Search Results (450)

Metabolic dysfunction-associated steatotic liver disease (MASLD) begins with hepatic lipid accumulation and triggers insulin resistance. Hibiscus leaf extract exhibits antioxidant and anti-atherosclerotic activities, and is rich in (−)-epicatechin gallate (ECG). Despite ECG’s well-known pharmacological activities and its total antioxidant capacity being stronger than that of other catechins, its regulatory effects on MASLD have not been fully described previously. Therefore, this study attempted to evaluate the anti-MASLD potential of ECG isolated from Hibiscus leaves on abnormal lipid and glucose metabolism in hepatocytes. First, oleic acid (OA) was used as an experimental model to induce lipid dysmetabolism in human primary hepatocytes. Treatment with ECG can significantly (p < 0.05) reduce the OA-induced cellular lipid accumulation. Nile red staining revealed, compared to the OA group, the inhibition percentages of 29, 61, and 82% at the tested doses of ECG, respectively. The beneficial effects of ECG were associated with the downregulation of SREBPs/HMGCR and upregulation of PPARα/CPT1 through targeting AMPK. Also, ECG at 0.4 µM produced a significant (p < 0.01) decrease in oxidative stress by 83%, and a marked (p < 0.05) increase in glycogen synthesis by 145% on the OA-exposed hepatocytes with insulin signaling blockade. Mechanistic assays indicated lipid and glucose metabolic homeostasis of ECG might be mediated via regulation of lipogenesis, fatty acid β-oxidation, and insulin resistance, as confirmed by an AMPK inhibitor. These results suggest ECG is a dual modulator of lipid and carbohydrate dysmetabolism in hepatocytes. Full article

Fat embolism is a critical medical emergency often resulting from long bone fractures or amputations, leading to acute respiratory distress syndrome (ARDS). The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is activated by reactive oxygen species and tissue damage, contributing to inflammatory responses. This study examines the role of NLRP3 in fat embolism-induced ARDS and evaluates the therapeutic potential of MCC950, a selective NLRP3 antagonist. Fat embolism was induced by fatty micelle injection into the tail vein of Sprague Dawley rats. Pulmonary injury was assessed through lung weight gain as an edema indicator, NLRP3 expression via Western blot, and IL-1β levels using ELISA. Histological damage and macrophage infiltration were evaluated with hematoxylin and eosin staining. Fat embolism significantly increased pulmonary NLRP3 expression, lipid peroxidation, IL-1β release, and macrophage infiltration within four hours, accompanied by severe pulmonary edema. NLRP3 was localized in type I alveolar cells, co-localizing with aquaporin 5. Administration of MCC950 significantly reduced inflammatory responses, lipid peroxidation, pulmonary edema, and histological damage, while attenuating MAPK cascade phosphorylation of ERK and Raf. These findings suggest that NLRP3 plays a critical role in fat embolism-induced acute respiratory distress syndrome, and its inhibition by MCC950 may offer a promising therapeutic approach. Full article

Mixing enthalpy (ΔH_mix), mixing entropy (ΔS_mix), atomic-size difference (δ), and valence electron concentration (VEC) are the indicators determining the phase structures of multi-principal element alloys. Exploring the relationships between the structures and properties of multi-principal element films is a fundamental study. TiZrHf films with a ΔH_mix of 0.00 kJ/mol, ΔS_mix of 9.11 J/mol·K (1.10R), δ of 3.79%, and VEC of 4.00 formed a hexagonal close-packed (HCP) solid solution. Exploring the characterization of TiZrHf films after solving Ta, Y, and Cr atoms with distinct atomic radii is crucial for realizing multi-principal element alloys. This study fabricated TiZrHf, TiZrHfTa, TiZrHfY, and TiZrHfCr films through co-sputtering. The results indicated that TiZrHfTa films formed a single body-centered cubic (BCC) solid solution. In contrast, TiZrHfY films formed a single HCP solid solution, and TiZrHfCr films formed a nanocrystalline BCC solid solution. The crystallization of TiZrHf(Ta, Y, Cr) films and the four indicators mentioned above for multi-principal element alloy structures were correlated. The mechanical properties and thermal stability of the TiZrHf(Ta, Y, Cr) films were investigated. Full article

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. It is characterized by mitochondrial dysfunction, increased reactive oxygen species (ROS), α-synuclein (α-syn) and phosphorylated-tau protein (p-tau) aggregation, and dopaminergic neuron cell death. Current drug therapies only provide temporary symptomatic relief and fail to stop or reverse disease progression due to the severe side effects or the blood–brain barrier. This study aimed to investigate the neuroprotective effects of an intermittent heating approach, thermal cycling-hyperthermia (TC-HT), in an in vitro PD model using rotenone (ROT)-induced human neural SH-SY5Y cells. Our results revealed that TC-HT pretreatment conferred neuroprotective effects in the ROT-induced in vitro PD model using human SH-SY5Y neuronal cells, including reducing ROT-induced mitochondrial apoptosis and ROS accumulation in SH-SY5Y cells. In addition, TC-HT also inhibited the expression of α-syn and p-tau through heat-activated pathways associated with sirtuin 1 (SIRT1) and heat-shock protein 70 (Hsp70), involved in protein chaperoning, and resulted in the phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β), which inhibit p-tau formation. These findings underscore the potential of TC-HT as an effective treatment for PD in vitro, supporting its further investigation in in vivo models with focused ultrasound (FUS) as a feasible heat-delivery approach. Full article

In this study, we developed a game related to Palaeoloxodon huaihoensis to enhance public interest in learning about its ecology. The game integrates education and entertainment elements at four interactive levels “See Sea Bones,” “Assembling Organs,” “Bacterias Cleaner,” and “Painting Elephant” to allow players to explore the fossil structure, internal organs, and historical background of Palaeoloxodon huaihoensis. In the design process, we incorporated the design–play–experience framework and the gameplay–purpose–scope (GPS) model to balance entertainment and education. To evaluate the effectiveness of the developed game, a questionnaire survey on a Likert scale was conducted with 180 participants visiting the National Museum of Natural Science, Taiwan. The results indicated that the majority of the players were satisfied with the game’s design and content, particularly in terms of its ability to stimulate creativity. This research demonstrated the potential of games in museum education and provides insights for future optimization. Full article

This study establishes a standardized geometric model of the tibiotalar joint based on anatomical morphology and validates its statistical representativeness. Using this model, a novel fusion implant was developed and evaluated for its biomechanical performance through nonlinear finite element (FE) analysis compared to traditional fixation methods. A morphological database of the tibiotalar joint was built using 30 computed tomography (CT) scans to determine key dimensional parameters, and a novel fusion implant was designed to match the joint’s natural curvature. FE analysis compared three fixation strategies: (1) the novel implant with an anterior plate, (2) the anterior plate alone, and (3) three compression screws. Biomechanical parameters, including joint contact area, micromotion, and stress distribution, were analyzed under simulated loading conditions. The novel implant achieved the highest joint contact area (95.0%) and lowest tibial micromotion (0.033 mm), significantly reducing stress concentration compared to anterior plate fixation (49.8% contact; 0.068 mm micromotion) and compression screws (78.2% contact; 0.355 mm micromotion). Constructing a standardized tibiotalar joint model with verified normal distribution is crucial for ensuring broad implant applicability. FE analysis demonstrated that the novel implant enhances joint contact, reduces micromotion, and optimizes stress distribution, offering a promising approach for improving surgical outcomes in tibiotalar joint fusion. Full article

Background and Objectives: Spontaneous bacterial peritonitis (SBP) is both a prevalent and severe complication among individuals with cirrhosis. This systematic review and meta-analysis was designed to evaluate the diagnostic accuracy of procalcitonin (PCT) and compare it to C-reactive protein (CRP) in cirrhotic patients with suspected SBP. Materials and Methods: We performed an extensive literature review utilizing databases including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Original investigations reporting PCT diagnostic accuracy for SBP in cirrhotic populations were included. We computed pooled measures of sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and SROC curve area under the curve, with corresponding 95% confidence intervals (CIs). Results: Meta-analytical synthesis encompassed twenty eligible studies. Diagnostic accuracy analysis revealed PCT sensitivity of 0.73 (95% CI, 0.61–0.83) and specificity of 0.88 (95% CI, 0.83–0.91). Likelihood ratio yielded positive values of 6.0 (95% CI, 4.1–8.8) and negative values of 0.30 (95% CI, 0.20–0.47). Overall discriminative ability, quantified through SROC curve analysis, demonstrated an AUC of 0.90 (95% CI, 0.87–0.92). Head-to-head comparisons between PCT and CRP were available from ten studies, demonstrating PCT’s superior diagnostic accuracy over CRP, with significantly higher AUC values (PCT: 0.89, 95% CI 0.86–0.91; CRP: 0.74, 95% CI 0.70–0.78, p < 0.01). Conclusions: Although PCT demonstrates higher diagnostic accuracy than CRP, it does not appear to provide sufficient accuracy to support treatment decisions for SBP. We recommend not relying solely on the PCT test and advise that it be interpreted in conjunction with clinical findings. Full article

Data science has become an essential component in professional sports, particularly for predicting team performance and outcomes. This study aims to develop and evaluate machine learning models that accurately predict game outcomes in the Chinese Professional Baseball League (CPBL). Method: A total of 859 games from the 2021 to 2023 regular seasons were analyzed, using both traditional baseball statistics and advanced sabermetric indicators such as the Weighted Runs Created Plus (wRC+), Weighted Runs Above Average (wRAA), and Percentage of Leadoff Batters on Base (PLOB%). Five machine learning models—decision tree, logistic regression, Neural Network, Random Forest, and XGBoost—were constructed and assessed through a five-fold cross-validation. Evaluation metrics included accuracy, F1 scores, sensitivity, specificity, and the AUC-ROC. Results: Among the models, logistic regression and XGBoost achieved the highest performance, with an accuracy ranging from 0.89 to 0.93 and an AUC-ROC from 0.97 to 0.98. The feature importance and SHapley Additive exPlanations (SHAP) analysis revealed that the wRC+ and PLOB% were the most influential predictors, reflecting the offensive efficiency and pitching control. Conclusion: The results suggest that combining interpretable machine learning with sabermetrics provides valuable insights for coaches and analysts in professional baseball. Furthermore, incorporating performance weighting based on game context may further enhance model accuracy. This research demonstrates the potential of data-driven strategies in sports analytics and decision-making. Full article

Background: Radiolabeled compounds can serve as diagnostic or therapeutic agents depending on the characteristics of the isotopes used. IMPY (6-iodo-2-(4′-dimethylamino)-phenyl-imidazo[1,2-a]pyridine) is a lipophilic derivative of thioflavin-T, designed to function as a tracer when labeled with radioactive iodine. While it has been primarily studied for imaging applications, its potential therapeutic effects when labeled with iodine-125 (¹²⁵I) remain to be explored. Methods: In this study, IMPY was synthesized and labeled with ¹²⁵I for therapeutic purposes. Three different labeling methods were employed: isotope exchange reaction, redox reaction, and the Iodogen technique. The radiochemical yield of each method was determined to identify the most effective approach. Additionally, the effects of ¹²⁵I-IMPY on neuroblastoma cells were evaluated by assessing its toxicity and cellular uptake. Results: The radiochemical yields for the isotope exchange reaction, redox reaction, and Iodogen technique were found to be 0.96%, 10.74%, and 96.52%, respectively. The Iodogen technique exhibited the highest yield, exceeding 90% even after 48 h, making it the most efficient method. Furthermore, the impact of ¹²⁵I-IMPY on neuroblastoma cells was analyzed, revealing significant cellular uptake and potential therapeutic effects. Conclusions: This study demonstrated that the Iodogen technique is the most effective method for labeling IMPY with ¹²⁵I. The high labeling efficiency and observed cellular effects suggest that ¹²⁵I-IMPY could be considered not only as a tracer but also as a potential therapeutic agent for neuroblastoma. Further studies are needed to explore its full therapeutic potential and mechanism of action. Full article

Hepatitis C virus (HCV) infection remains a significant global health burden, driven by the emergence of drug-resistant strains and the limited efficacy of current antiviral therapies. A promising strategy for therapeutic intervention involves targeting the NS3 protease, a viral enzyme essential for replication. In this study, we present the first computational model specifically designed to identify NS3 protease inhibitory peptides (NS3IPs). Using amino acid composition (AAC) and K-spaced amino acid pair composition (CKSAAP) features, we developed machine learning classifiers based on support vector machine (SVM) and random forest (RF), achieving accuracies of 98.85% and 97.83%, respectively, validated through 5-fold cross-validation and independent testing. To support the accessibility of the strategy, we implemented a web-based tool, iDNS3IP, which enables real-time prediction of NS3IPs. In addition, we performed feature space analyses using PCA, t-SNE, and LDA based on AAindex descriptors. The resulting visualizations showed a distinguishable clustering between NS3IPs and non-inhibitory peptides, suggesting that inhibitory activity may correlate with characteristic physicochemical patterns. This study provides a reliable and interpretable platform to assist in the discovery of therapeutic peptides and supports continued research into peptide-based antiviral strategies for drug-resistant HCV. To enhance its flexibility, the iDNS3IP web tool also incorporates a BLAST-based similarity search function, enabling users to evaluate inhibitory candidates from both predictive and homology-based perspectives. Full article

This study was conducted at SPINLab. The full-scale experiments were performed using two experimental spaces of identical specifications to investigate the effects of electrochromic film (OG + EC_ON or OG + EC_OFF) on indoor environment and air conditioning electricity consumption in buildings with different orientations (East and West). The electricity-saving effects are more pronounced on the building’s west-facing side than on its east-facing side. For the east-facing side, the average electricity savings for OG + EC_ON and OG + EC_OFF were 4.5%, and 5.1%, respectively. For the west-facing side, the average electricity savings increased to 9.2% and 9.4% for OG + EC_ON and OG + EC_OFF. The research results on thermal comfort indicate (PMV) that applying electrochromic film (OG + EC_ON or OG + EC_OFF) significantly improved indoor thermal comfort compared to using clear glass (OG) alone. The visual comfort analysis results indicate that the opaque (OG + EC_OFF) and transparent (OG + EC_ON) states of electrochromic film could reduce daylight glare probability (DGP) values. However, due to the light-scattering properties of the liquid crystal droplets, the OG + EC_OFF and OG + EC_ON states of the electrochromic film increased DGP values in 26.5% and 41.5% of the cases, respectively, when sunlight directly entered the interior. Full article

Background/Objectives: Chronic obstructive pulmonary disease (COPD) remains a leading cause of death worldwide, with emphysema progression providing valuable insights into disease development. Clinical assessment approaches, including pulmonary function tests and high-resolution computed tomography, are limited by accessibility constraints and radiation exposure. This study, therefore, proposed an alternative approach by integrating the novel biomarker long non-coding interleukin-7 receptor α-subunit gene (lnc-Il7R), along with other easily accessible clinical and biochemical metrics, into machine learning (ML) models. Methods: This cohort study collected baseline characteristics, COPD Assessment Test (CAT) scores, and biochemical details from the enrolled participants. Associations with emphysema severity, defined by a low attenuation area percentage (LAA%) threshold of 15%, were evaluated using simple and multivariate-adjusted models. The dataset was then split into training and validation (80%) and test (20%) subsets. Five ML models were employed, with the best-performing model being further analyzed for feature importance. Results: The majority of participants were elderly males. Compared to the LAA% <15% group, the LAA% ≥15% group demonstrated a significantly higher body mass index (BMI), poor pulmonary function, and lower expression levels of lnc-Il7R (all p < 0.01). Fold changes in lnc-IL7R were strongly and negatively associated with LAA% (p < 0.01). The random forest (RF) model achieved the highest accuracy and area under the receiver operating characteristic curve (AUROC) across datasets. A feature importance analysis identified lnc-IL7R fold changes as the strongest predictor for emphysema classification (LAA% ≥15%), followed by CAT scores and BMI. Conclusions: Machine learning models incorporated accessible clinical and biochemical markers, particularly the novel biomarker lnc-IL7R, achieving classification accuracy and AUROC exceeding 75% in emphysema assessments. These findings offer promising opportunities for improving emphysema classification and COPD management. Full article

Poria cocos extract attenuates MK-801-induced hyperactivity via RhoA/ROCK1 pathway modulation in mice. Background/Objectives: Poria cocos (P. cocos), a traditional East Asian medicinal mushroom, serves as a medicine and nutritional supplement, has been used to improve sleep and mood. Its bioactive compounds may regulate calcium signaling and Rho family proteins, which are linked to cytoskeletal remodeling and psychiatric symptoms. This study investigated the effects of P. cocos ethanol extract (PCEE) on Rho signaling, cytoskeleton dynamics, and behavior in MK-801-treated cells and mice. Methods: PCEE components were analyzed using HPLC. IMR-32 and Neuro2A cells were treated with MK-801 and PCEE to assess changes in F-actin (via fluorescence staining), cell migration (wound healing and Transwell assays), and Rho signaling proteins (by immunoblotting). In vivo, C57BL/6 mice received MK-801 to induce hyperactivity, followed by PCEE treatment. RhoA/ROCK1 pathway protein levels in the prefrontal cortex were analyzed. Results: PCEE reversed MK-801-induced inhibition of cell migration, F-actin disruption, and dysregulation of Rho-related proteins (RhoGDI1, RhoA, CDC42, Rac1, ROCK1, MLC2, PFN1). In mice, PCEE significantly reduced MK-801-induced hyperactivity and normalized RhoA/ROCK1 signaling in the brain. Conclusion: PCEE modulates cytoskeletal dynamics by regulating RhoA/ROCK1 signaling and attenuates MK-801-induced behavioral and molecular changes, suggesting its therapeutic potential for psychosis with fewer adverse effects. Full article

Background: The mutation rate of p53 in breast cancer is around 20%. Specific p53 mutations exhibit prion-like abnormal misfolding and aggregation and gain oncogenic function, causing resistance to the chemotherapy drug doxorubicin. In this study, we identified key upstream regulatory molecules that inhibit the aggregation of p53 with the aim of increasing the anticancer effect of doxorubicin. Methods: Thioflavin T was employed as a fluorescent probe to detect prion-like protein aggregates within cells, the response to various inhibitors was evaluated using CCK8 assay, and the coefficient of drug interaction was calculated. The cell apoptosis ratio was evaluated using Caspase-3/7 based flow cytometry assay. Results: MDA-MB-231 cells (with p53 R280K mutation) and T47D cells (with p53 L194F mutation) had a strong Thioflavin T staining signal, but MDA-MB-468 cells (with p53 R273H mutation) had a weak Thioflavin T signal. Compared to MDA-MB-468 cells, which had a good response to doxorubicin, both MDA-MB-231 and T47D showed high doxorubicin drug resistance. Co-treatment with various misfolding p53 aggregation inhibitors and doxorubicin found that only the HSP70 inhibitor and doxorubicin had synergistic anticancer activity in both MDA-MB-231 and T47D cells. Furthermore, this co-treatment induced cell apoptosis in MDA-MB-231, which was reversed by a pan-caspase inhibitor. Conclusions: Doxorubicin resistance caused by specific p53 mutants can be resolved by co-treatment with a HSP70 inhibitor in breast cancer cells. Full article

The objective of the presented work is the stern duct design for the JBC (Japan Bulk Carrier) hull form. Since the original duct only provides a 0.6% resistance reduction, an innovative duct will be proposed to improve the ship resistance and propulsion performance. The duct section geometry is based on the NACA (National Advisory Committee for Aeronautics) 4-digit foil series. First, we analyze whether the wake flow field and total resistance of the ship are improved, and then we investigate the self-propulsion performance for the selected ones. The research tool is the CFD (Computational Fluid Dynamics) software OpenFOAM 9 with the viscous free surface flow field modelled by the VOF (Volume of Fluid) method and the SST (Shear Stress Transport) k–ω turbulence model. The propeller effect is implemented by the MRF (Multi-Reference Frame). Compared to the original duct, two ducts, namely, NACA 7908 and NACA 6.3914, show the best (2.8%) resistance reduction in the bare hull condition. By installing both ducts, the propeller thrust decreases 6 and 5% to reach the self-propulsion point, and the behind-hull efficiency increases 7 and 6%. Both ducts save the energy, i.e., effective horsepower, by 4.3%, and produce obvious flow acceleration, achieving around 10% higher effective wake factor (1 − w). The nominal and propeller wakes are improved as well. Full article