Search Results (5,325)

Laryngeal adductor breathing dystonia (LABD) is a rare form of focal, task-specific respiratory dystonia affecting the laryngeal muscles of unknown aetiology. Unlike classical laryngeal dystonia (spasmodic dysphonia), LABD is not primarily characterised by impaired speech, but rather by dysfunction of respiratory laryngeal control. The hallmark pathophysiological alteration consists of involuntary, action-induced adductor spasms of the laryngeal muscles during respiration, particularly during inspiration. LABD must be distinguished from inducible laryngeal obstruction (ILO), a broader, heterogeneous condition encompassing episodic, stimulus-triggered supraglottic or glottic closure, associated with asthma, reflux, or psychological triggers, that is generally not task-specific and lacks the neurological substrate characteristic of dystonia. In contrast, LABD is a persistent, effort-dependent, neurologically driven dystonia, demonstrable by paradoxical adductor spasms on fibreoptic laryngoscopy during normal inspiration and confirmed electromyographically by paradoxical thyroarytenoid muscle activation instead of the expected inspiratory relaxation. Traditional treatments, including respiratory retraining, speech therapy, biofeedback, psychotherapy, benzodiazepines, dopamine-blocking agents, and anticholinergic drugs, have proved largely ineffective. Tracheostomy may be required in cases of severe respiratory compromise. Botulinum toxin type A (BoNT/A) injections have been reported to successfully reduce inspiratory stridor in selected patients. Here, we present three cases of LABD displaying distinct phenotypes, in which typical features were associated with involvement of extra-laryngeal cranial districts, further expanding the known phenotypic spectrum of this condition. Full article

Background/Objectives: Accurate tissue diagnosis of small pulmonary nodules remains technically challenging with conventional bronchoscopic techniques. Radial probe endobronchial ultrasound-guided transbronchial lung cryobiopsy (RP-EBUS–guided TBLC) with a guide sheath (GS) may improve diagnostic yield; however, target instability during cryobiopsy remains a limitation. We aimed to evaluate the diagnostic yield of RP-EBUS-guided TBLC with a GS for pulmonary nodules < 3 cm that were suspected of malignancy. Methods: This retrospective observational study included patients who underwent RP-EBUS-guided TBLC with a GS for lung lesions suspected of malignancy on computed tomography between 1 February 2024 and 31 December 2025 in South Korea. After the target lesion was identified, the bronchoscope was inserted and fixed within the segment; its position was maintained while RP-EBUS was withdrawn, and lesion stability during respiration was confirmed. Results: A total of 99 patients were included in the final analysis. After patients with an indeterminate diagnosis were excluded, the final diagnostic yield was 83.2%. The sensitivity and specificity were 78.9% and 100.0%, respectively. Pneumothorax occurred in 6.0% (6/99) of patients. Bleeding of grade 3 or higher was observed in two patients, and a Fogarty balloon catheter was preemptively used in five patients at the operator’s discretion. In multivariable logistic regression analysis, the computed tomography bronchus sign was identified as the only significant factor associated with pathological confirmation (odds ratio, 6.090; p = 0.005). Conclusions: RP-EBUS-guided TBLC with a GS provided an acceptable diagnostic yield and safety profile, even in small pulmonary nodules < 3 cm. Full article

Proper handling during harvesting and subsequent postharvest management is essential to reduce losses in fruits and vegetables, particularly because these products remain metabolically active after harvest. Physiological processes such as respiration, transpiration, ethylene production, softening, physiological disorders, and postharvest diseases determine quality deterioration, shelf life, and marketability. However, these processes do not affect all commodities in the same way; for example, climacteric fruits are strongly influenced by ethylene during ripening, whereas non-climacteric fruits generally show lower ethylene production and different postharvest behavior. In Mexico, postharvest management is especially relevant because fruit and vegetable producers differ widely in terms of production scale, infrastructure, access to technology, financing capacity, and market destination. Producers with limited access to technology require practical and low-cost alternatives, while more technologically advanced producers may use specialized systems but still experience postharvest losses due to physiological deterioration, handling conditions, logistics, and market constraints. Therefore, this review summarizes the main postharvest physiological processes affecting fruits and vegetables and discusses their implications for knowledge transfer, technology adoption, and sustainability among local producers in Mexico. The review highlights that reducing postharvest losses requires commodity-specific management, continuous technical support, low-cost and locally adaptable technologies, and coordinated participation among researchers, extension personnel, producers, government institutions, industry, and market actors. Strengthening postharvest knowledge transfer to small and local producers is essential to reduce losses, improve marketability, and promote more sustainable fruit and vegetable systems in Mexico. Full article

Mosquito control personnel work within health departments, public works, private companies, and other agencies. These essential outdoor workers have highly specialized training and are faced with a variety of potential health and safety hazards (e.g., arthropod bites and stings, exposure to insecticides and other chemicals, working with heavy equipment, noise, heat, solar ultraviolet radiation, slips, trips, and/or falls). Mosquito control personnel undergo employer-provided and other types of training on a variety of topics from regulatory updates to new surveillance and control techniques that are required for safety purposes and to maintain their applicator license. Here, an exploratory baseline survey was conducted among members of the North Carolina Mosquito and Vector Control Association (NCMVCA) and the Virginia Mosquito Control Association (VMCA). There was a 28% response rate so results should be interpreted with caution in this pilot study. Most respondents reported utilizing ultra-low volume insecticide application equipment for controlling adult mosquitoes. Backpack sprayers were utilized by less than half of respondents. Those who reported using respirators showed higher concern about insecticide-related health effects than those who did not use respirators. Outdoor workers encounter various potential hazards and utilize several forms of personal protective equipment to reduce risks. This baseline work can be considered a starting point for implementing and strengthening occupational safety and health awareness and preventive measures for mosquito control workers. Knowledge of health and safety hazards can reduce workplace risk. Full article

Biokinetic complexities (plastic sorption, protein binding, and cellular accumulation) may cause large discrepancies between nominal and biologically effective concentrations of test compounds assessed by new approach methods (NAMs). This case study was performed to explore a generally applicable workflow that addresses biokinetic complexities in the context of NAM-based hazard testing for next-generation risk assessment (NGRA). The pesticide tebufenpyrad (TEBU) is a challenging test compound, as it (i) is hydrophobic, (ii) has an intracellular target (mitochondrial respiration), and (iii) is acting at low concentrations (susceptible to biokinetic complexities). In the newly established NeuriTox-M neurotoxicity assay, based on human dopaminergic (LUHMES) neuron cultures, TEBU showed toxic effects at 20 nM. Mass spectrometric analyses of various experimental setups showed that a large fraction (75% to >90%) of TEBU was adsorbed to plastic. This effect was strongly attenuated by albumin in the medium. Cells, cultured on plastic, were considered unsuitable to assess cellular uptake. Therefore, alternatives were explored: when cells were used as suspension cultures (3% v/v) in albumin-containing medium, analysis worked best. Under such conditions, the concentration ratio (cells/medium) of TEBU was around 10. Data from an in vitro distribution (VIVD) model were in good agreement with the measurements. VIVD predicted the unbound medium TEBU concentration (C_u) to be 2–3 orders of magnitude below the nominal concentration and the total cellular concentration to be 10–100-fold above. Standard cell culture assays showed that the medium albumin content indeed altered the TEBU toxicity threshold. More such studies are needed to embed biokinetics information into NGRA. Full article

Background: While traditional pasture-based systems offer sheep natural living conditions and freedom, barn farming provides greater environmental control and protection. The choice of farming system is a crucial factor directly affecting the physical and mental health of the animals. Aim: This study evaluated welfare indicators and parasite prevalence in different sheep management systems, examining the impact of parasitic infections on ewe welfare. Methods: Conducted from November 2025 to April 2026 across 26 farms (13 confined and 13 pasture), the study individually assessed a sample of 1192 ewes aged 2–7 years. Animal-based welfare indicators were assessed using the AWIN protocol for sheep, while parasitic infections were determined from fecal sampling. Results: The results revealed significant differences (p < 0.001) between the systems. Pasture farms showed a higher prevalence of soiled fleece (60.14%), skin lesions, ocular and nasal discharge (6.35%; 31.22%), respiratory issues (16.75%), fecal soiling (16.23%), borderline anemia (16.23%), and excessive itching (16.23%). In contrast, confined systems exhibited higher prevalence of fleece loss (36.00%), hoof overgrowth (20.96%), udder asymmetry (1.44%), and wool pulling (8.32%). Identified parasites included Eimeria spp., gastrointestinal strongyles, Trichuris ovis, Dictyocaulus filarial, Muellerius capillaris, Protostrongylus rufescens, Moniezia spp., Dicrocoelium dendriticum, Fasciola hepatica, Paramphistomum spp., and Giardia intestinalis. Significant correlations (p < 0.001) were found between certain welfare indicators and parasite infections in confined systems, such as between thin body condition score and Eimeria spp., and between fleece quality and fecal soiling with gastrointestinal strongyles, while in pasture systems, thin BCS, nasal discharge, and respiration quality correlated with Muellerius capillaris, borderline anemia with Trichuris ovis and Dictyocaulus filaria, and fecal soiling with Eimeria spp. and Dicrocoelium dendriticum. Conclusions: This data underscores the critical need to improve ewe welfare and implement targeted parasite control strategies in both farming systems. Full article

Quantum machine learning (QML) provides a framework for benchmarking wearable biosignal classification relevant to stress detection. Motivated by the burden of stress-related conditions, this study compares three quantum classifiers with seven classical baselines using heart rate and respiration rate features as inputs under noise-free and noisy conditions. Uncertainty was quantified using Nadeau–Bengio-corrected confidence intervals and percentile bootstrap ($B=1000$). The variational quantum classifier (VQC) achieved an accuracy of $99.47\%/97.30\%$ (noise-free/noisy), the quantum support vector classifier (QSVC) achieved $99.90\%/99.37\%$, and PegasosQSVC achieved $99.80\%/99.70\%$. Additionally, under the assessed proof-of-concept conditions, statistical equivalence between the QSVC and the best-performing classical model was established at $\Delta =1$ pp; PegasosQSVC under noise achieved equivalence at $\Delta =2$ pp with accuracy degradation of less than $0.10$ pp. The time feature was identified as the primary separability driver in a post hoc classical ablation. Tree-based models were robust on physiological features alone. The surveyed methods provide a reproducible, noise-aware benchmark for wearable physiological signal classification; however, the reported high accuracies are based on a deliberately separable proof-of-concept benchmark and do not demonstrate clinical utility or a quantum advantage. Full article

Tauopathies are a group of neurodegenerative diseases characterized by the accumulation of abnormal tau protein, leading to mitochondrial dysfunction. Because of neurons’ high energy demands, such impairments significantly contribute to neuronal vulnerability. Recent evidence indicates that mitochondria can be transferred between cells to support energy-deficient cells through intercellular mitochondrial transfer (IMT). Given the impact of pathological tau on mitochondrial transport and cytoskeletal dynamics, we hypothesized that IMT is altered in tauopathies. We investigated IMT from astrocytes to neurons, as well as the influence of abnormal tau protein on this process, using co-cultures of SH-SY5Y cells (neuronal model) and A172 cells (astrocytic model). Key data were then confirmed in human iPSC-derived neurons and astrocytes. We show that IMT is enhanced in the presence of abnormal tau and occurs predominantly through contact-dependent mechanisms. Transferred mitochondria were either integrated into the host mitochondrial network, degraded in lysosomes, or remained isolated in the recipient cells’ cytosol. This transfer improved cellular respiration and was associated with increased bioenergetics in pathological cells. Together, our results highlight IMT as a link between tau pathology and neuronal metabolic adaptation, suggesting that this process reflects an endogenous metabolic adaptation holding therapeutic potential to mitigate energy deficits in neurodegenerative diseases. Full article

Metabolic dysfunction and proteinopathy are hallmarks of neurodegenerative disease, yet their mechanistic interplay remains poorly understood. Here, we show that loss of the neuronal NAD⁺-synthesizing enzyme Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) disrupts amyloid precursor protein (APP) processing in cortical neurons, leading to accumulation of APP C-terminal fragments (APP-CTFs). NMNAT2 deficiency lowers the NAD⁺/NADH redox ratio coincident with APP-CTF buildup. Temporal profiling reveals a biphasic increase in APP-CTFs, with an initial gradual rise followed by rapid accumulation, paralleling the expansion of differentially expressed proteins. Pathway analysis indicates early activation of JNK/MAPK signaling, followed by late-stage suppression of mitochondrial pathways and induction of endoplasmic reticulum stress and unfolded protein response programs. Seahorse analyses reveal early glycolytic impairment followed by deficits in mitochondrial respiration. Knockdown of the NAD⁺ hydrolase sterile alpha and TIR motif-containing protein 1 (SARM1) restores mitochondrial function and normalizes APP-CTF levels in NMNAT2 knockout neurons, whereas NAD⁺ supplementation provides only modest rescue. Together, these data demonstrate that neuronal NAD⁺ depletion drives progressive, SARM1-dependent disruption of glucose metabolism and proteostasis, impairing APP processing. The NMNAT2–SARM1 axis thus links metabolic stress to proteinopathy and highlights SARM1 as a central mediator of neurodegenerative dysfunction. Full article

Common bean (Phaseolus vulgaris L.) is a strategic crop whose sustainable production depends on symbiosis with nitrogen-fixing bacteria. However, the composition and functional potential of the nodule microbiome in varieties adapted to semi-arid regions, such as northern Mexico, remain poorly documented. Therefore, this study evaluated the influence of host genotype on nodule-associated bacterial communities in three improved varieties (Pinto Bravo, NOD1, and Jamapa) under conventional management, using high-throughput sequencing of the V3–V4 regions of the 16S rRNA gene. Alpha and beta diversity analyses showed no significant differences among varieties, indicating a similar nodular microbiome regardless of genotype. At the phylum level, Proteobacteria and Bacteroidota predominated, suggesting a conserved microbial core. At the genus level, Rhizobium was the most abundant taxon, while non-rhizobial genera such as Acinetobacter and the JC017 lineage were also detected. Functional prediction using PICRUSt2 revealed conserved metabolic profiles, with dominant pathways associated with amino acid biosynthesis, carbon metabolism, aerobic respiration, and fatty acid biosynthesis, indicating metabolic redundancy linked to tolerance to osmotic, thermal, and oxidative stress. The results suggest that under semi-arid conditions, the symbiotic interaction is governed by mechanisms at the host species level (P. vulgaris), which ensure the recruitment of a functional core microbiome, whereas intraspecific variation among improved varieties may influence the recruitment of specific accessory taxa. Full article

Mediterranean agricultural systems are highly vulnerable to increased climatic variability, which threatens soil water availability and the functionality of the soil carbon (C) cycle. Soil management practices strongly influence water dynamics and C-substrate quality, thus potentially affecting the temperature sensitivity of soil respiration. We evaluated the combined effects of tillage (traditional tillage, TT; reduced tillage, RT), fertilization (mineral, MF; addition of biosolid compost, BC), and rainfall inputs (ambient conditions, C; reduction of 30% rainfall inputs, EX) on soil water content (SWC) and storage (SWS), and in situ soil respiration (Resp) dynamics over three agricultural seasons in a Mediterranean legume–wheat rotation, using a factorial field experiment. We also evaluated how the sensitivity of soil respiration to temperature could be affected by tillage and fertilization types in a complementary laboratory experiment under controlled moisture and temperature conditions. RT was effective in improving SWS and mitigating surface desiccation, although this advantage was attenuated in wet years due to homogenization of moisture along the soil profile. Soil Resp was primarily controlled by SWC. BC stimulated soil respiration mainly during the first crop season, with a residual non-significant trend in the third season. This effect appeared constrained under dry periods, although no significant fertilization × rainfall exclusion interaction was detected. The diurnal cycle of Resp showed a clear decoupling from diurnal soil temperature. Crucially, the intrinsic thermal sensitivity of respiration (Q₁₀) remained stable across all tillage and fertilization treatments, suggesting that field variability is driven by water dynamics and crop phenology and not by microbial responses to changes in substrate availability. Our results confirmed the hierarchical role of climate on C-cycling processes. Full article

Background: Acetaminophen (APAP) overdose remains a major cause of acute liver injury. Although N-acetylcysteine (NAC) is the clinically established antidote for APAP toxicity, its efficacy is greatest when administered early, and additional therapeutic strategies are still needed for patients with delayed presentation or progressive injury. Because APAP hepatotoxicity involves coupled disturbances in redox control, mitochondrial performance, and cellular metabolism, metabolic enzymes that sustain NADPH availability may critically influence disease severity. Malic enzyme 1 (ME1), a cytosolic NADPH-generating enzyme, has not been functionally defined in this context. Methods: To determine the contribution of ME1 to APAP-induced liver injury (AILI), we used hepatocyte-specific ME1 knockout mice, hepatic overexpression and reconstitution approaches, primary mouse hepatocytes, and an enzymatically inactive ME1 mutant. Liver injury and associated changes in oxidative stress, mitochondrial function, energy metabolism, autophagic flux, and endoplasmic reticulum (ER) stress were evaluated using biochemical, histological, molecular, and ultrastructural analyses, together with pharmacological interventions. Results: Genetic loss of ME1 did not substantially alter early APAP metabolic activation-related indices, including APAP-protein adduct formation, but markedly increased hepatocellular metabolic vulnerability after APAP challenge. This phenotype was characterized by enhanced lipid peroxidation, impaired mitochondrial polarization, reduced ATP availability, defective autophagic flux, and amplified ER stress, leading to more severe liver damage. In contrast, ME1 overexpression or reconstitution promoted a more adaptive metabolic response and limited tissue injury. These effects depended largely on ME1 catalytic activity, as protection was markedly weakened with the mutant enzyme. Pharmacological analyses further supported the involvement of AMPK/mTOR-associated autophagy regulation and ER stress adaptation in the downstream actions of ME1. Malic acid also partially attenuated APAP-induced hepatotoxicity in vivo and in vitro. Conclusions: ME1 functions as an endogenous metabolic factor that influences the outcome of APAP-induced liver injury. Its catalytic activity supports hepatocyte survival primarily by preserving reductive capacity, bioenergetic balance, and adaptive stress responses, rather than by altering APAP metabolic activation. Full article

Stress-related psychiatric disorders are frequently associated with impaired mitochondrial function, altered neuronal energy metabolism, and reduced neuroplasticity. Intracellular pathways such as PI3K/Akt and mTOR play central roles in regulating mitochondrial bioenergetics and neuronal structural adaptation. Gelsemium is traditionally used in integrative and homeopathic practice; however, the cellular effects of prolonged exposure to high serial dilutions remain insufficiently characterized. This study aimed to examine the effects of chronic exposure to Gelsemium preparations on mitochondrial function and neuronal plasticity in vitro. Human SH-SY5Y neuroblastoma cells were treated for 14 days with different Gelsemium preparations 9C, 15C, 30C. Mitochondrial bioenergetics, reactive oxygen species (ROS) production, cell viability, neurite outgrowth, and phosphorylation of Akt and mTOR were assessed using complementary biochemical, imaging, and signaling analyses. Chronic exposure to Gelsemium preparations was associated with increased ATP production, increased mitochondrial respiration and glycolytic activity, reduced oxidative stress, improved cell viability, and increased neurite outgrowth compared with untreated controls. These changes were accompanied by increased phosphorylation of Akt and mTOR. The convergence of bioenergetic, redox, morphological, and signaling readouts suggests a coordinated cellular response under prolonged exposure conditions. These findings indicate that chronic exposure to Gelsemium preparations (9C, 15C, 30C) is associated with coordinated changes in mitochondrial bioenergetics, redox balance, and Akt/mTOR signaling in neuronal cells under in vitro conditions. Full article

Background/Objectives: Signaling mediators of PPARγ influence pathways involved in adipogenesis, lipid storage, inflammation, energy-related processes, and glucose utilization. Recent research indicates that PPARγ coregulators, recruited or released during ligand binding, govern specific gene pathways. It was recently discovered that Gα_q, a heterotrimeric G protein subunit, also signals to PPARγ and may significantly affect adipogenesis and glucose sensitivity. Methods: To explore Gα_q’s role in adipocytes, we generated CRISPR-mediated Gα_q (Gnaq) knockout (Gnaq KO) and scramble control cells from 3T3-L1 preadipocytes. Results: The absence of Gα_q resulted in increased lipid accumulation and elevated serine 273 (but not serine 112) phosphorylation of PPARγ. Gα_q deficiency also decreased mitochondrial abundance and respiration in response to PPARγ ligands such as rosiglitazone, pioglitazone, and troglitazone. RNA sequencing comparing differentiated Gnaq KO and control adipocytes identified over 800 differentially expressed genes, including those associated with enhanced lipid metabolism and reduced inflammation. Corresponding PamGene kinome profiling showed increased serine/threonine kinase activity and decreased phosphotyrosine kinase signaling in Gnaq KO adipocytes. Conclusions: These findings support Gα_q as a regulator of adipocyte function, linking kinase signaling pathways to PPARγ-mediated transcription. This research provides mechanistic insights into targeting Gα_q as a potential treatment for individuals with obesity and metabolic disorders. Full article

Mitochondrial electron transport chain (ETC) dysfunction is a major driver of bioenergetic failure, redox imbalance, and drug toxicity, yet strategies to restore oxidative phosphorylation under ETC blockade remain limited. Redox-active small molecules could, in principle, shuttle electrons from NADH to distal ETC components and oxygen, thereby modulating both respiration and reactive oxygen species (ROS) formation. Here, we show that the enzyme-independent redox cycler phenazine methosulfate (PMS) rewires mitochondrial redox circuits and restores respiration in human glioblastoma cells and cell-free systems under ETC inhibition. At subtoxic concentrations, PMS acutely increased oxygen consumption and mitochondrial superoxide generation via NADH–PMS–O₂ redox cycling, while restoring mitochondrial membrane potential and ATP synthesis under ETC blockade, and shifting metabolism away from glycolytic lactate production. This profile is consistent with a protective redox-bypass role, distinct from the pro-apoptotic effects reported following high-dose, prolonged PMS exposure. The PMS-driven restoration of electron flow, mitochondrial membrane potential, and respiratory ATP synthesis under inhibition of Complex I (rotenone), III (antimycin A and myxothiazol), and/or IV (cyanide) is consistent with direct cytochrome c reduction, as demonstrated herein, and engagement of multiple ETC redox centers, including coenzyme Q₁₀. In metformin-treated cells, PMS reversed suppression of respiration and lactate accumulation, outperforming existing redox-bypass strategies. These findings identify PMS-driven redox cycling as a previously unrecognized chemical redox-bypass mechanism that both regenerates mitochondrial bioenergetics and reshapes ROS production, suggesting a potential approach to counteract drug- and toxin-induced mitochondrial dysfunction and to exploit redox vulnerabilities in cancer. Full article