Search Results (41,595)

Background/Objectives: In recent years, it has been suggested that sedatives may cause brain damage. One possible mechanism is interference with oxidative phosphorylation of brain mitochondria, but much remains unknown. In this study, we focused on dexmedetomidine, midazolam, and propofol, essential sedatives in anesthesia and intensive care, and aimed to understand the effects of these drugs on mouse brain mitochondria. Methods: We measured changes in mitochondrial respiratory capacity and swelling rate upon exposure to these sedatives in a wide concentration range. For the sedative that demonstrated impaired mitochondrial function we explored the possible involvement of mitochondrial permeability transition pore opening using brain mitochondria from cyclophilin D knockout (CypD KO) mice and detected cytochrome c (cyt c) release by Western blot. Results: Of the three sedatives, only high concentrations of propofol exhibited reduced respiratory capacity and mitochondrial swelling, toxicity which was not prevented by CypD KO. Furthermore, propofol did not induce cyt c release. Conclusions: These results suggest that propofol-induced brain mitochondrial dysfunction is a mechanism independent of mPTP opening. Full article

Cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy in which extracellular amyloid deposition leads to progressive structural and functional impairment. Beyond myocardial infiltration, growing evidence highlights the central role of autonomic nervous system dysfunction (ANS) —particularly the vagal nerve involvement—as a contributor to orthostatic intolerance, syncope, exercise limitation, arrhythmias, and reduced quality of life. Emerging data suggest that autonomic impairment may precede overt cardiac manifestations, offering a potential window for earlier recognition. This narrative review summarizes current knowledge on the mechanisms and clinical relevance of autonomic dysfunction in CA, emphasizing the novelty of the “vagal link” as a unifying framework connecting with a specific focus on the vagus nerve (VN) and its complex interplay with cardiac structure and function. We further discuss diagnostic approaches and the potential role of autonomic assessment in early detection, risk stratification, and personalized treatment strategies. A clearer understanding of vagal dysfunction may provide new insights into disease progression and identify opportunities for therapeutic innovation. Full article

Oxidation is a critical factor contributing to material wear and the degradation of conductive performance during current-carrying tribological processes. The present study investigated the composite oxidation mechanisms that occurred during current-carrying rolling in mixed atmospheres containing O₂ and H₂O vapor. The results obtained in a dry N₂/O₂ mixture, humid N₂, and humid N₂/O₂ mixture indicated that the oxidation mechanisms on current-carrying rolling surfaces involved thermal oxidation, tribo-oxidation, and anodic oxidation. XPS analysis confirmed that the primary oxidation product was CuO. Conductive atomic force microscopy (C-AFM) revealed that surface oxidation caused a significant reduction in conductive α-spots, leading to an increase in contact resistance. Contact resistance exhibited a quasi-linear relationship with the surface CuO content. Contact angle measurements and adhesion tests showed that the enhanced hydrophilicity of the oxidized surface and the resulting high adhesion contributed to an increase in the macroscopic friction coefficient. In humid N₂/O₂ with 50% relative humidity (RH), the friction coefficient rapidly exceeded 0.8 when the O₂ content surpassed 25%. Wear morphology analysis demonstrated that this abrupt increase in the friction coefficient induced fatigue wear on the surface. Overall, the present study elucidated the composite oxidation mechanisms during current-carrying rolling and clarified the pathways through which oxidation affected current-carrying tribological performance. These findings may contribute to improved failure analysis and the safe, reliable operation of electrical contact pairs. Full article

Myopathy encompasses a group of diseases characterized by abnormalities in both muscle function and structure. However, the underlying regulatory mechanisms of newly formed myofiber development remain poorly defined. No promising therapeutic approach has been developed, but numerous medication options are available to alleviate symptoms. Our previous studies demonstrated that adenosine kinase (ADK) is critical in regulating adenosine metabolism, pathological angiogenesis, pathological vascular remodeling, and vascular inflammatory diseases. Adenosine dynamically distributes between extracellular and intracellular, and adenosine concentration regulates ADK expression. However, the mechanism by which adenosine triggers an ADK-dependent intracellular signaling pathway to regulate skeletal muscle regeneration is not well defined. This study aimed to evaluate whether the adenosine-induced intracellular signaling pathway is involved in regulating myopathy, and how it regulates the development of newly formed myofibers. In this study, an intramuscular injection of cardiotoxin was used to induce a skeletal muscle injury model; satellite cells and C2C12 cells were employed. Whether adenosine regulates satellite cell activity, new myofiber formation and differentiation, as well as fusion of myofibers, were determined by H&E staining, BrdU incorporation assay, and spheroid sprouting assay. Interaction between ADK and PFKFB3 was evaluated by IF staining, PPI network analysis, molecular docking simulation, and CO-immunoprecipitation assay. The results demonstrated that adenosine dynamically distributes between extracellular and intracellular through concentrative nucleoside transports or equilibrative nucleoside transporters, and it rapidly induces an ADK-dependent intracellular signaling pathway, which interacts with PFKFB3-mediated glycolytic metabolism to promote satellite cell activity, new myofiber formation, differentiation, and fusion, and eventually enhances skeletal muscle regeneration after injury stress. The remarkable endogenous regeneration capacity of skeletal muscle, which is regulated by adenosine-triggered intracellular signaling, presents a promising therapeutic strategy for treating muscle trauma and muscular dystrophies. Full article

Salt-sensitive hypertension (SSH) is an important and common subtype of hypertension, whose pathogenesis involves multi-level regulation, including the central nervous system (CNS), metabolic stress, and epigenetics. Dietary bioactive compounds have emerged as a research hotspot for SSH intervention due to their safety and multi-target effects. Although existing studies have focused on the CNS regulation of SSH or the role of individual dietary components, there is a lack of comprehensive analysis integrating multiple mechanisms, systematically summarizing multiple compounds, and incorporating a clinical translation perspective. This review first outlines the mechanisms of CNS pathways, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and epigenetic modifications in SSH. Then, it systematically reviews the mechanisms of action and preclinical and clinical research progress of bioactive compounds, including capsaicin, taurine, gamma-aminobutyric acid, tea, and anthocyanins in SSH. In summary, this review systematically clarifies the complex regulatory network of SSH and the intervention potential of dietary bioactive compounds from an integrated perspective, innovatively proposes a precise dietary intervention framework, and fills the research gaps in the integration of multiple mechanisms and systematic evaluation of compounds in existing studies. This framework not only provides a new integrated perspective for the basic research of SSH but also offers key references for clinical dietary guidance, functional food development, and the formulation of targeted intervention strategies. Full article

Egg quality is a critical economic trait in poultry production, influencing consumer preference and production efficiency. The genetic and epigenetic regulation of egg quality involves complex biological pathways across various traits such as shell quality, albumen composition, and yolk biochemistry. This review synthesizes recent advances in the genetic, molecular, and epigenetic mechanisms that determine poultry egg quality. Specifically, it focuses on external traits such as eggshell strength, color, and thickness, and internal traits including albumen height, yolk composition, and the Haugh unit. Through genome-wide association studies (GWAS), quantitative trait loci (QTL) mapping, whole-genome sequencing (WGS), and multi-omics approaches, key candidate genes such as OC-116, CALB1, CA2 (shell formation), OVAL, SPINK5, SERPINB14 (albumen quality), and FGF9, PIAS1, NOX5 (lipid metabolism) have been identified. These genes play a pivotal role in shell biomineralization, albumen protein regulation, and yolk lipid transport. This review also explores the heritability of these traits, emphasizing the challenges posed by polygenic architecture and the influence of environmental factors. Furthermore, it addresses the dynamic spatiotemporal regulation of egg quality traits, including epigenetic layers such as DNA methylation, histone modifications, RNA methylation, and post-translational protein modifications. This paper highlights the application of these findings to breeding programs via genomic selection, marker-assisted breeding, and epigenetic engineering approaches. Future directions for precision breeding and the development of functional eggs with enhanced quality are also discussed. Full article

This study presents a comprehensive Raman spectroscopic and mechanical investigation of Gd₃Ga₅O₁₂ (GGG) single crystals irradiated with 231 MeV ¹³¹Xe ions at fluences ranging from 1 × 10¹¹ to 3.3 × 10¹³ ions/cm². Raman analysis reveals that all fundamental vibrational modes of the garnet structure remain observable up to the highest fluence, with the preservation of garnet crystalline topology/absence of secondary crystalline phases. However, significant line broadening (FWHM increase by 20–100%) and low-frequency shifts indicate progressive lattice disorder and phonon-defect scattering. High-frequency Ga-O stretching modes (A_1g, T_2g ~740 cm⁻¹) remain the most resistant to irradiation, while low-energy translational modes involving Gd³⁺ ions exhibit pronounced degradation and partial disappearance at high fluence. Complementary nanoindentation measurements show radiation-induced softening: hardness decreases by up to ≈60% at 3.3 × 10¹³ ions/cm², consistent with amorphization and overlapping ion tracks (~10–12 μm deep). Raman spectroscopy shows that the garnet lattice remains as the only crystalline phase up to 3.3 × 10¹³ ions/cm², while significant line broadening, mode suppression and a strong hardness decrease indicate progressive structural disorder and partial amorphization of the near-surface region. These results demonstrate that GGG maintains crystalline integrity below the track-overlap threshold (~6 keV/nm) but undergoes strong structural relaxation and mechanical weakening once this limit is exceeded. A new analytical methodology has been developed to quantify radiation-induced structural degradation. Full article

We present a novel concept of an electromagnetic mechanism for shifting the centre of gravity (CoG) in a small unmanned aerial vehicle with four rotors (quadrotor). Shifting the CoG is essential for controlling drones in which the thrust is unbalanced (e.g., upon the failure of one of the drives). The concept presented here involves using electromagnetic coils mounted under the drone and moving permanent magnets inside a cylindrical tube. Moving the positions of the masses can be controlled by means of currents in the coils. Changing the position of the magnets relative to the arms of the drone causes a shift in the CoG, allowing for controllability even when one of the four engines is not working, and making it possible for the drone to land safely. This article describes the geometrical and mechanical relationships in the proposed system, the design and numerical calculations of the electromagnetic mechanism with coils and permanent magnets, as well as the results of a simulation of the control variant. Additionally, the practical implementation of the mechanism, from CAD modelling through the manufacturing of its elements to the final structure prepared for mounting on a quadrotor, is discussed. Full article

The generation of synthetic cyber threat intelligence (CTI) has emerged as a significant area of research, particularly regarding the capacity of large language models (LLMs) to produce realistic yet deceptive security content. This study explores both the generative and evaluative aspects of CTI synthesis by employing a custom-developed detection system and publicly accessible LLMs. The evaluation combined automated analysis with a human study involving cybersecurity professionals. The results indicate that even a compact, resource-efficient fine-tuned model can generate highly convincing CTI misinformation capable of deceiving experts and AI-based classifiers. Human participants achieved an average accuracy around 50% in distinguishing between authentic and generated CTI reports. However, the proposed hybrid detection model achieved 98.5% accuracy on the test set and maintained strong generalization with 88.5% accuracy on unseen data. These findings demonstrate both the potential of lightweight models to generate credible CTI narratives and the effectiveness of specialized detection systems in mitigating such threats. The study underscores the growing risk of harmful misinformation in AI-driven CTI and highlights the importance of incorporating robust validation mechanisms within cybersecurity infrastructures to enhance defense resilience. Full article

Most land plants engage in a mutualistic interaction with arbuscular mycorrhizal fungi (AMF), for which Rhizophagus irregularis is a model species. Like plant pathogenic fungi, AMF genomes encode hundreds of putative effector proteins. However, for only a few, the molecular mechanisms by which they alter the host’s physiology are known. Here, we combined several reverse genetic approaches to unravel the role of the RIRG190 effector protein in arbuscular mycorrhiza (AM) symbiosis. Using multiple heterologous tools, evidence is provided that the RIRG190 effector is secreted and localizes to the plant nucleus. Moreover, by means of yeast two-hybrid (Y2H) and ratiometric bimolecular fluorescence complementation (rBIFC) assays, the data demonstrate that RIRG190 interacts with the protein Something About Silencing (SAS10), known to be involved in rRNA biogenesis in the nucleolus of cortical cells. Our findings suggest that rRNA biogenesis is a key process modulated by AMF, potentially to enhance plant metabolic activity, facilitating cell cycle progression, and to support the establishment of the symbiosis. Full article

Background/Objectives: Conversations about end-of-life care or advance care planning are often difficult and emotionally challenging to initiate. Tailoring messages to the specific audiences can make these sensitive discussions more manageable and effective. The Evidence-based Model for the Transfer and Exchange of Research Knowledge (EMTReK), compromising six core components (message, stakeholders, processes, context, facilitation, and evaluation) offers a structured framework for research dissemination and knowledge transfer in palliative and long-term care settings. Knowledge translation bridges research and practice, with its effectiveness depending on stakeholder engagement, tailored communication, and systematic application of evidence in policy and practice. This study explores stakeholder perspectives on a dementia care intervention, using EMTReK as an analytical framework to examine how knowledge transfer and exchange (KTE) actions were implemented across long-term care settings. Methods: A qualitative analysis was conducted on primary data comprising case narratives from multinational research groups involved in the “Caregiver Decision Support” (mySupport) study (2019–2023). Teams from Canada, the Czech Republic, Ireland, Italy, the Netherlands, and the United Kingdom evaluated the mySupport intervention through interviews, with analysis guided by components of the EMTReK model. Results: Facilitated Family Care Conferences were found to be effective mechanisms for supporting knowledge transfer and intervention uptake in dementia care across nursing homes in Europe and Canada. Despite challenges posed by the COVID-19 pandemic, Family Care Conferences adapted through stakeholder engagement, interactive learning, and innovative communication methods. Using EMTReK as an analytical framework, the research team identified key elements that contributed to successful implementation, including the importance of flexibility to accommodate local contexts. Conclusions: The transnational application of the EMTReK model for advance care planning in long-term dementia care highlights the importance of tailored, culturally relevant knowledge translation strategies, which, despite challenges from the COVID-19 pandemic, were successfully implemented through local adaptations and diverse dissemination methods, emphasising the need for further research on their impact on resident and family outcomes. Full article

Carbon fiber reinforced silicon carbide (C/SiC) composite material exhibits exceptional properties, including high strength, high stiffness, low density, outstanding high-temperature performance, and corrosion resistance. Consequently, they are widely used in aerospace, defense, and automotive engineering. However, their anisotropic, high hardness, and brittle characteristics make them a typical difficult-to-machine material. This paper focuses on achieving high-quality micro hole machining of C/SiC composite material via electrical discharge machining. It systematically investigates electrical discharge machining characteristics and innovatively develops a hollow internal flow helical electrode reaming process. Experimental results reveal four typical chip morphologies: spherical, columnar, blocky, and molten. The study uncovers a multi-mechanism cutting process: the EDM ablation of the composite involves material melting and explosive vaporization, the intact extraction and fracture of carbon fibers, and the brittle fracture and spalling of the SiC matrix. Discharge energy correlates closely with surface roughness: higher energy removes more SiC, resulting in greater roughness, while lower energy concentrates on m fibers, yielding higher vaporization rates. C fiber orientation significantly impacts removal rates: processing time is shortest at θ = 90°, longest at θ = 0°, and increases as θ decreases. Typical defects such as delamination were observed between alternating 0° and 90° fiber bundles or at hole entrances. Cracks were also detected at the SiC matrix–C fiber interface. The proposed hole-enlargement process enhances chip removal efficiency through its helical structure and internal flushing, reduces abnormal discharges, mitigates micro hole taper, and thereby improves forming quality. This study provides practical references for the EDM of C/SiC composite material. Full article

Driven by the surging global demand for crude oil and its byproducts, liquid tanker vessels have undergone a marked shift toward ultra-large dimensions. This growth, while enhancing transport capacity, has also intensified congestion across many liquid terminals. As the Dead Weight Tonnage (DWT) of vessels rises, so does their draft, often requiring tide-dependent navigation for safe entry into ports. To address the resulting operational complexities, this study investigates the coordinated scheduling of three critical resources—channels, tugboats, and berths—at liquid terminals. A novel optimization framework, termed the Channel-Tugboat-Berth-Tide (CUBT) model, is proposed. The primary objective is to minimize the total operational cost over a planning horizon, accounting for anchorage waiting time, channel occupancy, tugboat utilization, and penalties from delayed departures. To solve this model efficiently, we adopt an enhanced variant of the Logistic-Hybrid-Adaptive Black Widow Optimization Algorithm (LHA-BWOA), incorporating Logistic-Sine-Cosine Chaotic Map (LSC-CM) initialization, hybrid reproduction mechanisms, and dynamic parameter adaptation. A series of case studies involving varying planning cycles are conducted to validate the model’s practical viability. Furthermore, sensitivity analyses are performed to evaluate the impact of channel choice, tugboat allocation, and vessel waiting time. Results indicate that tugboat operations account for the largest portion of the total costs. Notably, while two-way channels result in lower direct channel costs, they do not always yield the lowest overall expenditure. Among the service strategies evaluated, the First-In–First-Out (FIFO) rule is found to be the most cost-efficient. The results offer practical guidance for port improving the operational efficiency of liquid terminals under complex tidal and resource constraints. Full article

Freeform surfaces play a critical role in complex light-field modulation. However, traditional geometric mapping and standard optimization methods are limited by computational cost and convergence instability in large-scale ray tracing and complex surface modeling. This paper introduces DiffRayFlow, which integrates discrete optimal transport (OT), end-to-end differentiable ray tracing (DRT), and an adaptive multi-scale strategy. OT provides a global, energy-conserving geometric map. Differentiable tracing parameterizes the surface using the finite difference method (FDM) and constructs a differentiable link from height parameters to target landing points. The multi-scale approach, combined with early stopping, enhances efficiency and stability. For typical tasks involving over a million rays, the core heightmap optimization is usually completed within 20 s. The method can output standard Computer-Aided Design (CAD) data for rapid prototyping and physical validation. Ablation studies show that the multi-scale strategy is key to achieving high-precision convergence, while the early stopping mechanism can reduce optimization time by about 40% without sacrificing reconstruction quality. DiffRayFlow provides an efficient engineering path for interactive design and large-scale customization. Full article

Background: Chronic inflammation is a hallmark of many oral and systemic diseases and has long been recognised as a risk factor for cancer development. Central to inflammatory responses are inflammasomes—multiprotein complexes that, upon activation, trigger caspase-1–mediated release of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Their emerging contribution to chronic oral inflammatory conditions has generated interest in understanding whether persistent inflammasome activity may also influence pathways involved in oral carcinogenesis. This review summarises current evidence on the role of inflammasomes in oral inflammatory diseases and explores their potential involvement in the transition from chronic inflammation to malignant transformation. Methods: A narrative review of the literature was conducted by searching major scientific databases for studies investigating inflammasome activation in oral tissues, inflammatory oral diseases, and mechanisms linking chronic inflammation to oral cancer. Eligible articles included experimental studies, animal models, observational clinical research, and review papers that provided mechanistic or associative insights. Due to heterogeneity in study designs, a qualitative synthesis was performed. Results: Available evidence indicates that inflammasomes, particularly NLRP3 and AIM2, contribute to the pathophysiology of pulpitis, periodontitis, and several systemic conditions that affect oral health. Preclinical and observational findings also suggest potential involvement of inflammasome-related pathways in early tumorigenic processes, although these associations require further clarification. Preliminary biomarker-based studies demonstrate that inflammasome components measurable in saliva, pulpal blood, or gingival crevicular fluid may offer minimally invasive indicators of inflammatory burden and oral health status. Conclusions: Inflammasomes appear to play a meaningful role in oral inflammatory diseases, and growing evidence links their persistent activation to mechanisms relevant to oral carcinogenesis. However, current findings are largely associative and derived primarily from experimental and early clinical research. Additional work is needed to define precisely how inflammasomes contribute to the progression from chronic oral inflammation toward malignant change and to evaluate whether targeting inflammasome pathways offers viable therapeutic or diagnostic potential. Full article