometric dimensions, body composition, aerobic and anaerobic capacity, respiratory volumes, and 50-m breaststroke performance. This investigation was a prospective longitudinal cohort study. Data were analysed using generalised estimating equations. Results: The correlation-filtered model explained 76% of the variance in 50-m breaststroke time. Chest depth (B = −0.16, p = 0.03), foot length (B = −0.17, p = 0.04), foot width (B = 0.30, p < 0.001), and shoulder width (B = −0.07, p = 0.04) emerged as significant anthropometric predictors. Maximal oxygen uptake also showed a significant association with performance (B = −0.33, p = 0.02). Conclusions: In pre-adolescent, non-elite female swimmers, selected anthropometric characteristics—particularly trunk dimensions and foot morphology—are associated with short-distance breaststroke performance. Aerobic capacity appears to play an indirect, supportive role. These findings highlight the importance of longitudinal monitoring without early selection and support a development-oriented approach to youth swimming training. Full article

Background and Clinical Significance: Mucopolysaccharidosis type VI is a rare lysosomal storage disorder due to arylsulfatase B enzyme deficiency, leading to progressive multisystem disease and complex airway. Acute respiratory infections can precipitate airway embarrassment. A structured treatment guideline is currently lacking. We present a 7-year-old MPS VI male with respiratory distress, highlighting the challenges in management. Case Presentation: Case review focusing on clinical presentation, imaging findings, and multidisciplinary decision-making during acute deterioration. A child diagnosed with MPS VI at the age of 3.5 years old, due to low arylsulfatase B enzyme activity and homozygous for c.275C>A p.(Thr92Lys) variant in the ARSB gene. At 7 years of age, he showed the signs of dyspnoea, increased respiratory effort with bilateral crepitations, and noisy breathing. Initial management included facemask oxygen, nebulised adrenaline, corticosteroids, and bronchodilators. Computer tomography scan of the neck and chest showed a complex upper airway, multiple tracheal narrowing, tortuosity, and an extra loop of truncus brachiocephalicus from the arch of the aorta. Potential interventions carried substantial risks due to abnormal airway and multisystem disease. Following extensive multidisciplinary discussion after careful consideration of the significant risks associated with invasive airway interventions, a shared decision was reached with the family to adopt a comfort-focused palliative care approach. Despite the best supportive care, the child unfortunately passed away after 3 months. The family was involved in every decision process and was fully supported. Conclusions: MPS VI is associated with complex airways and multisystem disease. Multidisciplinary decision-making with family is critical to safe and appropriate care. The rarity of the disease, lack of guidelines, complex airways, and multiple comorbidities make management challenging. Full article

Background/Objectives: Damage Control Resuscitation (DCR) is a critical strategy in the management of severe trauma, focusing on the optimisation of the patient’s physiological condition. This study reviews current DCR strategies, emphasizing the mitigation of the “diamond of death”—hypothermia, acidosis, coagulopathy, and hypocalcemia—while addressing complex disturbances like respiratory distress syndrome (ARDS) and (acute kidney injury) AKI in high-ISS (Injury Severity Score) patients. Methods: A systematic review of 59 contemporary sources was conducted, encompassing clinical trials (e.g., CRASH-2), military-to-civilian protocol translations, and guidelines from the C and European Resuscitation Council. The analysis focused on pre-hospital interventions, in-hospital transfusion protocols, and the impact of transport logistics on survival. Results: Evidence highlights that aggressive crystalloid resuscitation (over 5 L) significantly increases mortality, favoring balanced blood component therapy (1:1:1 ratio) or Whole Blood guided by viscoelastic testing like rotational thromboelastometry (ROTEM) or thromboelastography (TEG). Pre-hospital success is driven by rapid hemorrhage control via tourniquets, early administration of Tranexamic Acid (TXA), no aggressive crystalloids, permissive hypotension, proactive calcium supplementation is recommended in early care. Furthermore, the integration of Helicopter Emergency Medical Services (HEMS) is independently associated with improved survival in multi-organ trauma by reducing time to definitive care and facilitating “en-route” damage control. Conclusions: The evolution of rescue strategies focused on mitigating the effects of the diamond of death, combined with the implementation of permissive hypotension and optimized HEMS logistics, constitutes the foundation of a modern model aimed at minimizing mortality in multi-organ trauma. Full article

Maternal vaccination against respiratory syncytial virus (RSV) represents a major advance in early-life infection prevention. Although clinical efficacy and early real-world effectiveness are well established, sustained population-level impact depends on equitable uptake. This review synthesizes determinants influencing maternal RSV vaccination within the evolving dual-strategy landscape that includes both maternal vaccination and infant monoclonal antibody prophylaxis. A structured narrative review was conducted following PRISMA principles. PubMed/MEDLINE and Google Scholar were searched for studies published between January 2022 and February 2026. Eligible studies examined behavioral, interpersonal, structural, economic, and policy determinants of maternal RSV vaccination uptake, as well as early implementation and modelling evidence. Findings were integrated within a multilevel analytical framework. Maternal uptake is shaped by interacting determinants across individual, healthcare provider, and health system domains. Key drivers include perceived infant disease severity, vaccine safety confidence, perceived effectiveness, and prior antenatal vaccination behavior. Healthcare provider recommendation consistently emerges as the strongest facilitator. Coverage variability reflects differences in reimbursement, antenatal care integration, and national policy endorsement. The coexistence of maternal vaccination and infant monoclonal antibody strategies introduces additional comparative decision-making complexity. Early implementation data indicate heterogeneous uptake and socioeconomic gradients, while modelling demonstrates sensitivity to coverage, timing, epidemiology, and cost. Translating biological efficacy into sustained public health benefit requires coordinated behavioral, structural, and policy strategies, strong provider engagement, and context-sensitive implementation frameworks to ensure equitable coverage. Full article

Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular–endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD. Full article

Complex I (NADH:quinone oxidoreductase, CI) is central to cellular aerobic energy metabolism. The L-shaped structure of CI is unique, where the hydrophilic arm is responsible for the electron transfer function and the membrane arm operates proton pumping. These two functional sites are spatially far apart yet functionally connected. This basic core subunit architecture is highly conserved from bacterial to mammalian CI. Here, to gain detailed mechanistic insight into the role of the membrane subunit ND2 in the coupling mechanism, we mutated several highly conserved residues in the middle of the membrane axis of NuoN, the E. coli CI homolog of ND2. To more precisely investigate the consequences of mutational effects on highly conserved residues, we purified each mutant CI and compared the mutational effects on electron transfer and proton pumping activity using our instant membrane reconstitution method with E. coli double knockout (DKO) membrane vesicles lacking both CI and alternative NADH dehydrogenase (NDH-2). Thre results were corroborated by conventional proteoliposome reconstitution experiments. We found that Lys247 and Lys395 are absolutely essential for both electron transfer and proton pumping activities, while about 50% reduction of NADH oxidase activity but no reduction in proton pumping activity was observed in Lys217, and no significant decrease was detected in Glu133. Furthermore, unexpectedly, we were able to purify an NuoN knockout (ΔNuoN) mutant, which contained stoichiometric peripheral subunits NuoB, NuoCD, NuoE, NuoF, NuoG, and NuoI; and a substoichiometric amount of NuoH and a reduced amount of quinone. However, surprisingly, this isolated ΔNuoN CI showed CI activities (~30% of the WT) after being reconstituted into DKO membranes but not into proteoliposomes. Later, we confirmed by blue native PAGE that the wild-type CI was partially formed from ΔNuoN CI by recruiting its missing membrane subunits that existed in DKO membranes. Our data strongly suggest that ND2/NuoN plays an essential role in the coupling mechanism in CI. CI is the entry respiratory chain enzyme and is central to cellular energy metabolism. Two highly conserved lysine residues in the center of the antiporter-like membrane subunit ND2 are essential for the coupling mechanism between electron transfer and proton translocation. Full article

Metagenomic and targeted next-generation sequencing (NGS) technologies are rapidly transforming diagnosis and management for infectious diseases. This review comprehensively examines the current applications of metagenomic NGS (mNGS) and targeted NGS (tNGS) in clinical microbiology, highlighting their roles in pathogen detection, antimicrobial resistance profiling, virulence characterization, and outbreak investigation—particularly in complex cases such as pneumonia, critical illness with pulmonary infections, and pediatric acute respiratory illnesses. We discuss the diagnostic performance, advantages, and limitations of these approaches, including challenges related to sensitivity, specificity, standardization, bioinformatic complexity, and cost-effectiveness. Furthermore, we explore emerging opportunities for integrating NGS-based surveillance with public health strategies, such as wastewater epidemiology, to monitor healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) at the population level. Finally, we outline key steps needed to translate these powerful genomic tools from research settings into routine clinical and public health practice. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by irreversible fibrosis. Aberrant cell differentiation plays a crucial role in the development of IPF. Although recent studies have suggested that mitochondrial dysfunction may play a role in IPF, its direct impact on fibrosis remains unclear. This study aimed to clarify the role of mitochondria in lung cell differentiation and pulmonary fibrosis development by employing mito-mice ND6^M, in which the activity of respiratory chain complex I is decreased due to a mitochondrial DNA mutation (G13997A). Pulmonary fibrosis was induced by administering bleomycin (BLM) to both wild-type and mito-mice ND6^M. Bone marrow-derived macrophages and primary lung fibroblasts, generated from both types of mice, were analyzed to evaluate M1/M2 polarization and myofibroblast differentiation, respectively. Compared to wild-type mice, mito-mice ND6^M exhibited more severe fibrosis and lower survival rates following BLM inoculation. Lactate production in the lungs after BLM administration was significantly higher in mito-mice ND6^M than in wild-type mice. TGF-β1-treated fibroblasts from mito-mice ND6^M exhibited increased α-smooth muscle actin expression. While type I collagen expression was not different between these mice, TGF-β1-induced expression of phosphoserine phosphatase and serine hydroxymethyltransferase2, two of the enzymes involved in the serine–glycine pathway, was significantly higher in mito-mice ND6^M than in wild-type mice. On the other hand, mitochondrial dysfunction had a small effect on pulmonary inflammation and on M1/M2 macrophage polarization. In conclusion, mitochondrial dysfunction promotes TGF-β1-induced myofibroblast differentiation and BLM-induced pulmonary fibrosis. Mitochondria-dependent metabolic reprogramming may therefore represent a promising therapeutic target in IPF. Full article

The efficient delivery of small interfering RNAs (siRNAs) to immune and respiratory cells represents a key methodological challenge in developing inhaled RNA interference (RNAi) approaches. A central question is whether siRNA functionality is preserved following aerosolization, as the mechanical stress of nebulization may compromise siRNA integrity and silencing activity. Here, we report a proof-of-concept study using THP-1-derived macrophage-like cells as a tractable in vitro model to characterize jet nebulization for siRNA delivery. Three siRNA candidates targeting interleukin-1 beta (IL-1β) were computationally designed and validated for potent silencing activity and low cytotoxicity. Using a commercially available, off-the-shelf jet nebulizer combined with Lipofectamine RNAiMAX, we demonstrate that siRNA-lipoplexes retain their gene-silencing activity after aerosolization, achieving robust IL-1β knockdown. The delivery efficiency was influenced by siRNA-lipoplex complexation, highlighting the importance of formulation parameters. These findings establish a practical and accessible in vitro platform for evaluating nebulized siRNA functionality, providing a foundation for future studies in more complex and physiologically relevant airway models. Full article

The integration of immersive educational technologies into medical education has attracted growing attention owing to their potential to improve the learning of complex anatomical structures and specialized terminology. This study investigates the use of zSpace technology as an interactive, learner-centered instructional tool for teaching the human respiratory system to undergraduate students in Nursing, Midwifery, and Physician Assistant programs. A structured pedagogical framework combined prior theoretical instruction in anatomy and Latin medical terminology with a zSpace-based practical learning activity was used. After the workshop, the students completed a survey evaluating perceived learning effectiveness, student engagement, and the quality of three-dimensional (3D) visualization. Data from 34 participants were analyzed using descriptive statistics and reliability analysis. The results indicated high levels of student satisfaction regarding the clarity, anatomical detail, and educational value of the immersive 3D models, along with higher levels of engagement compared with traditional methods. Despite challenges related to technical infrastructure, lecturer readiness, and students’ digital competencies, the findings support the pedagogical relevance of immersive 3D technologies in medical education. Overall, the findings suggest that students perceive zSpace technology as supporting anatomical understanding and enhancing engagement within the studied context. Full article

This study investigated the preservative effect and molecular mechanism of cold-air pre-cooling (CAP) combined with storage at 15 °C/85% relative humidity on Volvariella volvacea. CAP significantly reduced weight loss and browning, maintained moderate respiratory intensity, minimised malondialdehyde accumulation and polyphenol oxidase activity, and preserved higher firmness and soluble-protein content, extending the shelf life by 4 d. An analysis of energy metabolism indices revealed that CAP increased mitochondrial quantity, membrane potential, and ATP content. Specifically, CAP restricted the tricarboxylic acid (TCA) cycle rate by downregulating the activities of succinate dehydrogenase, isocitrate dehydrogenase, and citrate synthase. Additionally, CAP prevented the peak activation of respiratory complex I, while sustaining optimal activity of complexes III and IV, thereby stabilising intracellular ATP levels. Transcriptomic analysis further indicated that CAP suppressed the activity of the TCA cycle and oxidative phosphorylation pathways during postharvest storage. Quantitative real-time PCR (qPCR) validated the downregulation of genes associated with respiratory complexes after CAP treatment. In conclusion, CAP maintained the postharvest quality of V. volvacea by preserving energy metabolism homeostasis, providing a theoretical basis for its application in edible mushroom preservation. Full article

Background: The control of fleas and ticks in companion animals is a persistent challenge with animal welfare and public health implications. The increasing resistance to antiparasitic treatments, coupled with concerns over the environmental impact and non-target effects of synthetic acaricides, has driven interest in sustainable alternatives. Essential oils (EOs) have emerged as potential candidates due to their complex chemistry and modes of action. Methods: This review critically analyzes the scientific literature on essential oils for ectoparasite control in companion animals. Specifically, it examines their chemical composition, multi-target mechanisms of action, laboratory and field efficacy, role in resistance mitigation, and integration into IPM strategies. Results: Several EOs, particularly those rich in phenolic compounds (thymol, carvacrol, eugenol, and cinnamaldehyde), demonstrate promising in vitro insecticidal and acaricidal activity. Their multi-target mechanisms, affecting neuronal, respiratory, and cuticular functions, not only provide efficacy but also represent a significant barrier to rapid resistance development. However, their translation to reliable field performance is hampered by high volatility, formulation instability, and innate variability. Conclusions: EOs represent a valuable source of bioactive compounds for reducing reliance on conventional acaricides and can play a key role within IPM strategies. To realize their full potential in mitigating resistance, focused advancements are needed in standardized testing, formulation science to enhance stability and residual activity, and rigorous field studies to confirm safety and efficacy. Full article