Search Results (64,865)

Phosphate is emerging as an active mediator of oxidative stress and vascular injury in chronic kidney disease (CKD). This emerging pathophysiological framework, referred to as “Phosphatopathy”, describes the systemic syndrome driven by chronic phosphate overload and characterized by oxidative stress, inflammation, endothelial dysfunction, vascular calcification, cellular senescence, and metabolic imbalance. Beyond being a biochemical marker, phosphate overload triggers NOX-derived reactive oxygen species (ROS), activates Wnt/β-catenin and TGF-β signaling, and disrupts the FGF23–Klotho axis, promoting endothelial dysfunction, vascular calcification, and left ventricular hypertrophy (LVH). These pathways converge with systemic inflammation and energy imbalance, contributing to the malnutrition–inflammation–atherosclerosis (MIA) syndrome. Experimental and clinical data reveal that the phosphate/urinary urea nitrogen (P/UUN) ratio is a sensitive biomarker of inorganic phosphate load, while emerging regulators such as microRNA-125b and calciprotein particles integrate phosphate-driven oxidative and inflammatory responses. Therapeutic strategies targeting phosphate burden—rather than serum phosphate alone—include dietary restriction of inorganic phosphate, non-calcium binders, magnesium and zinc supplementation, and activation of important pathways related to the activation of antioxidant defense such as AMP-activated protein kinase (AMPK) and SIRT1. This integrative framework redefines phosphate as a modifiable upstream trigger of oxidative and metabolic stress in CKD. Controlling phosphate load and redox imbalance emerges as a convergent strategy to prevent vascular calcification, improve arterial stiffness, and reduce cardiovascular risk through personalized, mechanism-based interventions. Full article

Background/Objectives: This study aimed to perform a comparative analysis of the original Viagra^® product and sildenafil-containing tablets obtained from illegal sources (the darknet). Specifically, the analyzed material consisted of samples seized by Polish law enforcement authorities from unverified vendors operating within the Central European darknet market. The study utilized thermal methods, specifically Thermogravimetry (TG), Derivative Thermogravimetry (DTG), and calculated Differential Thermal Analysis (c-DTA), as well as colorimetric analysis based on the International Commission on Illumination (CIE) L*a*b* system. Methods: Thermal analyses enabled the assessment of the thermal stability of the tested samples, identification of characteristic stages of thermal decomposition, and determination of differences in thermal behavior between the pure substance, the original preparation, and darknet samples. In turn, color measurements in the CIE L*a*b* space allowed for an objective comparison of tablet appearance and determination of the degree of color similarity to the original product. Results: The obtained results showed that only a few samples (V1, V3, V4, V6, V8) exhibited features similar to the original Viagra^®, both in terms of thermal profile and color. Most of the tested tablets were characterized by significant variability in physicochemical properties, indicating a lack of quality control and inconsistency in formulation. Samples V2 and V7 deviated particularly strongly—both thermally and visually—suggesting that they might not contain the original active substance or contained it in a different chemical form. Conclusions: The use of combined thermal and colorimetric methods proved to be an effective tool in the identification of counterfeit pharmaceutical products, enabling simultaneous evaluation of their composition and authenticity. The results confirm the validity of employing integrated physicochemical analyses for the detection of falsified medicines present on the illegal market. Full article

In the centralized scheduling mode of automated container terminals, Automated Guided Vehicles (AGVs) often experience decision-making delays caused by system information-processing bottlenecks, which significantly affect path-planning efficiency and are particularly evident in sudden-traffic scenarios. To address this issue, this paper incorporates the artificial potential field (APF) into the cost function of Model Predictive Control (MPC) and develops a dual-trigger mechanism for lane-change and lane-return MPC obstacle-avoidance framework (Event-Triggered Model Predictive Control, EMPC). This framework integrates an obstacle-triggered local optimization mechanism and a lane-change trigger, enabling AGV to perform autonomous and dynamically responsive local obstacle avoidance, thereby improving local path-planning efficiency. Furthermore, a Proximal Policy Optimization (PPO)-based strategy is introduced to adaptively adjust the obstacle-weighting parameters within the EMPC cost function, enhancing both obstacle-avoidance and lane-keeping performance. Under multi-lane overtaking conditions, a lane-change trigger—implemented as a dual-phase “lane-change–return” mechanism—is employed, in which lateral optimization is activated only during critical phases, reducing online computational load by at least 28% compared with conventional MPC strategies. The experimental results demonstrate that the proposed PPO–EMPC architecture exhibits high robustness, real-time performance, and scalability under dynamic and partially observable environments, providing a practical and generalizable decision-making paradigm for cooperative AGV operations in automated container terminals. Full article

Prolonged operation of cotton picker poses significant risks of work-related musculoskeletal disorders (WMSDs), primarily driven by non-ergonomic cab layouts that fail to accommodate the unique “left-hand steering, right-hand lever” operational mode. Traditional optimization methods, relying on general digital human models or isolated surface electromyography (sEMG) measurements, often lack the physiological fidelity and computational efficiency for high-dimensional, personalized design. To address this interdisciplinary challenge in agricultural engineering and ergonomics, this study proposes a novel AMS-RF-DBO framework that integrates high-fidelity biomechanical simulation with intelligent optimization. A driver–cabin biomechanical model was developed using the AnyBody Modeling System (AMS) and validated against sEMG data (ICC = 0.695). This model generated a dataset linking cab layout parameters to maximum muscle activation (MA). Using steering wheel and control lever coordinates (X, Y, Z) as inputs, a Random Forest (RF) regression model demonstrated strong performance (R² = 0.91). Optimization with the Dung Beetle Optimizer (DBO) algorithm yielded an optimal configuration: steering wheel (L1 = 434 mm, H1 = 738 mm, θ = 32°) and control lever (L2 = 357 mm, H2 = 782 mm, M = 411 mm), reducing upper-limb MA from 3.82% to 1.47% and peak muscle load by 61.5%. This study not only provides empirical support for ergonomic cab design in cotton pickers to reduce operator fatigue and health risks but also establishes a replicable technical paradigm for ergonomic optimization of other specialized agricultural machinery. Full article

Background: The retinoid X receptor (RXR) is a ligand-activated nuclear receptor that heterodimerizes with numerous partners to regulate diverse transcriptional programs. RXR agonists, including the FDA-approved drug bexarotene, show anti-tumor activity but are limited by adverse side effects. V-125 is a next-generation RXR agonist engineered for improved selectivity, pharmacokinetics, and reduced lipogenic effects. This study compares the molecular and functional effects of V-125 and bexarotene in HER2⁺ breast cancer models. Methods: Female MMTV-Neu mice bearing mammary tumors were treated with control, V-125 (100 mg/kg diet), or bexarotene (100 mg/kg diet) for 10 days. RNA sequencing was used to identify differentially expressed genes and pathways. Candidate targets were validated by qPCR and immunohistochemistry (IHC). Immune modulation was evaluated by IHC staining for CD8 cells and CD206⁺ macrophages in tumors to capture the tumor microenvironment. Functional assays in JIMT-1 human HER2⁺ cells assessed RXR target activation and clonogenic potential in tumor cells. Results: V-125 induced broader transcriptional changes than bexarotene, including selective upregulation of Nrg1, Nfasc, Lrrc26, and Chi3l1 genes associated with improved patient survival. Pathway analysis revealed regulation of immune activation, cancer signaling, and lipid metabolism. Both V-125 and bexarotene suppressed colony formation in JIMT-1 cells, confirming previous observations about RXR-dependent inhibition of tumor cell growth. Moreover, V-125 in vivo had distinct capabilities to increase CD8 cell infiltration and reduced CD206⁺ macrophages, whereas bexarotene did not. Conclusions: V-125 but not bexarotene reprograms tumor transcriptional programs and the immune landscape in an anti-tumor manner in the MMTV-neu mouse model and in in vitro models of HER2⁺ breast cancer. This highlights its promise as a selective RXR agonist with anti-tumor and immunomodulatory activity in HER2⁺ breast cancer. Full article

With the increasing penetration of distributed energy resources (DERs) and the rapid development of active distribution networks, the traditional centrally controlled operation mode can no longer meet the flexibility and autonomy requirements under the multi-dimensional coupling of sources, networks, loads, and storage. To achieve regional energy self-balancing and autonomous operation, this paper proposes a partitioned configuration method for energy storage systems (ESSs) in energy-autonomous distribution networks based on autonomous unit division. First, the concept and hierarchical structure of the energy-autonomous distribution network and its autonomous units are clarified, identifying autonomous units as the fundamental carriers of the network’s autonomy. Then, following the principle of “tight coupling within units and loose coupling between units,” a comprehensive indicator system for autonomous unit division is constructed from three aspects: electrical modularity, active power balance, and reactive power balance. An improved genetic algorithm is applied to optimize the division results. Furthermore, based on the obtained division, an ESS partitioned configuration model is developed with the objective of minimizing the total cost, considering the investment and operation costs of ESSs, power purchase cost from the main grid, PV curtailment losses, and network loss cost. The model is solved using the CPLEX solver. Finally, a case study on a typical multi-substation, multi-feeder distribution network verifies the effectiveness of the proposed approach. The results demonstrate that the proposed model effectively improves voltage quality while reducing the total cost by 20.89%, ensuring optimal economic performance of storage configuration and enhancing the autonomy of EADNs. Full article

Intermittent Hypobaric Storage (IHS) effectively inhibits postharvest deterioration of cassava roots, yet its physiological regulatory mechanisms and associated quality alterations remain poorly understood. This study investigated the regulatory mechanisms of root respiratory physiology under IHS and their impact on quality. Results indicate that IHS reduces root respiration rates and maintains generally low anaerobic respiration enzyme activity, while ATP content remains higher than in the control. This supports efficient energy supply for cellular metabolism, thereby delaying senescence. Transcriptomic analysis revealed that IHS modulates glycolytic genes, suppresses excessive anaerobic respiration, and upregulates pathways associated with ribosome biogenesis and oxygen response. Meanwhile, IHS downregulated ATP-consuming pathways involved in phenylpropanoid biosynthesis. IHS effectively prolongs shelf life and preserves the nutritional quality of cassava roots, maintaining levels comparable to those of fresh roots. These molecular responses collectively support the physiological and biochemical benefits of IHS, providing valuable insights for optimizing its application in cassava postharvest storage. Full article

Peripheral nerve repair remains a major clinical challenge, and novel strategies such as conduit-assisted repair have been developed to improve outcomes. In this study, we fabricated a 3D-printed nerve guidance conduit (NGC) composed of polycaprolactone (PCL), a biocompatible and biodegradable polymer, combined with acellular dermal matrix (ADM) derived from porcine dermis, in order to create a multilayered PCL–ADM NGC with both favorable mechanical properties and biological activity. Twenty rabbits were divided into four groups: a negative control group, a silicone tube repair group, an autologous nerve graft group, and a group treated with the 3D-printed PCL–ADM NGCs. Sciatic nerve regeneration was assessed at 4 and 12 weeks postoperatively using electrophysiological measurements, histological staining, and electron microscopy. The PCL–ADM NGC demonstrated comparable axonal regeneration and functional recovery to autologous grafting, and it significantly outperformed silicone tubes in terms of axonal count and maximal electrophysiological response. Histological and ultrastructural analyses further confirmed that the PCL–ADM NGC facilitated organized regeneration with dense myelinated axons and reduced degenerative changes. The fabricated NGCs exhibited excellent flexibility without compromising lumen diameter, which is critical for adapting to the physiological environment of peripheral nerves. These findings indicate that combining synthetic polymers with biologically derived matrices can enhance the regenerative microenvironment and overcome limitations of traditional synthetic conduits. In conclusion, the 3D-printed PCL–ADM NGC represents a promising alternative to both silicone tube repair and autologous nerve grafting by providing structural support and bioactivity while reducing the need for donor nerve harvesting. Further studies in larger animal models and longer follow-up periods will be required to confirm long-term efficacy and support clinical translation of this technology. Full article

The growth and development of aquaculture organisms are significantly influenced by environmental variations shaped by different aquaculture systems. In this study, a 90-day controlled experiment was conducted to compare two pond culture setups for largemouth bass: with water hyacinth co-planted (FM group) and without (M group). As this experiment progressed, the FM group exhibited significantly superior water quality (p < 0.05) compared to the M group across multiple parameters, including total nitrogen (TN), total phosphorus (TP), ammonia nitrogen (NH₃-N), dissolved oxygen (DO) and transparency, among which, the difference in transparency was especially evident (p < 0.001). Subsequently, by 90 days, the fish body weight, condition factor, and gonadosomatic index (GSI) were significantly higher in the FM group than in the M group, with the GSI difference being particularly pronounced (p < 0.001). While the GSI of M group fishes ranged exclusively from 0.01 to 0.02 (M1), the FM group displayed a much-expanded GSI range of 0.01–0.06, with 21.4% at 0.01–0.02 (FM1), 48.1% at 0.02–0.03 (FM2), and 30.5% at 0.03–0.06 (FM3). Accordingly, omics analyses of ovarian tissues were conducted between the control (M1) and the high-performing groups (FM2 and FM3). The analyses identified significant enrichment of the glycerophospholipid metabolic pathway and a marked upregulation of the Mettl3 gene (log2FC = 12.59) in the FM2 and FM3 than the M1 group, and both the pathway and the Mettl3 gene were actively involved in growth, reproductive processes, and oocyte maturation. Given that water transparency was the most markedly improved parameter, our results indicate that it may be a key driver in upregulating ovarian glycerophospholipid metabolism and Mettl3 expression in largemouth bass, thereby promoting better growth and ovarian development. Full article

Yaks are important for the ecology and economy of the Qinghai-Tibetan Plateau. The growth of the yak industry depends on sustainable and accelerated growth of calves, sustaining herd reproduction and production systems. Yak calves born in the summer months of June and July are faced with a heightened risk of winter mortality. Exclusive traditional, natural feeding prolongs the suckling period, and this leads to a series of problems due to the harsh high-altitude environment, such as inadequate nutrition leading to retarded growth and an imbalanced herd structure. To enhance growth performance and breeding efficiency, 12 male calves of similar weights (68.53 ± 6.41 kg) were randomly assigned to a control group (suckle the dam (SU)) or an experimental group (early weaning with full feeding, concentrate and oat hay at a 7:3 ratio (CO)). The results showed that compared with suckling, early weaning with full feeding significantly improved the growth performance, volatile fatty acids and digestive enzyme activity. The abundance of the Firmicutes was reduced, but there was an increased abundance of Bacteroidetes, which affected the rumen metabolome. In conclusion, early weaning with full feeding improves growth performance, promotes rumen fermentation and carbohydrate degradation, reduces the diversity and richness of rumen microbial flora and alters the content and pathways of metabolites in yak calves. These factors contribute to the growth and market readiness of yak calves born in June and July, accelerate herd turnover and enhance the production efficiency of grazing yaks. Full article

Poly(ethylene glycol) (PEG) and poly(2-hydroxy ethyl methacrylate) are polymers used for many biomedical applications due to their biocompatibility, non-toxicity, and antibiofouling properties. In this work, a new comb-like hydrogel based on 2-hydroxyethyl methacrylate (HEMA) grafted onto a polyethylene glycol network (net-PEG) was synthesized by gamma radiation from Co⁶⁰ in two steps. First, PEG (Mw = 20,000) was crosslinked at 30 kGy, and then HEMA was grafted, varying the concentration (5–20% v/v) and irradiation dose (2.5–15 kGy). Results of infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) confirmed the incorporation of HEMA onto net-PEG. Moreover, the properties of comb-like hydrogel (net-PEG)-g-HEMA were studied through swelling kinetics, drug loading and release, antimicrobial activity, and biocompatibility assays. The findings showed a different behavior in swelling kinetics and drug delivery depending on HEMA grafting. Comb-like hydrogel with 30 and 66% grafting could load more ciprofloxacin (2 mg g⁻¹) than net-PEG (1.5 mg g⁻¹) but only release 38 and 48% at 24 h, respectively. In addition, all drug-loaded hydrogels displayed inhibition for Gram-negative bacteria (E. coli) and a cell viability superior of 95% using mouse embryonic fibroblasts (BALT/T3). Comb-like hydrogel has potential application in the biomedical field such as in wound dressings or controlled drug delivery systems. Full article

Background: Rhythmic sensory stimulation, including structured musical interventions, has gained renewed interest as a non-pharmacological strategy that may modulate cortical excitability and network stability in focal epilepsy. Although several small studies have reported changes in seizure frequency or epileptiform activity during rhythmic or music exposure, the underlying mechanisms and translational relevance remain insufficiently synthesized. Objective: This narrative review summarizes clinical evidence on music-based and rhythmic sensory interventions in focal epilepsy, outlines plausible neurophysiological mechanisms related to neural entrainment and large-scale network regulation, and discusses emerging opportunities for digital delivery of rhythmic protocols in everyday self-management. Methods: A structured search of recent clinical, neurophysiological, and rehabilitation literature was performed with emphasis on rhythmic auditory, tactile, and multimodal stimulation in epilepsy or related conditions. Additional theoretical and translational sources addressing oscillatory dynamics, entrainment, timing networks, and patient-centered digital tools were reviewed to establish a mechanistic framework. Results: Existing studies—although limited by small cohorts and heterogeneous methodology—suggest that certain rhythmic structures, including specific musical compositions, may transiently modulate cortical synchronization, reduce epileptiform discharges, or alleviate seizure-related symptoms in selected patients. Evidence from neurologic music therapy and rhythmic stimulation in other neurological disorders further supports the concept that externally delivered rhythms can influence timing networks, attentional control, and interhemispheric coordination. Advances in mobile health platforms enable structured rhythmic exercises to be delivered and monitored in real-world settings. Conclusions: Music-based and rhythmic sensory interventions represent a promising but underexplored adjunctive approach for focal epilepsy. Their effectiveness likely depends on individual network characteristics and on the structure of the applied rhythm. Digital integration may enhance personalization and adherence. Rigorous clinical trials and mechanistic studies are required to define optimal parameters, identify responders, and clarify the role of rhythmic stimulation within modern epilepsy care. Full article

Active screen plasma nitriding (ASPN) of additively manufactured nickel-based superalloys represents an understudied surface enhancement pathway. This study presents the first systematic investigation of ASPN applied to additively manufactured Inconel 939 (IN 939), evaluating four distinct post-processing routes combining heat treatment atmospheres (argon versus air cooling), vibratory finishing, and lapping under identical nitriding parameters (450 °C, 8 h, 25% N₂ + 75% H₂, 3 hPa). Contrasting nitriding behaviours emerged as a function of the post-processing route: the air-cooled thermal treatment (HT-air-vibr-lap) promotes formation of a thick Al/Cr-rich oxide layer (10–15 µm) that substantially inhibits nitrogen diffusion, resulting in thin and discontinuous nitrided layers. Conversely, the inert atmosphere route (HT-Ar-vibr-lap) circumvents oxide formation, enabling continuous S-phase (expanded austenite, γN) layer development of a 6.4 ± 0.3 µm thickness with exceptional surface hardness (~1200 HV, representing 3–4× enhancement relative to base material). X-ray diffraction confirmed S-phase formation with refined lattice parameter (3.609 Å) and secondary nitride phases (CrN-type and NbN/TaN-type precipitates). The post-processing sequence—particularly heat treatment atmosphere and mechanical finishing methodology—emerged as a critical controlling parameter for S-phase formation efficiency and mechanical properties of nitrided layers in additively manufactured nickel-based superalloys. This work addresses a knowledge gap distinct from the existing literature on conventional Inconel systems, establishing that controlled surface modification through post-processing can achieve the required properties. Full article

Background: Effective prevention of jellyfish stings is crucial for human safety during marine activities. Traditional protective methods are often limited in terms of coverage area and duration of protection; Methods: This study designed and tested a novel jellyfish-repellent textile by coating waterproof polyester fabric with copper ion-loaded multicompartmental nanoparticles, which repel jellyfish by disrupting their cellular membranes and physiological functions. The nanoparticles were synthesized to enable spatial separation of components, enhance stability, and allow controlled copper ion release. They were applied to the fabric in one step via high-voltage electrostatic spray technology, followed by characterization using SEM and FT-IR. The copper sulfate release profile and nanoparticle adhesion were analyzed. Jellyfish-repellent efficacy was evaluated, along with biocompatibility tests including skin sensitization (Magnusson and Kligman method), skin irritation (Draize test), and cytotoxicity (MTT assay on L929 cells and human dermal fibroblasts). Results: SEM confirmed the formation of uniform multicompartmental nanoparticles with sizes ranging from 2.28 to 3.15 μm. FT-IR verified successful anchoring of Cu²⁺ ions to fabric fibers through coordination with hydroxyl groups. Drug release tests demonstrated water-triggered controlled release of copper ions lasting over 168 h, with nanoparticle retention rates exceeding 70% on all fabrics. The textile showed significant effectiveness in repelling jellyfish. Moreover, no apparent sensitization, irritation, or cytotoxicity was observed. Conclusions: A novel jellyfish-repellent textile was successfully developed using copper ion-loaded multicompartmental nanoparticles. This textile provides a promising solution for preventing jellyfish stings and contributes to the advancement of protective gear for marine activities. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become highly prevalent worldwide, and its pathogenesis and progression mechanisms remain incompletely understood. An increased activation of innate immune cells in the liver contributes to hepatic fibrogenesis via a chronic loop of inflammation and regeneration processes. Among them are mast cells (MCs), whose role in hepatic cirrhosis secondary to MASLD remains poorly studied. Our aim was to evaluate differences in MC density in cirrhotic liver tissue among patients with MASLD and other chronic liver disease etiologies. For this, a retrospective study of MC count was performed in cirrhotic liver explants obtained from MASLD, alcohol-related liver disease (ALD), and autoimmune hepatitis (AIH). We included a control group of subjects without liver damage. Tryptase-positive MCs were identified by indirect immunofluorescence and quantified as MC density per low-power field (MC/LPF). Group differences were analyzed using the Kruskal–Wallis test with Dunn’s multiple comparisons, considering p < 0.05 as statistically significant. A significantly higher MC density was observed in MASLD, ALD, and AIH patients compared with the control group. The group analysis showed that ALD patients exhibited higher MC density than AIH, with no observed difference between ALD and MASLD. MC density was correlated positively with tobacco smoking and alcohol use in the full analyzed group, suggesting them as risk factors of high MC liver infiltration. We conclude that MC density is augmented in MASLD-related cirrhosis, highlighting potential links between lifestyle factors and MC-mediated hepatic inflammation. Future studies should explore the mechanisms driving this association and evaluate whether targeting MCs could help mitigate fibrosis progression. Full article