Search Results (7,383)

Incretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have emerged as potentially promising therapeutic agents for improving ovarian function, especially in women with polycystic ovary syndrome (PCOS) and obesity-related reproductive dysfunction. This comprehensive review synthesizes evidence from 30 highly relevant studies examining the mechanisms of action, clinical outcomes, and safety profile of incretin therapies on ovarian function. The evidence suggests that GLP-1 RAs may exert beneficial effects through multiple molecular pathways, including FOXO1 signaling, modulation of steroidogenesis, and enhancement of insulin sensitivity, although most mechanistic data derive from animal models and in vitro studies without validation in human ovarian tissue. Clinical outcomes from randomized controlled trials and meta-analyses show improvements in menstrual regularity, hormonal profiles, and spontaneous conception rates, though evidence certainty is limited by small sample sizes, short duration, high heterogeneity, and restriction to overweight/obese populations. While preliminary safety data regarding inadvertent early pregnancy exposure are reassuring, animal studies suggest potential dose-dependent risks that warrant careful consideration. Importantly, GLP-1 RAs are not currently approved or guideline-recommended for fertility restoration, and substantial uncertainty remains regarding long-term reproductive safety, optimal patient selection, and clinical guidelines. This review provides a balanced synthesis of current evidence and identifies critical gaps requiring further investigation before routine clinical use can be recommended. Full article

Background/Objectives: Rotenone (RT)-induced neurotoxicity is widely used to model Parkinsonism-like nigrostriatal injury and recapitulates several PD-relevant pathological features, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and dopaminergic neurochemical disturbance. Loganin (LG), an iridoid glycoside isolated from Cornus officinalis, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective properties. However, its protective effects in a unilateral stereotaxic RT lesion model have not been fully elucidated. This study aimed to investigate the neuroprotective potential of LG against RT-induced Parkinsonism-like pathology in rats and to explore the possible involvement of antioxidant-related signaling mechanisms. Methods: Adult male Wistar rats were randomly assigned to twelve experimental groups (n = 8/group), including control, sham, RT, sham + LG, RT + LG, RT + trigonelline (TG) + LG, and RT + selegiline (SL). RT was stereotaxically injected once into the right substantia nigra pars compacta (SNpc) on Day 0 to induce unilateral nigrostriatal injury. LG was administered orally once daily from Day 1 to Day 21 at doses of 3, 10, and 30 mg/kg. TG was given intraperitoneally 30 min before LG treatment, while SL served as a reference antiparkinsonian drug. Behavioral assessments and biochemical analyses were conducted to evaluate motor dysfunction, oxidative and nitrosative stress, endogenous antioxidant status, mitochondrial dysfunction, inflammatory and apoptotic responses in the SNpc, and striatal catecholamine disturbances. Results: RT lesioning produced significant motor deficits, oxidative and nitrosative stress, depletion of endogenous antioxidant defenses, mitochondrial dysfunction, inflammatory and apoptotic activation in the SNpc, and abnormalities in striatal catecholamine levels. LG treatment significantly attenuated these pathological changes, with more pronounced protective effects observed at 10 and 30 mg/kg. Co-administration of TG partially weakened the beneficial effects of LG, suggesting the possible involvement of antioxidant defense-related signaling while not providing direct proof of a single pathway. SL also ameliorated RT-induced behavioral and biochemical abnormalities. Conclusions: These findings suggest that LG confers multi-target neuroprotective effects against RT-induced Parkinsonism-like features in rats. The protective actions of LG were associated with attenuation of oxidative stress, mitochondrial dysfunction, neuroinflammation, apoptosis, and catecholaminergic disturbances. Because the pathway analysis remains pharmacological and indirect, additional studies using direct molecular validation are warranted before LG can be considered a disease-modifying candidate for PD-related neurodegeneration. Full article

Ischemic stroke is an acute cerebrovascular disease with high disability and morbidity. However, therapeutic approaches are restricted by a narrow time window for reperfusion. Astilbin has various pharmacological activities and good therapeutic potential against ischemic stroke and neurodegenerative diseases. Nevertheless, Astilbin’s mechanism of action remains unclear. Here, we used an integrated strategy that includes network pharmacology, omics validation, and functional verification. Potential targets of Astilbin were predicted using SwissTargetPrediction and PharmMapper, and cross-analyzed with IS-related genes from multiple databases. GO/KEGG enrichment analyses showed that Astilbin synergistically regulates stroke-associated pathways (e.g., MAPK, AGE-RAGE). Combined transcriptomic and metabolomic assays confirmed that Astilbin ameliorates OGD/R-induced oxidative stress and metabolic disorders by modulating the MAPK and ferroptosis pathways. Molecular docking and dynamics simulations revealed that Astilbin has high affinity for core targets (ERK1/2, CREB, p90RSK, MMP9) and binds stably to MMP9. Using an OGD/R-injured neuronal-like PC12 cell line, in vitro assays confirmed that Astilbin alleviates oxidative stress, calcium overload, lipid peroxidation, and intracellular iron levels, while also modulating apoptosis- and inflammation-related genes. Overall, this study has established a comprehensive pharmacological framework for the use of Astilbin against IS, clarified its multi-target, multi-pathway neuroprotective mechanisms of action, and provided evidence for its potential in the treatment of IS. Full article

Urban reservoirs are increasingly exposed to multiple interacting pressures associated with eutrophication, pollutant inflow, ageing sewerage and stormwater infrastructure, and climate-related hydrological instability. This issue is of growing concern because municipalities often possess fragmented monitoring and planning evidence without an operational framework for translating it into remediation action. This study develops an integrated decision-support framework for the Ternopil Reservoir based primarily on recent hydrochemical monitoring data, complemented by historical targeted sampling and local environmental and planning materials. The analysis focuses on the most informative indicators of ecological deterioration in an urban reservoir, including oxygen regime, organic pollution, nutrient-related parameters, suspended solids, and selected pollution markers. The available evidence indicates that the Ternopil Reservoir is among the most environmentally stressed water bodies within the local reservoir system, with recurrent eutrophication symptoms, seasonal water blooming, and spatially differentiated exceedances of selected water-quality indicators. The results further indicate persistent nutrient-related and organic pressure, pronounced hydrochemical tension in 2022, and hotspot vulnerability in hydraulically weak sectors of the reservoir. To address these pressures, the study proposes a four-stage monitoring-to-remediation framework that links environmental diagnosis with the identification of vulnerable zones, the prioritisation of hydraulic and hydrobiological measures, and post-remediation control. The proposed framework is intended as an operational planning tool for translating fragmented local evidence into a coherent remediation pathway for urban reservoirs under multiple environmental stressors. Full article

Climate change poses accelerating and intensifying threats to cultural heritage worldwide, necessitating urgent and coordinated state-level responses. This study critically examines China’s governance framework for climate adaptation of cultural heritage, identifying a critical policy misalignment: although relevant legal and governance instruments—spanning cultural heritage protection, environmental governance, disaster risk reduction, territorial spatial planning, and climate action systems—are nominally in place, they remain profoundly fragmented in practice, resulting in operational inefficiency that severely constrains effective adaptation. To address this, the paper argues for a fundamental paradigm shift from static preservation to dynamic adaptation. It proposes a reform pathway centered on three pillars: reconceptualizing heritage from static preservation to dynamic adaptation, institutionalizing cross-departmental cooperation, and integrating systemic adaptation tools into planning and decision-making. The ultimate objective is to establish an adaptive governance system capable of responding flexibly to climate impacts through interdisciplinary coordination. This transformation is framed as a critical strategic imperative, essential for ensuring the long-term resilience of cultural heritage and civilizational continuity in a warming world. Full article

Virtual reality heritage experiences can be understood as multisensory interaction systems, yet how auditory, haptic, and gestural cues combine at the system level to shape electronic word-of-mouth (eWOM) intention remains insufficiently understood. Addressing this problem from a configurational systems perspective, this study applies fuzzy-set qualitative comparative analysis (fsQCA) to five auditable interaction cues (acoustic clarity, rhythmic drive, vibrotactile actuation level, gesture complexity, and compound gesture frequency) across a set of widely used VR cultural heritage applications. The results identify two sufficient system-level pathways to high eWOM intention: a rhythm-driven, low-burden pathway and a coordination-driven pathway characterized by clearer audio, stronger rhythmic structure, and tighter haptic and gestural action closure. Low eWOM intention is most consistently associated with weak cue interpretability, limited temporal drive, or unbalanced stimulation patterns, suggesting that isolated enhancement of single channels does not reliably translate into downstream sharing intentions. These findings reposition VR heritage design as a problem of configuring coherent multisensory interaction systems rather than maximizing individual stimuli. The study contributes a bounded, case-comparative account of how auditable cue bundles shape eWOM intention and offers system design guidance for resource-sensitive multisensory coordination in VR heritage applications. Full article

Caffeic acid (CA) is a phenolic compound commonly found in fruits, vegetables, and coffee, with preclinical evidence demonstrating its important role in disease management through different mechanisms of action. This review aimed to explore CA’s pharmacological effects in different pathological conditions, and sources were retrieved by using databases like PubMed, Scopus, Google Scholar, and Web of Science and based on preclinical studies. CA notably protects cells and tissues from oxidative stress and inflammation, highlighting its therapeutic role in the management of pathogenesis. The neuroprotective, cardioprotective, hepatoprotective, anti-microbial, and anti-obesity effects are reported through in vitro and in vivo studies. Moreover, its anticancer effects are linked to modulation of cell signaling pathways, together with angiogenesis, cell cycle, apoptosis, and the PI3K/Akt pathway. This article explores how caffeic acid influences health conditions, providing a comprehensive overview of its effects on disease processes. Reviewing the literature aims to enhance the understanding of caffeic acid’s role in disease management and as a natural therapeutic agent. Although several studies demonstrate the anticancer effects and its role in the management of various pathological conditions, most of the existing evidence is based on in vitro, in vivo, and xenograft models. Moreover, many natural compounds, including CA, that exhibit activity in preclinical settings fail to translate into clinical applications, due to restrictions of poor bioavailability, toxicity, rapid metabolism, and differences in the tumor microenvironment. Thus, future studies should emphasize well-designed in vivo studies as well as controlled clinical trials to better describe CA’s safety, efficacy, mechanism of action, and therapeutic application in humans. Further investigation of its interactions with other therapeutic agents may offer insights into synergistic effects that enhance treatment efficacy. Overall, a more comprehensive understanding of this compound will be indispensable for its development as a therapeutic agent in the treatment of chronic disease. Full article

Wood vinegar is a naturally acidic liquid produced during the pyrolysis of agricultural and forestry residues, which contains a complex mixture of bioactive components, including organic acids, phenolics, ketones and so on. As a multifunctional biomass-derived product with considerable potential, wood vinegar has attracted widespread attention in agroforestry and environmental research. This review summarizes recent research progress on the roles of wood vinegar in plant disease resistance, plant growth promotion, and soil improvement. The inhibitory effects of wood vinegar against various plant pathogens and the potential mechanisms involved are discussed, as well as two major pathways through which wood vinegar promotes plant growth. In addition, the roles of wood vinegar in improving soil fertility are examined, particularly through regulating soil salinity and enhancing soil chemical and biological properties. Recent advances in its practical applications across different agricultural fields are also summarized, and safety considerations associated with its use are analyzed. Despite these advances, current studies remain largely focused on phenomenological observations, with limited investigation in forestry applications. Furthermore, the molecular mechanisms underlying the biological activities of wood vinegar and the long-term ecological risks associated with repeated applications remain insufficiently understood. This review provides perspectives on further exploration of the mechanisms of action of wood vinegar and the potential risks associated with its long-term application, with the aim of providing a scientific reference for the safe and efficient utilization of wood vinegar in sustainable agriculture and ecological restoration. Full article

To achieve both a high material removal rate and excellent surface quality, this paper proposes a solid-phase Fenton chemo-mechanical lapping (SF-CML) method. Using high-purity type 316 stainless-steel as the research object, a solid lapping tool containing Fe₃O₄ microparticles was employed in synergy with an H₂O₂-based slurry. Under locally high-pressure and high-temperature conditions, Fe²⁺ ions are released, which in turn catalyze the generation of highly reactive hydroxyl radicals (·OH). These radicals promote the formation of an oxide layer on the workpiece surface, which is continuously removed through mechanical action. The results show that at pH 2.5 and an H₂O₂ concentration of 0.05 wt%, SF-CML achieves the best processing performance, with an MRR of 16.64 μm/min and a Sa as low as 20.95 nm. XPS, EPR, and other characterization methods collectively provided evidence for the oxidation of the sample surface and the existence of ferrous ions and hydroxyl radicals in the slurry, thereby confirming the effectiveness of the solid-phase Fenton reaction. Compared with conventional homogeneous Fenton CMP and pure mechanical lapping, SF-CML not only significantly improves removal efficiency but also effectively enhances surface quality. This method avoids the problems of easy precipitation and low removal efficiency commonly encountered in traditional homogeneous Fenton systems, providing a new technical pathway for high-efficiency precision processing of metallic materials. Full article

This study developed high-oxygen-barrier active bilayer packaging films by combining corona-treated low-density polyethylene (LDPE) with chitosan/glycerol (CS/Gl) and carvacrol@natural zeolite (CV@NZ) nanohybrid layers using industrially scalable processes. LDPE film was surface-activated via ambient-pressure corona treatment (0.75 s/cm² at 45 kV, 30 W) and assembled with solution-cast CS/Gl or CS/Gl/CV@NZ monolayers via hot-pressing (110 °C, 1 min). Corona treatment enabled robust interfacial adhesion, evidenced by statistical equivalence between monolayer and bilayer mechanical properties. Incorporation of 10 wt.% CV@NZ nanohybrid increased elastic modulus by 60% (to ≈2970 MPa) and tensile strength by 30% (to ≈50 MPa). The LDPE-CS/Gl film achieved a 64-fold reduction in oxygen permeability; CV@NZ incorporation maintained excellent barrier performance (22-fold reduction). Antioxidant potency increased 16-fold upon CV@NZ incorporation. The LDPE-CS/Gl/CV@NZ film demonstrated exceptional antibacterial activity (5.08–5.30 log reductions; >99.999% kill) against both Listeria monocytogenes and Escherichia coli—substantially exceeding additive effects—confirming synergistic action between chitosan and carvacrol. In fresh minced pork preservation (8 days, 4 °C), the active film achieved a 1.73 log reduction in Total Viable Count (98.2% inhibition) and extended microbiological shelf life from 6 to beyond 8 days (33% increase). The bilayer configuration utilizes only 40% of the total thickness as biopolymer, aligning with circular economy principles. Unlike conventional high-barrier films (e.g., PA/PE) which require complex compatibilization for recycling, the water-soluble chitosan layer in this bilayer design can be readily separated from the LDPE backbone, enabling recovery of a pure polymer stream. This work demonstrates a feasible pathway for developing next-generation active packaging that combines a high oxygen barrier, potent antioxidant activity, and exceptional antimicrobial efficacy through industrially scalable manufacturing. Full article

This study examines smart technology adoption in foodservice microbusinesses by moving beyond intention-based explanations to examine how adoption and post-adoption unfold in practice. Hospitality technology research has largely emphasised attitudes and behavioural intentions, offering limited insight into how technologies become embedded in everyday operations, particularly in resource-constrained microbusiness contexts. Focusing on foodservice microbusinesses in Malaysia, this study goes beyond pre-adoption intention and examines the nuances of actual technology implementation, guided by adaptive training as the central adoption-enabling mechanism. Using an action research approach, this study implemented a one-month adaptive training intervention that enabled operators to engage in hands-on, experiential learning within their own business environments. The findings uniquely indicate that technology adoption is shaped by capability asymmetry, with differences in technological literacy, prior experience, and resources producing varied adoption pathways. These differences were addressed through adaptive training that aligned the pace and intensity of learning with operators’ capabilities. This study also identifies specialist mediation as a key mechanism supporting adoption, as guidance from a knowledgeable intermediary reduced complexity, facilitated learning, and enabled the transfer of trust. The findings suggest that smart technology adoption in microbusiness settings is not only a matter of intention but also a situated learning process shaped by unequal capabilities, adaptive training, and specialist-guided trust formation. Full article

Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), arise from highly interconnected molecular and cellular abnormalities that progressively lead to neuronal dysfunction, synaptic failure, and cell death. This review provides a unified framework to understand the interrelated molecular mechanisms driving these diseases, with a focus on identifying key disease-specific intervention nodes. Core contributors include oxidative stress, mitochondrial dysfunction, protein aggregation, neuroinflammation, and emerging roles of peroxisomal dysfunction in redox imbalance, lipid dysregulation, and inflammatory amplification. Single-target therapies often show limited efficacy due to the complex, interconnected nature of these pathways. In contrast, polypharmacology, which targets multiple disease-relevant mechanisms simultaneously, offers a more promising therapeutic strategy. This review critically examines how pathway crosstalk drives neurodegenerative progression, with particular emphasis on mitochondrial–ROS–inflammatory signaling, aggregation–proteostasis failure, synaptic–neuroimmune dysfunction, and gut–brain communication. It evaluates various multi-node intervention strategies, including multi-target-directed ligands (MTDLs), molecular hybrids, natural products, drug repurposing, and nanocarrier-based delivery systems. Advances in network pharmacology, artificial intelligence (AI), bioinformatics, and multi-omics have enhanced the identification of actionable therapeutic nodes, candidate compounds, and brain-targeted delivery platforms. Notably, the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome and cyclic GMP–AMP synthase (cGAS)—stimulator of interferon genes (STING) pathways—play distinct roles in neuroinflammation, amplifying neuronal damage by releasing inflammatory cytokines and inducing mitochondrial dysfunction. However, successful translation into clinical practice remains constrained by challenges such as blood–brain barrier penetration, patient heterogeneity, and biomarker limitations. The review advocates for a shift towards mechanism-informed, patient-stratified polypharmacological strategies to better address the network pathology of neurodegeneration, despite significant translational hurdles. Full article

The bark of Myrica rubra (Lour.) Siebold & Zucc (M. rubra) is a natural remedy widely used in China and other Asian countries to treat tissue and bone injuries, burns, scalds, gastrointestinal ulcers, and diarrhea. Myricanol is an important ingredient in the bark of M. rubra. This review summarizes articles published over the past 26 years on the pharmacological effects and mechanisms of action of myricanol, aiming to advance research and applications of myricanol. Evidence shows that myricanol has multiple bioactive properties, including antioxidant, anticancer, anti-inflammatory, antimicrobial, antidiabetic, and antihyperlipidemic effects. Myricanol improves metabolic abnormalities in mice by activating the AMPK/SIRT1/PGC-1α signaling pathway. It also demonstrates significant anticancer, antioxidant, and anti-inflammatory actions, primarily by regulating Caspase and BCL-2 family proteins, inhibiting iNOS expression, scavenging free radicals, and interacting with Peroxiredoxin 5. Therefore, myricanol shows great potential for the treatment of cancer, metabolic abnormalities, and inflammatory bowel disease. Further research is needed to improve its bioavailability, confirm its pharmacological effects and mechanisms in vivo, and explore its pharmacokinetic properties and safety. Full article

Background/Objectives: Trigeminal neuralgia (TN) is a debilitating neurological condition characterized by recurrent, severe pain linked to peripheral and central sensitization within trigeminal pathways. Current pharmacologic treatments are limited by inadequate efficacy or dose-limiting side effects, and botulinum neurotoxin type A (BoNT/A) has emerged as a viable option. However, its potential use in the management of TN is hampered by methodological limitations in existing studies and a lack of pivotal clinical trials. This study investigated the efficacy, optimal treatment site, preventive utility, and duration of effect of incobotulinumtoxinA (Inco/A), a BoNT/A, in a model of TN. Methods: An infraorbital nerve chronic constriction injury model was used to induce mechanical allodynia in male Sprague–Dawley rats, reproducing the trigeminal sensitization seen in TN. The effects of subcutaneous Inco/A (1, 2, and 4 U) were measured using the mechanical sensitivity (von Frey) test to evaluate the dose response, effect of injection location, potential preventive nature of treatment, and duration of benefit. Results: Inco/A produced a robust, dose-dependent reduction in mechanical allodynia, predominantly via a local mechanism of action. Both preventive and therapeutic administration of Inco/A was efficacious, with significant reduction in allodynia even when administered up to 28 days before nerve injury. The anti-allodynic effect persisted up to 56 days post-injection. Conclusions: Inco/A is highly effective in alleviating mechanical allodynia in a validated rat model of TN. The findings highlight Inco/A as a promising candidate for clinical translation in TN and related neuropathic pain syndromes and support systematic investigation in well-controlled human trials. Full article

Calcium carbide slag is a highly alkaline solid waste generated during acetylene production, but its long-term accumulation causes land occupation and persistent environmental risks such as soil alkalinization and water pollution. To support circular economy and carbon emission reduction goals, in this study, we develop an integrated physical decontamination–mineralization process combining calcination, magnetic separation, sedimentation, and CO₂ mineralization. After calcination, magnetic separation, and 8 h of gravity sedimentation, the removal efficiency of Si reaches about 67% (residual Si content reduces to 0.43%), while those of Fe and Al are 75.4% and 74.2%, respectively. The purified calcium-rich slurry is then used for CO₂ mineralization. Under a solid-to-liquid ratio of 10% and a CO₂ flow rate of 0.4 L/min, CO₂ is fixed as carbonate solids, yielding calcite-type CaCO₃ with 97.88% ± 0.35% purity. This process is centered on physical separation and uses no acids, alkalis, or ammonium salts, avoiding secondary pollution while achieving waste valorization and permanent CO₂ sequestration. In this study, we provide a scalable, low-impact pathway for alkaline solid waste valorization and carbon emission reduction, contributing to sustainable consumption and production (SDG 12) and climate action (SDG 13). Full article