Search Results (15,639)

Epilepsy affects more than 50 million individuals worldwide, and approximately one-third of patients remain refractory to existing antiseizure medications. Advances in gene therapy and genome editing have opened new possibilities for disease-modifying interventions that directly target the molecular and circuit-level mechanisms underlying epileptogenesis. Recent progress in central nervous system tropic viral vectors, non-viral delivery systems, and programmable genome-editing technologies has enabled precise manipulation of neuronal and glial function in preclinical epilepsy models. Strategies range from restoration of haploinsufficient genes implicated in monogenic epilepsies, such as SCN1A in Dravet syndrome, to modulation of neuronal excitability through engineered ion channels, neuropeptides, and astrocyte-based approaches. In parallel, CRISPR-derived platforms, including transcriptional activation and repression systems, base editing, and prime editing, offer new avenues for regulating gene expression in post-mitotic neurons without introducing double-strand DNA breaks. Despite these advances, significant translational challenges remain, including efficient and cell-type-specific delivery, long-term safety, and the risk of network-level side effects in the epileptic brain. This review critically examines recent gene therapy and genome-editing approaches for epilepsy, highlights key technological and biological barriers to clinical translation, and discusses emerging strategies that may enable durable and targeted treatments for drug-resistant epilepsies. Full article

In this study, hardfacing and a flux-cored/self-shielded powder wire of the FCAW-S-90G13N4 type was employed to produce and investigate the deposits of high-manganese steel. The effects of high-frequency mechanical impact (HFMI) treatment on the microstructure, hardening, and scratch resistance of the deposits were studied to evaluate and predict the impact wear resistance of the hardfacing deposits under controlled impact load conditions. As observed by XRD, SEM, and nanoindentation, the microstructure of deposited metal comprised a soft austenite matrix, dispersed hard carbides, and an ε phase (~26 vol.%). The wear resistance is thus not controlled by carbides alone but arises from the synergistic action of a hard carbide network within a ductile matrix. HFMI resulted in twinning, an increase in dislocation density, a grown volume fraction of ε (>60%) and α′-martensite. The interaction between twins, martensites, and dislocations provides a double/triple increase in microhardness (from HV_0.2 = 2.78 GPa to HV_0.2 = 6–7.69 GPa). After HFMI, scratch tests showed lower restored depths of scratch tracks and a 36–68% deceleration in the wear rate regarding those of the initial deposit. The underlying wear mechanisms were assessed accounting for the SEM observations of the scratch track morphologies and a ‘counterbody penetration vs. shear stresses ratio’ map. The initial plastic deformation-related mechanism (wedge/pile-up formation) changed by HFMI to ploughing. The obtained results allow one to evaluate and predict the impact wear resistance of the hardfacing deposits under controlled impact load conditions. Full article

Grey plastic is a representative traditional architectural decoration craft in the Lingnan region in China, carrying rich historical and cultural values as well as distinctive regional artistic characteristics. However, the grey plastic craft is currently facing problems such as inheritance gaps and a shortage of craftsmen, and its restoration projects impose extremely high professional requirements on contractors. Existing contractor selection methods are mostly applicable to ordinary construction projects and are difficult to adapt to its particularity, which may easily lead to risks such as substandard restoration quality. Therefore, this paper proposes a contractor selection method for grey plastic decoration projects of cultural relic buildings based on the BWM-TODIM method. Firstly, an evaluation system covering six core criteria is constructed; secondly, the BWM is adopted to determine the criteria weights; thirdly, the TODIM method is used to characterize the decision-makers’ loss aversion psychology and rank the candidate contractors; finally, an empirical analysis is conducted with a grey plastic restoration project in Lingnan as a case to verify the feasibility and effectiveness of the method. This study can provide decision support for the scientific selection of contractors for grey plastic decoration projects and contribute to the sustainable protection of cultural heritage. The scope of this study is limited to contractor selection for grey plaster decoration engineering of cultural relic buildings. Full article

Background/Objectives: The aim of the current study was to investigate the mechanistic hepatoprotective efficacy of selenium (SE) and chitosan-coated selenium nanoparticles (CS-SENPs) using a rat model induced by lipopolysaccharide (LPS). Methods: CS-SENP was prepared and characterized for particle size, polydispersity index (PDI), zeta potential, transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). Male albino rats (n = 40) were divided into four groups: control, LPS, SE, and CS-SENP. SE and CS-SENPs (5 mg/kg orally for 14 days) were given before LPS injection. Tissue architecture was assessed using histopathological analysis. HSP-47 and STEAP-3 protein expression levels were measured using ELISA, and oxidative stress markers were quantitatively evaluated. The expression of HO-1, TLR-4, STAT-3, TRAF-6, and IL-17A was measured using immunohistochemical analysis. Furthermore, HSP-90 expression was evaluated by immunofluorescence labeling. Results: CS-SENP characterization revealed uniform (PDI = 0.125 ± 0.04) nanoparticle size (108.54 ± 2.24 nm), with high zeta potential (+63.92 ± 6.287 mV), attributed to the CS layer, which was confirmed by FTIR and TEM as an electron-lucent halo enveloping the individual SENP cores. CS-SENPs significantly reduced lipid peroxidation (MDA) and restored glutathione (GSH) more effectively than SE. CS-SENPs improved redox (upregulated HO-1) and iron balance (downregulated STEAP-3), and also increased the anti-inflammatory effect (suppressed TLR-4, IL-17A, TRAF-6, and STAT-3). CS-SENPs showed superior antifibrotic efficacy (suppresses stress proteins, HSP-47 and HSP-90). Rats treated with CS-SENPs had nearly normal liver structure. Conclusions: The results concluded that CS-SENPs had superior and multi-targeted hepatoprotection against LPS-induced liver damage. Full article

Skin aging is characterized by fibroblast senescence, extracellular matrix (ECM) degradation, and impaired wound healing, driven by oxidative stress and telomere dysfunction. Here, we investigated the anti-aging effects of a standardized microwave-assisted propolis extract (MAPE) in both H₂O₂-induced and replicative senescence models of human dermal fibroblasts (HDFs). MAPE significantly reduced reactive oxygen species (ROS) accumulation and enhanced antioxidant gene expression (NQO1, GCLM), indicating activation of NRF2-dependent defense pathways. It suppressed senescence markers (CDKN2A, CDKN1A, IL6), decreased SA-β-gal activity, and attenuated inflammaging. Moreover, MAPE inhibited MMP1 expression, restored COL1A1, and improved fibroblast wound closure, thereby maintaining ECM homeostasis. Importantly, MAPE modulated Wnt/β-catenin signaling by upregulating WNT3A and LEF1 while suppressing DKK1, and increased TERT expression, suggesting involvement of telomerase-related regulatory pathways. These effects resembled those of CHIR99021, a canonical Wnt activator, while providing additional antioxidant protection. Together, our findings suggest that MAPE is a propolis-derived bioactive ingredient that counteracts fibroblast senescence through coordinated modulation of NRF2 and Wnt/β-catenin–TERT signaling pathways, supporting its potential as a cosmeceutical ingredient for mitigating skin aging. Full article

The driven damped pendulum is a foundational model in nonlinear dynamics, with applications ranging from Josephson junctions to MEMS oscillators. Conventional dimensionless treatments obscure the common physical origin of damping and driving in the inertia coefficient. Here we restore this dependence and establish inertia as a master control parameter governing stability, resonance, and bifurcations. Through linear analysis and perturbation theory, we derive universal scaling laws revealing a fundamental dichotomy: quantities at resonance—peak amplitude and nonlinear frequency shift—are independent of inertia due to exact algebraic cancellation between the inertia dependence of the effective driving amplitude and effective damping coefficient. Off resonance, however, amplitude scales inversely with inertia, bandwidth narrows proportionally, and the bistability threshold exhibits an even steeper dependence. A critical inertia separates underdamped from overdamped regimes, yielding non-monotonic relaxation times that maximize attractor memory at extreme inertia values. These scaling laws provide design guidelines: low inertia promotes broadband response for energy harvesting; high inertia suppresses off-resonant vibrations for precision timing and quantum applications. By establishing inertia as a physically realizable path through parameter space, this work unifies disparate phenomena and provides a framework for understanding stability in inertial-driven systems. Full article

Urban riverfronts, as integral components of the urban built environment, serve as essential blue–green infrastructure that offers restorative opportunities to residents in high-density areas. However, the mechanisms through which specific spatial qualities influence well-being outcomes remain underexplored. Guided by Attention Restoration Theory (ART) and Stress Recovery Theory (SRT), this study investigates the associations among spatial perception, perceived restorativeness, environmental sensitivity, and subjective well-being along the Yangtze Riverfront in Nanjing, China. A cross-sectional survey (N = 551) was conducted across six riverfront segments, using a 96-item questionnaire to assess five spatial perception dimensions, four restorativeness dimensions, and four well-being dimensions. Structural equation modeling (SEM) results indicate that spatial perception is positively associated with perceived restorativeness (β = 0.320, p < 0.001), with aesthetic perception demonstrating the strongest relative contribution (β = 0.265). Perceived restorativeness, in turn, significantly contributes to well-being (β = 0.540, p < 0.001), partially mediating the relationship between spatial perception and well-being (indirect effect (β = 0.173; 41.69% of total effect). Notably, environmental sensitivity moderated the spatial–restorative link (β = 0.799, p < 0.001), with restorative benefits being significantly amplified for individuals with higher sensitivity. These findings highlight aesthetics, accessibility, and perceived safety as priority targets for urban design. This study offers actionable insights for optimizing riverfront landscapes as vital urban health resources. Full article

Hyperuricemia is associated with liver dysfunction, yet its molecular mechanisms remain unclear. This study investigated high uric acid (HUA)-induced hepatocyte injury using a hyperuricemia mouse model (HUM) and uric acid (UA)-treated L02 cells. HUM exhibited elevated aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and pathological liver changes. Transmission electron microscopy (TEM) confirmed ferroptotic hallmarks, including mitochondrial shrinkage and increased membrane density. UA exposure upregulated NADPH oxidase 4 (NOX4), increased reactive oxygen species (ROS), and promoted lipid peroxidation (LPO), accompanied by intracellular Fe²⁺ accumulation. Mechanistically, UA increased hypoxia-inducible factor-2α (HIF-2α) expression, subsequently upregulating iron transporters divalent metal transporter 1 (DMT1) and transferrin receptor (TFRC). Deferoxamine (DFO) treatment effectively reversed Fe²⁺ overload and alleviated oxidative stress. Notably, pharmacological inhibition or genetic knockdown of HIF-2α specifically suppressed DMT1 upregulation and restored iron homeostasis, while TFRC expression remained unaffected. Blocking the HIF-2α/DMT1 axis significantly reduced LPO and mitochondrial dysfunction. These findings demonstrate that HUA induces hepatocyte ferroptosis through HIF-2α-mediated DMT1 upregulation, leading to Fe²⁺ overload and mitochondrial impairment. This study identifies the HIF-2α/DMT1 pathway as a key driver of HUA-induced liver injury and a potential therapeutic target. Full article

Background: As the body’s first line of defense against environmental stressors, the skin is highly susceptible to UVB-induced damage, which triggers inflammation and impairs barrier function. This study investigates the protective effects of safflower seed oil (SSO) and fermented Artemisia annua oil (FAAO) against UVB-induced skin injury. Methods: The protective effects of SSO and FAO against UVB irradiation was first tested in HaCaT keratinocyte. Subsequently, a UVB-irradiated SKH-1 mouse model was established to evaluate these two oils. RNA-seq analysis was employed to investigate the potential molecular mechanisms by which SSO and FAO repair the skin barrier. Results: In vitro experiments demonstrated that SSO (0.25%) and FAAO (0.1%) significantly enhanced HaCaT keratinocyte viability following UVB exposure while selectively modulating pro-inflammatory cytokine production. In a UVB-irradiated SKH-1 mouse model, standalone SSO or FAAO treatment partially ameliorated epidermal hyperplasia and restored UV-reduced collagen content, while the 1:1 SSO/FAAO combination exhibited superior efficacy in restoring skin architecture, reducing erythema and edema, and suppressing immune cell infiltration. Transcriptomic profiling revealed that the combined treatment promoted structural repair by attenuating inflammatory responses and preserving extracellular matrix homeostasis. Conclusions: Together, these findings underscore the potential of SSO/FAAO as a multifunctional botanical intervention for mitigating UVB-induced cutaneous damage. Full article

Adiponectin is adipokine exhibiting beneficial metabolic action through lipid and carbohydrate metabolism stimulation, as well as anti-inflammatory action. We have determined the role of adiponectin in gastroprotection against the formation of acute gastric lesions induced by ischemia–reperfusion (I/R). Gastric lesions evoked by I/R are a serious clinical entity; however, the participation of reactive oxygen species (ROS) and lipid peroxidation products and the involvement of nitric oxide (NO), neuropeptides released from sensory afferent nerves, and the hormone gastrin in the potential gastroprotective action of adiponectin remains unknown. Therefore, we determined the interplay between capsaicin-sensitive afferent nerves, the NO/NOS system, lipid peroxidation products, and the expression of pro-inflammatory and antioxidative factors in the gastroprotective action of adiponectin against gastric I/R. injury. Wistar rats was administered with adiponectin in graded doses (1–40 μg/kg i.v.) with or without: (a) blockade of nitric oxide (NO) activity by L-nitro-L-arginine (L-NNA) and (b) deactivation of sensory nerves by capsaicin (125 mg/kg s.c. 10 days before experiment conduction). They were then exposed to 30 min of ischemia by clamping of the celiac artery followed by 3 h of reperfusion after clamp release. After 3 h, the rats were euthanized with pentobarbital and their gastric blood flow (GBF) was determined by laser Doppler flowmetry, their blood was withdrawn to assess plasma gastrin levels, and the area of gastric lesions was measured by planimetry. Gastric biopsy samples were excised to determine gastric mucosal levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). In separate groups of animals with chronic gastric fistula, the effect of adiponectin on gastric acid secretion was determined. Adiponectin dose-dependently reduced the gastric lesions induced by I/R and this effect was accompanied by an increase in GBF. Blockade of NO-synthase with L-NNA (20 mg/kg i.p.) reversed the protective effect and the rise in GBF induced by this adipokine, and both these effects were restored when L-arginine was added to L-NNA. Capsaicin denervation also impeded the beneficial action of adiponectin in rats, but these effects were in part restored when exogenous CGRP was combined with adiponectin. Adiponectin dose-dependently decreased gastric acid secretion, the expression of mRNA for pro-inflammatory cytokines, and MDA plus 4-HNE content, while significantly increasing SOD, GSH and plasma gastrin increments. We conclude that adiponectin exerts gastroprotection against I/R-induced gastric lesions, through mechanisms involving NO and neuropeptides such as CGRP being released from sensory nerves, a decrease in lipid peroxidation (MDA+4-HNE), an increase of antioxidative factors (SOD, GSH), and the inhibition of gastric acid secretion. Full article

The spatiotemporal evolution of landscape patterns represents the most direct manifestation of land use change and remains a pivotal focus within landscape ecology research. Taking Huangshan City—a typical mountainous tourism city—as the study area, this research systematically analyzes the spatiotemporal evolution characteristics and driving mechanisms of landscape patterns over the past three decades. Based on land use data from 1992, 2002, 2012, and 2022, the study employs an integrated methodological framework including land use transition matrices, landscape pattern indices, moving window analysis, and the geographical detector (Geodetector) model, supported by ArcGIS and FRAGSTATS platforms. The results indicate that (1) during the study period, the landscape structure in Huangshan City exhibited a general trend characterized by “a stable foundation of forest land, continuous contraction of cropland, and significant expansion of construction land.” (2) From 1992 to 2012, cropland served as the primary source of transfer, mainly being converted into forest land; conversely, between 2012 and 2022, the reciprocal transformation between cropland and forest land became the dominant transition process. (3) At the landscape level, overall diversity enhanced and spatial distribution tended toward uniformity, whereas landscape fragmentation persisted in localized areas. (4) The driving force analysis revealed that “distance to the urban center” was the primary driving factor shaping landscape pattern changes, with its explanatory power continuously increasing. Furthermore, significant synergistic enhancement effects were observed between natural and socio-economic factors. These findings provide a scientific basis for ecological protection, restoration, and sustainable development strategies in Huangshan City within the context of rapid urbanization and tourism development. Full article

Cognitive impairment in schizophrenia remains insufficiently addressed by existing treatments. Current FDA-approved therapies primarily modulate neurotransmitter systems, resulting in incomplete symptom control and substantial adverse effects. There is therefore a critical need for therapeutic strategies that more directly address the intracellular signaling mechanisms underlying synaptic dysfunction and cognitive deficits in schizophrenia. Protein phosphatases represent an essential but historically underexplored class of signaling enzymes that regulate phosphorylation-dependent control of synaptic receptor trafficking, plasticity, and neuronal circuit function. Although multiple phosphatases have been implicated in schizophrenia through genetic, post-mortem, and functional studies, their therapeutic targeting has been limited by challenges related to selectivity, cellular permeability, and pleiotropy. Here, we review the etiology of schizophrenia and limitations of current pharmacological approaches, synthesize evidence linking specific protein phosphatases to schizophrenia pathophysiology, and discuss emerging strategies, including allosteric modulation and targeted protein degradation, that may enable selective intervention in phosphatase-driven signaling pathways. We highlight the striatal-enriched tyrosine phosphatase STEP (PTPN5) as a case study illustrating how selective phosphatase modulation can restore synaptic signaling in schizophrenia-relevant models. Full article

The silkworm, Bombyx mori (Bm), is an insect that contributes to industries such as silk production, cosmetics, medicine, and food, as well as to scientific research. A previous study showed that Bm odorant receptor (BmOr) genes, BmOr44, BmOr54, and BmOr63, may play a major role in oviposition. This research aimed to investigate the function of these three genes using a double-stranded RNA (dsRNA) technique to knock down their expression levels. Our results revealed that the gene-specific dsRNAs could moderately reduce the expression levels of BmOr44, BmOr54, and BmOr63 in the silk moth antenna. Silk moths were injected with 50 nM dsRNABmOr54 and 100 nM dsRNABmOr63 and showed relative oviposition rates under the mulberry leaves condition at 111.45% and 109.58%, respectively, when compared to those with dsRNAlacZ injection. The reduction in expression levels of these three genes showed no effect on the oviposition rates of the silk moths without mulberry leaves treatment. The expression levels of these BmOr genes were restored after fertilization, suggesting the temporary effects of the dsRNAs. Our findings suggested that variation in BmOr54 expression level was correlated with changes in oviposition behavior in Bombyx mori. Full article

Bacillus coagulans has attracted widespread attention in the treatment of irritable bowel syndrome due to its multiple probiotic functions, yet its specific molecular mechanisms remain unclear, and the efficacy of probiotics exhibits significant strain specificity, posing a key bottleneck for practical application. To address this, this study obtained a bile salt-tolerant B. coaguans idrc019 through in vitro screening. This strain demonstrated strong survival and germination in simulated gut conditions, supporting effective intestinal colonization. Further evaluation in an IBS animal model revealed that idrc019 alleviated visceral hypersensitivity and colonic inflammation in a dose-dependent manner. Through enhanced intestinal barrier integrity, microbiota modulation (e.g., Actinobacteria restoration), and elevated metabolites (e.g., kynurenine), the strain exerted IBS-alleviating effects via synchronized immune, microbial, and metabolic regulation. Our findings offer a mechanistically grounded probiotic candidate, underscore functional screening as a critical strategy, and pave the way for clinical application. Full article

CAD/CAM polymer-based dental materials are increasingly used as metal-free alternatives for fixed and implant-supported restorations. High-performance polymers such as polyetheretherketone (PEEK), fiber-reinforced composites, and graphene-reinforced polymers have been introduced to improve material stability; however, evidence regarding the effects of thermal aging on their physicochemical and biological properties remains limited. In this study, PEEK, a fiber-reinforced composite (FRC), and a graphene-reinforced PMMA-based polymer (G-CAM) were evaluated. Twenty-seven disc-shaped specimens (10 × 2 mm; n = 9 per material) were fabricated and subjected to 10,000 thermal cycles between 5 and 55 °C. Color change (ΔE₀₀), surface roughness (Ra), and Vickers microhardness (VHN) were measured before and after aging. Chemical stability was assessed using FTIR and Raman spectroscopy, surface morphology by SEM analysis, and biological safety by cytotoxicity testing. Material-dependent differences were observed in color stability, surface roughness, and microhardness after thermal aging (p < 0.05). Microhardness decreased in the fiber-reinforced and graphene-reinforced materials, whereas PEEK showed no significant change. Spectroscopic analyses indicated preserved chemical structure, and all materials demonstrated acceptable cytocompatibility. Thermal aging influenced material behavior while chemical stability and biological safety were maintained, highlighting the importance of considering aging behavior during material selection for prosthetic restorations. Full article