Search Results (14,400)

Schizochytrium is often added to feed to enhance the growth and health of farmed animals, yet research on its effects on amphibians remains relatively scarce. Here, this study investigated the effects of dietary Schizochytrium meal on growth, metamorphosis, intermediate metabolism, and intestinal health of bullfrogs. Six compound feeds (S0–S5) containing different gradients of Schizochytrium meal (0.00, 2.00, 5.00, 10.00, 15.00, and 20.00 g/kg diets) were formulated. After 90 days, the S4 group (15.00 g/kg) exhibited significantly superior growth performance, with the weight gain rate (WGR) increasing by up to 23.78% compared to the control (S0). Metamorphosis rate (MR) peaked at 23.33% in the S4 group. The enzyme activities of digestion (amylase (AMS), lipase (LPS), protease), brush border membrane (Na⁺, K⁺-ATPase, alkaline phosphatase (AKP), γ-glutamyl transferase (γ-GT), creatine kinase (CK), and antioxidation (superoxide dismutase (SOD), catalase (CAT)), as well as microvilli length and mucosal epithelial cell height in the intestine were the highest in the S4 group. Intestinal microbial diversity (Ace index) significantly increased by 41.28% in the S4 group, which also promoted beneficial bacteria. Key genes related to the GH-IGF-1 axis, metabolism, and intestinal barrier function were significantly upregulated with increasing Schizochytrium levels up to 15.00 g/kg, whereas pro-inflammatory genes showed an opposite trend. Overall, dietary supplementation with Schizochytrium meal at 15.00 g/kg promotes growth, metamorphosis, and intestinal health in bullfrog tadpoles by modulating the GH-IGF-1 axis, enhancing digestion and absorption, and improving intestinal integrity. Optimal Schizochytrium meal levels were identified as 13.27 g/kg. Full article

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Alterations in fibroblast growth factor receptor 2 (FGFR2), although rare, are emerging as important contributors to tumor progression and drug resistance. This review evaluates the molecular mechanisms, expression profiles, detection methods, and therapeutic implications of FGFR2 in GIST. Methods: We searched PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for studies published between January 2010 and June 2025, using combinations of keywords related to FGFR2, gastrointestinal stromal tumor, resistance mechanisms, gene fusion, amplification, polymorphisms, and targeted therapy. Eligible studies were critically assessed to distinguish GIST-specific data from evidence extrapolated from other cancers. Results:FGFR2 is expressed in multiple normal tissues and at variable levels in mesenchymal-derived tumors, including GIST. Its alterations occur in approximately 1–2% of GIST cases, most commonly as gene fusions (e.g., FGFR2::TACC2, <1%) or amplifications (1–2%); point mutations and clinically significant polymorphisms are extremely rare. These alterations activate the MAPK/ERK and PI3K/AKT pathways, contribute to bypass signaling, and enhance DNA damage repair, thereby promoting TKI resistance. Beyond mutations, mechanisms such as amplification, ligand overexpression, and microenvironmental interactions also play roles. FGFR2 alterations appear mutually exclusive with KIT/PDGFRA mutations but occasional co-occurrence has been reported. Current clinical evidence is largely limited to small cohorts, basket trials, or case reports. Conclusions:FGFR2 is an emerging oncogenic driver and biomarker of resistance in a rare subset of GISTs. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target. Full article

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC. Full article

Treatment for acute liver failure (ALF) is constrained by shortages of liver transplant donors and immune rejection. Porcine bone marrow mesenchymal stem cells (pBMSCs) demonstrate clinical potential in xenotransplantation due to their abundant availability, low immunogenicity, and strong proliferative activity. This study is the first to investigate the reparative effects and mechanisms of pBMSCs derived from Luopan Mountain pigs in a D-galactosamine (D-GalN)-induced ALF rat model. The results demonstrated that tail-vein transplantation of pBMSCs significantly improved survival rates in ALF rats; reduced serum ALT, AST, and TBIL levels; enhanced hepatic glycogen metabolism; and mitigated histopathological liver damage. Additionally, pBMSC transplantation upregulated serum HGF, IGF-1, and VEGF levels while inhibiting hepatocyte apoptosis. Mechanistic studies indicate that pBMSCs promote liver function recovery and regeneration by activating the PI3K/Akt/mTOR signaling pathway and suppressing its key negative regulator, PTEN, by regulating the expression of key genes involved in inflammation, fibrosis, proliferation, and apoptosis. This study provides crucial experimental evidence for the use of pBMSCs in treating acute liver failure (ALF) and lays the groundwork for its clinical translation in the field of xenotransplantation. Full article

Graduate students often experience difficulties in learning statistics, particularly those who have limited mathematical backgrounds. In recent years, Learning Management Systems (LMS) and Problem-Based Learning (PBL) have been widely adopted to support instruction, yet little research has explored how these tools relate to learning outcomes using mixed methods design. Limited studies have employed machine learning methods such as clustering analysis in Learning Analytics (LA) to explore different behavior of clusters based on students log data. This study followed an explanatory sequential mixed methods design to examine student engagement patterns on Canvas and learning outcomes of students in a graduate-level statistics course. LMS log data and surveys were collected from 31 students, followed by interviews with 19 participants. K-means clustering revealed two groups: a high-performing group with lower LMS engagement and a low-performing group with higher LMS engagement. Six themes emerged from a thematic analysis of interview transcripts: behavioral differences in engagement, the role of assessment, emotional struggle, self-efficacy, knowledge or skill gain, and structured instructional support. Results indicated that low-performing students engaged more frequently and benefited from structured guidance and repeated exposure. High-performing students showed more proactive and consistent engagement habits. These findings highlight the importance of intentional course design that combines PBL with LMS features to support diverse learners. Full article

Lead (Pb) in soil poses serious environmental and health risks, and its removal requires complex and costly treatment methods to meet strict regulatory standards. To effectively address this challenge, innovative and efficient techniques are essential. Sepiolite-supported MnFe₂O₄ (MnFe₂O₄/SEP) composites were synthesized via a chemical co-precipitation method. The effects of MnFe₂O₄/SEP on soil pH, cation exchange capacity (CEC), available Pb content, Pb²⁺ uptake, and the activities of antioxidant enzymes in Brassica chinensis (Pak Choi) were examined. MnFe₂O₄/SEP showed superior Pb²⁺ adsorption compared to SEP alone, fitting Langmuir models, Dubinin-Radushkevich (D-R) models, Temkin models and pseudo-second-order kinetics. The maximum adsorption capacities at 298, 308, and 318 K were 459, 500 and 549 mg·g⁻¹, respectively. XPS analysis indicated that chemisorption achieved through ion exchange between Pb²⁺ and H⁺ was the main mechanism. MnFe₂O₄/SEP increased the soil pH by 0.2–1.5 units and CEC by 18–47%, while reducing available Pb by 12–83%. After treatment with MnFe₂O₄/SEP, acid-extractable and reducible Pb in the soil decreased by 14% and 39%, while oxidizable and residual Pb increased by 26% and 21%, respectively. In Brassica chinensis, MnFe₂O₄/SEP reduced Pb²⁺ uptake by 76%, increased chlorophyll content by 36%, and decreased malondialdehyde (MDA) levels by 36%. The activities of antioxidant enzymes—superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)—were decreased by 29%, 38% and 17%, respectively. These findings demonstrate that MnFe₂O₄/SEP is an efficient Pb²⁺ adsorbent that immobilizes Pb in soil mainly through ion exchange, thereby providing a highly effective strategy for remediating Pb-contaminated soils and improving plant health. Full article

The study evaluates the impact of massive electric vehicle (EV) penetration on Quito’s 138 kV distribution system in Ecuador, employing a probabilistic approach to support a sustainable energy transition. The rapid adoption of EVs, as projected by Ecuador’s National Electromobility Strategy, poses significant challenges to the capacity and reliability of the city’s electrical infrastructure. The objective is to analyze the system’s response to increased EV load and assess its readiness for this scenario. A methodology integrating dynamic battery modeling, Monte Carlo simulations, and power flow analysis was employed, evaluating two penetration levels: 800 and 25,000 EVs, under homogeneous and non-homogeneous distribution scenarios. The results indicate that while the system can handle moderate penetration, high penetration levels lead to overloads in critical lines, such as L10–15 and L11–5, compromising normal system operation. It is concluded that specific infrastructure upgrades and the implementation of smart charging strategies are necessary to mitigate operational risks. This approach provides a robust framework for effective planning of EV integration into the system, contributing key insights for a transition toward sustainable mobility. Full article

Road-surface distress poses a serious threat to traffic safety and imposes a growing burden on urban maintenance budgets. While modern detectors based on convolutional networks and Vision Transformers achieve strong frame-level performance, they often overlook an essential property of road environments—structural symmetry within road networks and damage patterns. We present Graph-MambaRoadDet (GMRD), a symmetry-aware and lightweight framework that integrates dynamic graph reasoning with state–space modeling for accurate, topology-informed, and real-time road damage detection. Specifically, GMRD employs an EfficientViM-T1 backbone and two DefMamba blocks, whose deformable scanning paths capture sub-pixel crack patterns while preserving geometric symmetry. A superpixel-based graph is constructed by projecting image regions onto OpenStreetMap road segments, encoding both spatial structure and symmetric topological layout. We introduce a Graph-Generating State–Space Model (GG-SSM) that synthesizes sparse sample-specific adjacency in $\mathcal{O}\left(M\right)$ time, further refined by a fusion module that combines detector self-attention with prior symmetry constraints. A consistency loss promotes smooth predictions across symmetric or adjacent segments. The full INT8 model contains only 1.8 M parameters and 1.5 GFLOPs, sustaining 45 FPS at 7 W on a Jetson Orin Nano—eight times lighter and 1.7× faster than YOLOv8-s. On RDD2022, TD-RD, and RoadBench-100K, GMRD surpasses strong baselines by up to +6.1 mAP_50:95 and, on the new RoadGraph-RDD benchmark, achieves +5.3 G-mAP and +0.05 consistency gain. Qualitative results demonstrate robustness under shadows, reflections, back-lighting, and occlusion. By explicitly modeling spatial and topological symmetry, GMRD offers a principled solution for city-scale road infrastructure monitoring under real-time and edge-computing constraints. Full article

Directive (EU) 2024/3019 on urban wastewater treatment requires municipal wastewater treatment plants (WWTPs) to achieve energy neutrality by 2045. This study assessed the energy efficiency of a WWTP in central Poland over eight years (2015–2022), considering influent variability, electricity use and cost, and biogas recovery. The facility served 41,951–44,506 inhabitants, with treated wastewater volumes of 3.08–3.93 million m³/year and a real population equivalent (PE) of 86,602–220,459. Over the study period, the specific energy demand remained stable at 0.92–1.20 kWh/m³ (average 1.04 ± 0.09 kWh/m³), equivalent to 17.4–36.3 kWh/PE∙year. Energy efficiency indicators (EEIs) per pollutant load removed averaged 1.12 ± 0.28 kWh/kgBODrem, 0.53 ± 0.12 kWh/kgCODrem, 1.18 ± 0.36 kWh/kgTSSrem, 12.1 ± 1.5 kWh/kgTNrem, and 62.3 ± 11.7 kWh/kgTPrem. EEI per cubic meter of treated wastewater proved to be the most reliable metric for predicting energy demand under variable influent conditions. Electricity costs represented 4.48–13.92% of the total treatment costs, whereas co-generation from sludge-derived biogas covered 18.1–68.4% (average 40.8 ± 13.8%) of the total electricity demand. Recommended pathways to energy neutrality include co-digestion with external substrates, improving anaerobic digestion efficiency, integrating photovoltaics, and optimizing electricity use. Despite fluctuations in influent quality and load, the ultimate effluent quality consistently complied with legal requirements, except for isolated cases of exceeded phosphorus levels. Full article

The systematic economic development of European Union member states has resulted in a dynamic increase in road transport, accompanied by adverse environmental impacts. Consequently, research efforts have focused on identifying technical solutions to reduce fuel and/or energy consumption. One promising approach involves the formation of homogeneous and heterogeneous vehicle platoons. This study presents the results of numerical simulations and analyses of aerodynamic and aeroacoustic phenomena generated by heterogeneous vehicle platoons composed of passenger cars, delivery vans, and trucks. A total of 54 numerical models were developed in various configurations, considering three vehicle speeds and three inter-vehicle distances. The analysis was conducted using Computational Fluid Dynamics (CFD) methods with the following two turbulence models: the k–ω Shear Stress Transport (SST) model and Large Eddy Simulation (LES), combined with the Ffowcs Williams–Hawkings acoustic analogy to determine sound pressure levels. Verification calculations were performed using methods dedicated to environmental noise analysis, supplemented by acoustic field measurements. The results conclusively demonstrate that vehicle movement in specific platoon configurations can lead to significant fuel and/or energy savings, as well as reductions in harmful emissions. This solution may be implemented in the future as an integral component of Intelligent Transportation Systems (ITSs) and Intelligent Environmental Management Systems (IEMSs). Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major causes of morbidity and mortality, yet no targeted pharmacological therapy is available. Excessive neutrophil and macrophage infiltration drives reactive oxygen species (ROS) production and cytokine release, leading to alveolar–capillary barrier disruption and fatal respiratory failure. Methods: We applied an integrative multi-omics strategy combining single-cell transcriptomics, peripheral blood proteomics, and lung tissue proteomics in a lipopolysaccharide (LPS, 10 mg/kg)-induced mouse ALI model to identify key signaling pathways. Harpagide, an iridoid glycoside identified from our natural compound screen, was evaluated in vivo (40 and 80 mg/kg) and in vitro (0.1–1 mg/mL). Histopathology, oxidative stress markers (SOD, GSH, and MDA), cytokine levels (IL-6 and IL-1β), and signaling proteins (HIF-1α, p-PI3K, p-AKT, Nrf2, and HO-1) were quantitatively assessed. Direct target engagement was probed using surface plasmon resonance (SPR), the cellular thermal shift assay (CETSA), and 100 ns molecular dynamics (MD) simulations. Results: Multi-omics profiling revealed robust activation of HIF-1, PI3K/AKT, and glutathione-metabolism pathways following the LPS challenge, with HIF-1α, VEGFA, and AKT as core regulators. Harpagide treatment significantly reduced lung injury scores by ~45% (p < 0.01), collagen deposition by ~50%, and ROS accumulation by >60% relative to LPS (n = 6). The pro-inflammatory cytokines IL-6 and IL-1β were reduced by 55–70% at the protein level (p < 0.01). Harpagide dose-dependently suppressed HIF-1α and p-AKT expression while enhancing Nrf2 and HO-1 levels (p < 0.05). SPR confirmed direct binding of Harpagide to HIF-1α (KD = 8.73 µM), and the CETSA demonstrated enhanced thermal stability of HIF-1α. MD simulations revealed a stable binding conformation within the inhibitory/C-TAD region after 50 ns. Conclusions: This study reveals convergent immune–microenvironmental regulatory mechanisms across cellular and tissue levels in ALI and demonstrates the protective effects of Harpagide through multi-pathway modulation. These findings offer new insights into the pathogenesis of ALI and support the development of “one-drug, multilayer co-regulation” strategies for systemic inflammatory diseases. Full article

Ensuring thermal stability is a major concern in lithium-ion battery systems. Although phase change materials (PCMs) provide a passive approach for temperature regulation, they are limited by poor heat conduction and potential leakage during phase transitions. This study develops a novel composite PCM (CPCM) using paraffin (PA) as the matrix, copper foam (CF) as a conductive skeleton (10–30 pores per inch, PPI), and a low-melting-point alloy (LMA) as an encapsulant to prevent leakage. The effects of CF pore size on thermal conductivity, impregnation ratio, and leakage resistance were systematically investigated. Results show that CPCM with 10 PPI CF achieved the highest thermal conductivity (4.42 W·m⁻¹·K⁻¹), while LMA encapsulation effectively eliminated leakage. The thermal management performance was evaluated on both a single 18,650 LIB cell and a 2S2P module during rate discharging at 1C, 2C, and 3C. For the module at 3C, the 10 PPI CPCM significantly lowered the maximum temperature from 75.9 °C to 44.6 °C and critically reduced the maximum temperature difference between cells from 10.2 °C to a safe level of 1.2 °C, significantly improving temperature uniformity. This work provides a high-conductivity and leakage-proof CPCM solution based on LMA-encapsulated CF/PA for enhanced thermal safety and uniformity in LIB modules. Full article

Background: Hypophosphatemia is a frequently underestimated metabolic disorder, yet it can be one of the first biochemical findings in primary hyperparathyroidism (PHPT). Current diagnostic and surgical criteria for PHPT do not include serum phosphate, despite its potential value as an early marker. Methods: We report the case of a 79-year-old woman with type 2 diabetes mellitus, hypertension and osteoarthritis, followed since 2015 for persistent hypophosphatemia (0.8 mg/dL) and stress fractures. Results: Initial calcium and vitamin D levels were normal, but PTH was elevated. Bone scintigraphy revealed multiple stress fractures, while ultrasound and sestamibi scan were inconclusive. Despite cholecalciferol and calcitriol supplementation, hypophosphatemia persisted. From 2023, progressive hypercalcemia developed (10.9 mg/dL), with sustained hypophosphatemia (1.7 mg/dL), persistently high PTH (121 pg/mL) and markedly elevated FGF-23 (1694 kRU/L). Renal phosphate wasting was demonstrated, with reduced tubular reabsorption. An 18F-fluorocholine PET-CT performed in 2024 identified two right parathyroid adenomas, establishing the diagnosis of PHPT. The patient was referred for parathyroidectomy. Conclusions: Hypophosphatemia may serve as a complementary biomarker in the diagnostic and therapeutic approach to PHPT, but only after other potential causes of low phosphate levels have been excluded, as illustrated in this case. Its consideration could facilitate the early identification of PHPT and improve clinical decision-making, particularly in patients who do not meet classical surgical indications. Full article

Background and Clinical Significance: In hepatocellular carcinoma (HCC), numerous signaling pathways become aberrantly regulated, resulting in sustained cellular proliferation and enhanced metastatic potential. Tumors that lack PYGO2 may not show the same types of tissue remodeling or regenerative features driven by the Wnt/β-catenin pathway, which could make the tumor behave differently from others that are Wnt-positive. PIK3CA-positive tumors are often associated with worse prognosis due to the aggressive nature of the PI3K/AKT pathway activation. This is linked to higher chances of metastasis, recurrence, and resistance to therapies that do not target this pathway. Case presentation: In this paper we present a rare case of hepatocellular carcinoma with PIK3CA-positive and PYGO2-negative signaling pathways, several key aspects of the tumor’s behavior, prognosis, and treatment options. Although alpha-fetoprotein (AFP) levels were significantly elevated, the CT and MRI examination showed characteristics of malignancy, HCC with secondary hepatic lesions and associated perfusion disturbances. The case particularities and immunohistochemistry features are highlighted in the context of literature review, the PIK3CA mutation suggesting the activation of the PI3K/AKT/mTOR pathway, a critical signaling pathway involved in cell survival, proliferation, and metabolism. Conclusions: Due to the aggressive nature of PIK3CA mutations, close monitoring and consideration of immunotherapy and targeted treatments are of crucial importance. Full article

Magnetocardiography (MCG) offers a noninvasive method for early screening and precise localization of cardiovascular diseases by measuring picotesla-level weak magnetic fields induced by cardiac electrical activity. However, in unshielded magnetic environments, geomagnetic disturbances, power-frequency electromagnetic interference, and physiological/motion artifacts can significantly overwhelm effective magnetocardiographic components. To address this challenge, this paper systematically constructs an integrated denoising framework, termed “AOA-VMD-WT”. In this approach, the Arithmetic Optimization Algorithm (AOA) adaptively optimizes the key parameters (decomposition level K and penalty factor α) of Variational Mode Decomposition (VMD). The decomposed components are then regularized based on their modal center frequencies: components with frequencies ≥50 Hz are directly suppressed; those with frequencies <50 Hz undergo wavelet threshold (WT) denoising; and those with frequencies <0.5 Hz undergo baseline correction. The purified signal is subsequently reconstructed. For quantitative evaluation, we designed performance indicators including QRS amplitude retention rate, high/low frequency suppression amount, and spectral entropy. Further comparisons are made with baseline methods such as FIR and wavelet soft/hard thresholds. Experimental results on multiple sets of measured MCG data demonstrate that the proposed method achieves an average improvement of approximately 8–15 dB in high-frequency suppression, 2–8 dB in low-frequency suppression, and a decrease in spectral entropy ranging from 0.1 to 0.6 without compromising QRS amplitude. Additionally, the parameter optimization exhibits high stability. These findings suggest that the proposed framework provides engineerable algorithmic support for stable MCG measurement in ordinary clinic scenarios. Full article