Search Results (309)

Status epilepticus occurs when a seizure lasts more than five minutes or when multiple seizures occur with incomplete return to baseline. SE induces a myriad of pathological changes involving synaptic and extra-synaptic factors. The transition from a self-limiting seizure to a self-sustaining one is established by maladaptive receptor trafficking, whereby GABA_A receptors are progressively endocytosed while glutamatergic receptors (NMDA and AMPA) are transported to the synaptic membrane, causing excitotoxicity and alteration in glutamate-dependent downstream signaling. The subsequent influx of Ca²⁺ exposes neurons to increased levels of [Ca²⁺]i, which overwhelms mitochondrial buffering, resulting in irreversible mitochondrial membrane depolarization and mitochondrial injury. Oxidative stress resulting from mitochondrial leakage and increased production of reactive oxygen species activates the inflammasome and induces a damage-associated molecular pattern. Neuroinflammation perpetuates oxidative stress and exacerbates mitochondrial injury, thereby jeopardizing mitochondrial energy supply in a state of accelerated ATP consumption. Additionally, Ca²⁺ overload can directly damage neurons by activating enzymes involved in the breakdown of proteins, phospholipids, and nucleic acids. The cumulative effect of these effector pathways is neuronal injury and neuronal death. Surviving neurons undergo long-term alterations that serve as a substrate for epileptogenesis. This review highlights the multifaceted mechanisms underlying SE self-sustainability, pharmacoresistance, and subsequent epileptogenesis. Full article

β-hydroxybutyrate (BHB) is the most abundant ketone body produced during ketosis, a process initiated by glucose depletion and the β-oxidation of fatty acids in hepatocytes. Traditionally recognized as an alternative energy substrate during fasting, caloric restriction, and starvation, BHB has gained attention for its diverse signaling roles in various physiological processes. This review explores the emerging therapeutic potential of BHB in the context of sarcopenia, metabolic disorders, and neurodegenerative diseases. BHB influences gene expression, lipid metabolism, and inflammation through its inhibition of Class I Histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs), specifically HCAR2 and FFAR3. These actions lead to enhanced mitochondrial function, reduced oxidative stress, and regulation of inflammatory pathways, with implication for muscle maintenance, neuroprotection, and metabolic regulation. Moreover, BHB’s ability to modulate adipose tissue lipolysis and immune responses highlight its broader potential in managing chronic metabolic conditions and aging. While these findings show BHB as a promising therapeutic agent, further research is required to determine optimal dosing strategies, long-term effects, and its translational potential in clinical settings. Understanding BHB’s mechanisms will facilitate its development as a novel therapeutic strategy for multiple organ systems affected by aging and disease. Full article

The ratchet click mechanism in mechanical watch movements is a micro-component essential to prevent the unwinding of the caliber mainspring, providing secure energy storage during recharging. Despite its geometrical simplicity, the ratchet click undergoes to a complex distribution of stress, elevated strains, and cyclical mechanical deformations, affecting its long-term reliability. Despite being a crucial element in all mechanical watch movements, the non-return system appears to have been overlooked in scientific literature, with no studies available on its design, modeling, and micromachining. In this work, we introduce a novel Finite Element Method (FEM) -based design strategy for the ratchet click, systematically refining its geometry and dimensional parameters to minimize peak stress and improve durability. A mechanical simulation model was created to simulate the boundary conditions, contact interactions, and stress distributions on the part. If compared with the standard component, the optimized design exhibits a decrease in peak stress values. The mechanism was micro-machined, and it was experimentally tested to validate the numerical model outputs. The integrated digital–physical approach not only underscores the scientific contribution of coupling advanced simulation with experimental validation of complex micromechanisms but also provides a generalizable method for enhancing performance of micro-mechanical components while preserving their historical design heritage. Full article

With their superior switching speed, GaN high-electron-mobility transistors (HEMTs) enable high power density, reduce energy losses, and increase power efficiency in a wide range of applications, such as power electronics, due to their high breakdown voltage. GaN-HEMT devices are subject to long-term reliability due to the self-heating effect and lattice mismatch between the SiC substrate and the GaN. Depletion-mode GaN HEMTs are utilized for radio frequency applications, and this work investigates three wide-bandgap (WBG) GaN HEMT fixed-frequency oscillators with output buffers. The first GaN-on-SiC HEMT oscillator consists of an HEMT amplifier with an LC feedback network. With the supply voltage of 0.8 V, the single-ended GaN oscillator can generate a signal at 8.85 GHz, and it also supplies output power of 2.4 dBm with a buffer supply of 3.0 V. At 1 MHz frequency offset from the carrier, the phase noise is −124.8 dBc/Hz, and the figure of merit (FOM) of the oscillator is −199.8 dBc/Hz. After the previous study, the hot-carrier stressed RF performance of the GaN oscillator is studied, and the oscillator was subject to a drain supply of 8 V for a stressing step time equal to 30 min and measured at the supply voltage of 0.8 V after the step operation for performance benchmark. Stress study indicates the power oscillator with buffer is a good structure for a reliable structure by operating the oscillator core at low supply and the buffer at high supply. The second balanced oscillator can generate a differential signal. The feedback filter consists of a left-handed transmission-line LC network by cascading three unit cells. At a 1 MHz frequency offset from the carrier of 3.818 GHz, the phase noise is −131.73 dBc/Hz, and the FOM of the 2nd oscillator is −188.4 dBc/Hz. High supply voltage operation shows phase noise degradation. The third GaN cross-coupled VCO uses 8-shaped inductors. The VCO uses a pair of drain inductors to improve the Q-factor of the LC tank, and it uses 8-shaped inductors for magnetic coupling noise suppression. At the VCO-core supply of 1.3 V and high buffer supply, the FOM at 6.397 GHz is −190.09 dBc/Hz. This work enhances the design techniques for reliable GaN HEMT oscillators and knowledge to design high-performance circuits. Full article

Tribological processes in extreme environments pose serious material challenges, requiring coatings that resist both wear and corrosion. This review summarizes recent advances in protective coatings engineered for extreme environments such as high temperatures, chemically aggressive media, and high-pressure and abrasive domains, as well as cryogenic and space applications. A comprehensive overview of promising coating materials is provided, including ceramic-based coatings, metallic and alloy coatings, and polymer and composite systems, as well as nanostructured and multilayered architectures. These materials are deployed using advanced coating technologies such as thermal spraying (plasma spray, high-velocity oxygen fuel (HVOF), and cold spray), chemical and physical vapor deposition (CVD and PVD), electrochemical methods (electrodeposition), additive manufacturing, and in situ coating approaches. Key degradation mechanisms such as adhesive and abrasive wear, oxidation, hot corrosion, stress corrosion cracking, and tribocorrosion are examined with coating performance. The review also explores application-specific needs in aerospace, marine, energy, biomedical, and mining sectors operating in aggressive physiological environments. Emerging trends in the field are highlighted, including self-healing and smart coatings, environmentally friendly coating technologies, functionally graded and nanostructured coatings, and the integration of machine learning in coating design and optimization. Finally, the review addresses broader considerations such as scalability, cost-effectiveness, long-term durability, maintenance requirements, and environmental regulations. This comprehensive analysis aims to synthesize current knowledge while identifying future directions for innovation in protective coatings for extreme environments. Full article

In this research, a single composite-type stretchable triboelectric nanogenerator (TENG) is proposed for efficient energy harvesting and handwriting recognition. The composite TENGs were fabricated by blending dielectric barium titanate (BT) and conductive carbon nanotubes (CNTs) in varying amounts into a styrene–butadiene rubber matrix. The energy harvesting efficiency depends on the type and amount of fillers, as well as their dispersion within the matrix. Stearic acid modification of BT enables near-nanoscale filler distribution, resulting in high energy conversion efficiencies. The composite achieved power efficiency, power density, charge efficiency, and charge density values of 1.127 nW/N, 8.258 mW/m³, 0.146 nC/N, and 1.072 mC/m³, respectively, under only 2% cyclic compressive strain at 0.85 Hz. The material performs better at low stress–strain ranges, exhibiting higher charge efficiency. The generated charge in the TENG composite is well correlated with the compressive stress, which provides a minimum activation pressure of 0.144 kPa, making it suitable for low-pressure sensing applications. A flat composite with dimensions of 0.02 × 6 × 5 cm³ can produce a power density of 26.04 W/m³, a charge density of 0.205 mC/m³, and an output voltage of 10 V from a single hand pat. The rubber composite also demonstrates high accuracy in handwriting recognition across different individuals, with clear differences in sensitivity curves. Repeated attempts by the same person show minimal deviation (<5%) in writing time. Additionally, the presence of reinforcing fillers enhances mechanical strength and durability, making the composite suitable for long-term cyclic energy harvesting and wearable sensor applications. Full article

The fatigue resistance of cement-stabilized macadam (CSM) plays a vital role in ensuring the long-term durability of pavement structures. However, limited cementitious material (CM) content often leads to high packing voids, which significantly compromise fatigue performance. Existing studies have rarely explored the coupled mechanism between pore structure and fatigue behavior, especially in the context of solid-waste-based CMs. In this study, a cost-effective alkali-activated sludge gasification slag (ASS) was proposed as a sustainable CM substitute for ordinary Portland cement (OPC) in CSM. A dual evaluation approach combining cross-sectional image analysis and fatigue loading tests was employed to reveal the effect pathway of void structure optimization on fatigue resistance. The results showed that ASS exhibited excellent cementitious reactivity, forming highly polymerized C-A-S-H/C-S-H gels that contributed to a denser microstructure and superior mechanical performance. At a 6% binder dosage, the void ratio of ASS–CSM was reduced to 30%, 3% lower than that of OPC–CSM. The 28-day unconfined compressive strength and compressive resilient modulus reached 5.7 MPa and 1183 MPa, representing improvements of 35.7% and 4.1% compared to those of OPC. Under cyclic loading, the ASS system achieved higher energy absorption and more uniform stress distribution, effectively suppressing fatigue crack initiation and propagation. Moreover, the production cost and carbon emissions of ASS were 249.52 CNY/t and 174.51 kg CO₂e/t—reductions of 10.9% and 76.2% relative to those of OPC, respectively. These findings demonstrate that ASS not only improves fatigue performance through pore structure refinement but also offers significant economic and environmental advantages, providing a theoretical foundation for the large-scale application of solid-waste-based binders in pavement engineering. Full article

Despite the known impacts of weaning on animal health, the underlying molecular mechanisms remain unclear, particularly how psychological and nutritional stress differentially affect gut health and immune function over time. This study hypothesized that early weaning exerts distinct short- and long-term effects on lamb stress physiology, immunity, and gut health, mediated by specific molecular pathways. Twelve pairs of full-sibling male Hu sheep lambs were assigned to control (CON) or early-weaned (EW) groups. Plasma stress/immune markers were dynamically monitored, and intestinal morphology, antioxidant capacity, apoptosis, and transcriptomic profiles were analyzed at 5 and 28 days post-weaning. Early weaning triggered transient psychological stress, elevating hypothalamic–pituitary–adrenal (HPA) axis hormones (cortisol, catecholamines) and inflammatory cytokines (TNF-α) within 1 day (p < 0.05); however, stress responses were transient and recovered by 7 days post-weaning. Sustained intestinal remodeling was observed in EW lambs, featuring reduced ileal villus height, increased crypt depth (p < 0.05), and oxidative damage (MDA levels doubled vs. CON; p < 0.01). Compensatory epithelial adaptation included increased crypt depth but paradoxically reduced villus tip apoptosis. The transcriptome analysis revealed significant changes in gene expression related to immune function, fat digestion, and metabolism. Key DEGs included APOA4, linked to lipid transport adaptation; NOS2, associated with nitric oxide-mediated immune–metabolic crosstalk; and mitochondrial gene COX1, reflecting energy metabolism dysregulation. Protein–protein interaction analysis revealed NOS2 as a hub gene interacting with IDO1 and CXCL11, connecting oxidative stress to immune cell recruitment. Early weaning exerts minimal lasting psychological stress but drives persistent gut dysfunction through transcriptome-mediated changes in metabolic and immune pathways, highlighting key genes such as APOA4, NOS2, and COX1 as potential regulators of these effects. Full article

Underground hydrogen storage (UHS) in geological formations offers a promising solution for large-scale energy buffering, but its long-term safety and mechanical stability remain concerns, particularly in fractured rock environments. This study develops a fully coupled thermo-mechanical model to investigate the cyclic response of a dual-cavern hydrogen storage system with polymer-based sealing layers. The model incorporates non-isothermal gas behavior, rock heterogeneity via a Weibull distribution, and fracture networks represented through stochastic geometry. Two operational scenarios, single-cavern and dual-cavern cycling, are simulated to evaluate stress evolution, displacement, and inter-cavity interaction under repeated pressurization. Results reveal that simultaneous operation of adjacent caverns amplifies tensile and compressive stress concentrations, especially in inter-cavity rock bridges (i.e., the intact rock zones separating adjacent caverns) and fracture-dense zones. Polymer sealing layers remain under compressive stress but exhibit increased residual deformation under cyclic loading. Contour analyses further show that fracture orientation and spatial distribution significantly influence stress redistribution and deformation localization. The findings highlight the importance of considering thermo-mechanical coupling and rock fracture mechanics in the design and operation of multicavity UHS systems. This modeling framework provides a robust tool for evaluating storage performance and informing safe deployment in complex geological environments. Full article

A high-fat diet (HFD) has significant effects on health, leading to cardiovascular, metabolic, neurodegenerative, and psychiatric conditions and contributing to obesity and type 2 diabetes. Mitochondria, essential for energy production and oxidative metabolism, are adversely affected by a HFD, causing oxidative stress and impaired cellular function. Mutations in the OPA1 (OPtic Atrophy 1) gene, crucial for mitochondrial dynamics and functions, are responsible for dominant optic atrophy (DOA), a mitochondrial neurodegenerative disease associated with increased reactive oxygen species (ROS). The expressivity of DOA is highly variable, even within the same family. This suggests that both modifying genetics and environmental factors could influence the penetrance of the disease. We previously demonstrated that genetic background modulates DOA expressivity and now ask if this is also the case for external cues. We thus explore how OPA1 deficiency interacts with HFD-induced metabolic disturbances, hypothesizing that long-term HFD consumption impairs brain mitochondrial function and disrupts oxidative metabolism. OPA1^+/− mice were thus subjected to a HFD for a period of 12 weeks, and ROS levels and the expression of antioxidant genes were evaluated by Western blot and spectrophotometry. Cortices from high-fat diet-fed OPA1^+/− mice showed lower aconitase activity than those of their wild-type (WT) litter mates, indicative of an unbalanced increase in mitochondrial ROS. Accordingly, OPA1^+/− mice present lower levels of the antioxidant enzyme superoxide dismutase 2 compared to WT mice. Therefore, this study (i) reveals the onset of oxidative stress in brain cortices from OPA1^+/− mice challenged with a HFD, (ii) shows that diet is a modifying factor for DOA, and (iii) suggests that food control could be used to moderate the severity of the disease. Full article

Respiratory infections caused by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus pose significant global health challenges, leading to high morbidity and mortality, particularly in vulnerable populations. Despite their distinct virological characteristics, these viruses exploit host cellular metabolism to support replication, modulate immune responses, and promote disease progression. Emerging evidence shows that they induce metabolic reprogramming, shifting cellular energy production toward glycolysis to meet the bioenergetic demands of viral replication. Additionally, alterations in lipid metabolism, including enhanced fatty acid synthesis and disrupted cholesterol homeostasis, facilitate viral entry, replication, and immune evasion. The dysregulation of mitochondrial function and oxidative stress pathways also contributes to disease severity and long-term complications, such as persistent inflammation and immune exhaustion. Understanding these metabolic shifts is crucial for identifying new therapeutic targets and novel biomarkers for early disease detection, prognosis, and patient stratification. This review provides an overview of the metabolic alterations induced by severe acute respiratory syndrome coronavirus 2, influenza virus, and respiratory syncytial virus, highlighting shared and virus-specific mechanisms and potential therapeutic interventions. Full article

The Beijing–Tianjin–Hebei (BTH) region is one of China’s most water-scarce yet economically vital areas, facing increasing challenges due to climate change and intensive human activities. This study develops an integrated Water–Food–Energy–Ecology (WFEE) simulation and regulation model to assess the system’s stability under coordinated development scenarios and extreme climate stress. A 500-year precipitation series was reconstructed using historical drought and flood records combined with wavelet analysis and machine learning models (Random Forest and Support Vector Regression). Results show that during the reconstructed historical megadrought (1633–1647), with average precipitation anomalies reaching −20% to −27%, leading to a regional water shortage rate of 16.9%, food self-sufficiency as low as 44.7%, and a critical reduction in ecological river discharge. Under future recommended scenario with enhanced water conservation, reclaimed water reuse, and expanded inter-basin transfers, the region could maintain a water shortage rate of 2.6%, achieve 69.3% food self-sufficiency, and support ecological water demand. However, long-term water resource degradation could still reduce food self-sufficiency to 62.9% and ecological outflows by 20%. The findings provide insights into adaptive water management, highlight the vulnerability of highly coupled systems to prolonged droughts, and support regional policy decisions on resilience-oriented water infrastructure planning. Full article

Acute heart failure (AHF) is a clinical syndrome characterized by the sudden onset or rapid worsening of heart failure signs and symptoms, frequently triggered by myocardial ischemia, pressure overload, or cardiotoxic injury. A central component of its pathophysiology is the activation of intracellular signal transduction cascades that translate extracellular stress into cellular responses. Among these, the mitogen-activated protein kinase (MAPK) pathways have received considerable attention due to their roles in mediating inflammation, apoptosis, hypertrophy, and adverse cardiac remodeling. The canonical MAPK cascades—including extracellular signal-regulated kinases (ERK1/2), p38 MAPK, and c-Jun N-terminal kinases (JNK)—are activated by upstream stimuli such as angiotensin II (Ang II), aldosterone, endothelin-1 (ET-1), and sustained catecholamine release. Additionally, emerging evidence highlights the role of receptor-mediated signaling, cellular stress, and myeloid cell-driven coagulation events in linking MAPK activation to fibrotic remodeling following myocardial infarction. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade plays a central role in regulating cardiomyocyte survival, hypertrophy, energy metabolism, and inflammation. Activation of the PI3K/Akt pathway has been shown to confer cardioprotective effects by enhancing anti-apoptotic and pro-survival signaling; however, aberrant or sustained activation may contribute to maladaptive remodeling and progressive cardiac dysfunction. In the context of AHF, understanding the dual role of this pathway is crucial, as it functions both as a marker of compensatory adaptation and as a potential therapeutic target. Recent reviews and preclinical studies have linked PI3K/Akt activation with reduced myocardial apoptosis and attenuation of pro-inflammatory cascades that exacerbate heart failure. Among the multiple signaling pathways involved, glycogen synthase kinase-3β (GSK-3β) has emerged as a key regulator of apoptosis, inflammation, metabolic homeostasis, and cardiac remodeling. Recent studies underscore its dual function as both a negative regulator of pathological hypertrophy and a modulator of cell survival, making it a compelling therapeutic candidate in acute cardiac settings. While earlier investigations focused primarily on chronic heart failure and long-term remodeling, growing evidence now supports a critical role for GSK-3β dysregulation in acute myocardial stress and injury. This comprehensive review discusses recent advances in our understanding of the MAPK signaling pathway, the PI3K/Akt cascade, and GSK-3β activity in AHF, with a particular emphasis on mechanistic insights, preclinical models, and emerging therapeutic targets. Full article

This article reviews the multifaceted roles of itaconate in immune regulation and inflammatory metabolism. Itaconic acid is a dicarboxylic acid with anti-inflammatory, antioxidant, and anti-tumor properties. It is initially produced by the heating decomposition of citric acid and is closely related to the tricarboxylic acid cycle. In immune regulation, itaconate regulates macrophage function through a variety of mechanisms, including metabolic reprogramming, polarization regulation, inhibition of cytokine production, and regulation of oxidative stress. It can also affect the function of T cells and B cells. In terms of inflammatory metabolism, itaconate can regulate the production of inflammatory factors, inhibit the activity of succinate dehydrogenase, and affect cellular energy metabolism and lipid metabolism. Its mechanism of action involves the inhibition of succinate dehydrogenase, covalent modification of proteins, influence on epigenetic modification, and playing a role through the G protein-coupled receptor OXGR1 (Oxoglutarate Receptor 1). Itaconic acid derivatives have shown good effects in anti-inflammation and anti-oxidation and have broad application prospects in clinical treatment, including the treatment of inflammatory diseases, anti-tumor and anti-microbial infection. However, the long-term safety and side effects of itaconic acid as a therapeutic agent still need to be further studied. Future studies will further explore the synthesis and function of itaconic acid in different cell types, its physiological effects in non-inflammatory conditions, and its potential application in clinical treatment in order to develop new therapeutic strategies and improve the treatment effect of chronic inflammatory and metabolism-related diseases. Full article

Magnetorheological (MR) foams represent a class of smart materials with unique tunable viscoelastic properties when subjected to external magnetic fields. Combining porous structures with embedded magnetic particles, these materials address challenges such as leakage and sedimentation, typically encountered in conventional MR fluids while offering advantages like lightweight design, acoustic absorption, high energy harvesting capability, and tailored mechanical responses. Despite their potential, challenges such as non-uniform particle dispersion, limited durability under cyclic loads, and suboptimal magneto-mechanical coupling continue to hinder their broader adoption. This review systematically addresses these issues by evaluating the synthesis methods (ex situ vs. in situ), microstructural design strategies, and the role of magnetic particle alignment under varying curing conditions. Special attention is given to the influence of material composition—including matrix types, magnetic fillers, and additives—on the mechanical and magnetorheological behaviors. While the primary focus of this review is on MR foams, relevant studies on MR elastomers, which share fundamental principles, are also considered to provide a broader context. Recent advancements are also discussed, including the growing use of artificial intelligence (AI) to predict the rheological and magneto-mechanical behavior of MR materials, model complex device responses, and optimize material composition and processing conditions. AI applications in MR systems range from estimating shear stress, viscosity, and storage/loss moduli to analyzing nonlinear hysteresis, magnetostriction, and mixed-mode loading behavior. These data-driven approaches offer powerful new capabilities for material design and performance optimization, helping overcome long-standing limitations in conventional modeling techniques. Despite significant progress in MR foams, several challenges remain to be addressed, including achieving uniform particle dispersion, enhancing viscoelastic performance (storage modulus and MR effect), and improving durability under cyclic loading. Addressing these issues is essential for unlocking the full potential of MR foams in demanding applications where consistent performance, mechanical reliability, and long-term stability are crucial for safety, effectiveness, and operational longevity. By bridging experimental methods, theoretical modeling, and AI-driven design, this work identifies pathways toward enhancing the functionality and reliability of MR foams for applications in vibration damping, energy harvesting, biomedical devices, and soft robotics. Full article