Search Results (3,470)

Background/Objectives: Hypertension is a global health challenge. Zhengan Xifeng Decoction (ZXD), a classical traditional Chinese medicine, has shown clinical efficacy against hypertension. This study aimed to identify the bioactive constituents of ZXD and elucidate its antihypertensive mechanisms by integrating plasma UPLC–MS (ultra-performance liquid chromatography–mass spectrometry) analysis, network pharmacology, and molecular dynamics (MD) simulations. Methods: ZXD constituents and plasma-absorbed compounds were characterized by UPLC–MS. Putative targets (TCMSP, SwissTargetPrediction) were cross-referenced with hypertension targets (GeneCards, OMIM) and analyzed in a STRING protein–protein interaction network (Cytoscape) to define hub targets, followed by GO/KEGG enrichment. Selected protein–ligand complexes underwent docking, Prime MM-GBSA calculation, and MD validation. Results: A total of 72 absorbed components were identified, including 14 prototype compounds and 58 metabolites. Network pharmacology identified ten key bioactive compounds (e.g., liquiritigenin, isoliquiritigenin, and caffeic acid), 149 hypertension-related targets, and ten core targets such as SRC, PIK3CA, PIK3CB, EGFR, and IGF1R. Functional enrichment implicated cardiovascular, metabolic, and stress-response pathways in the antihypertensive effects of ZXD. Molecular docking demonstrated strong interactions between key compounds, including liquiritigenin, caffeic acid, and isoliquiritigenin, and core targets, supported by the MM-GBSA binding free energy estimation. Subsequent MD simulations confirmed the docking poses and validated the stability of the protein–ligand complexes over time. Conclusions: These findings provide mechanistic insights into the multi-component, multi-target, and multi-pathway therapeutic effects of ZXD, offering a scientific basis for its clinical use and potential guidance for future drug development in hypertension management. Full article

To address the challenges of frequent path conflicts and prolonged computation times in path planning for large-scale multi-UAV operations within urban low-altitude airspace, this study proposes a conflict-free path planning method integrating 3D Jump Point Search (JPS) and an incremental update mechanism. A hierarchical algorithmic architecture is employed: the lower level utilizes the 3D-JPS algorithm for efficient single-UAV path planning, while the upper level implements a conflict detection and resolution mechanism based on a dual-objective cost function and incremental updates for multi-UAV coordination. Large-scale UAV path planning simulations were conducted using a 3D grid model representing urban low-altitude airspace, with performance comparisons made against traditional methods. The results demonstrate that the proposed algorithm significantly reduces the number of path search nodes and exhibits superior computational efficiency for large-scale UAV path planning. Specifically, under high-density scenarios of 120 UAVs per square kilometer, the proposed DOCBS + IJPS method can reduce the conflict-free path planning time by 35.56% compared to the traditional CBS + A* conflict search and resolution algorithm. Full article

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer, with a poor prognosis due to late diagnosis, limited curative therapies, and underlying liver disease. Glutamine metabolism, a crucial pathway in cancer, remains poorly understood in HCC, which develops in an already metabolically dynamic organ. This study aimed to characterize glutamine metabolism in HCC. Glutamine metabolism in HCC was explored through in vitro analysis of neoplastic characteristics, experimental hepatocarcinogenesis in C57BL/6 mice, and examination of liver samples from patients with HCC, cirrhosis, and non-diseased liver. The evaluation included metabolite abundance and mRNA/protein expressions. In mice, tumors exhibited hyperactive glutaminolysis compared to adjacent tissue. Notably, glutaminase expression shifted from the liver isoform (GLS2) in normal and cirrhotic livers to the kidney isoform (GLS1) in HCC. In samples from patients, HCC tumors showed overexpression of glutamine synthetase and GLS1 along with a loss of GLS2 expression, providing excellent discrimination of HCC lesions from cirrhotic and normal liver samples. Inhibiting GLS1 with CB-839 significantly impacted glutamine metabolism in HCC cells while showing limited activity on normal hepatocytes. HCC tumors show reprogramming of GLS2 to GLS1, with a concomitant increase in glutamine synthetase. These characteristics can discriminate HCC from cirrhotic and normal liver tissues. Overexpressed GLS1 and loss of GLS2 within tumors convey an unfavorable prognosis in patients with HCC. Pharmacological inhibition of GLS1 in HCC cells successfully harnesses glutamine metabolism, representing an attractive target for novel therapeutic approaches. Full article

Background: The adhesion between artificial teeth and denture bases is crucial for the longevity of complete dentures. This in vitro study evaluated the shear bond strength (SBS) and failure modes between artificial teeth and denture base resins produced with conventional, milled, and 3D-printed techniques. Materials: A total of 105 specimens were fabricated and assigned to 7 groups (n = 15) combining conventional, milled, or printed denture bases with conventional, milled, or printed teeth. SBS was tested using a universal testing machine, and failure modes were classified as adhesive, cohesive, or mixed. Data were analyzed with one-way ANOVA and Tukey’s post hoc test (α = 0.05). Results: SBS significantly varied among groups (p < 0.001). The conventional base–conventional tooth group (CB-CT) showed the highest bond strength (14.9 ± 3.69 MPa), while the printed base–milled tooth group (PB-MT) had the lowest (6.58 ± 3.41 MPa). Milled base groups showed intermediate values (11.7–12.4 MPa). Conclusions: Bond strength between denture teeth and denture bases depends on the fabrication workflow. Conventional heat-cured PMMA bases exhibited the most reliable adhesion, while milled bases demonstrated satisfactory performance with optimized bonding. Printed bases showed reduced and variable adhesion, suggesting the need for improved bonding protocols before their widespread clinical application in definitive prostheses. Full article

Background: Glutamate transporter 1 (GLT-1) plays a vital role in maintaining glutamate homeostasis in the body. A decreased GLT-1 expression in astrocytes can heighten neuronal sensitivity to glutamate excitotoxicity after traumatic brain injury (TBI). Despite its significance, the mechanisms behind the reduced expression of GLT-1 following TBI remain poorly understood. After TBI, the endocannabinoid 2-arachidonoyl glycerol (2-AG) is elevated several times. 2-AG is known to inhibit key positive transcriptional regulators of GLT-1. This study aims to investigate the role of 2-AG in regulating GLT-1 expression and to uncover the underlying mechanisms involved. Methods: A controlled cortical impact (CCI) model was used to establish a TBI model in C57BL/6J mice. The CB1 receptor antagonist (referred to as AM281) and the monoacylglycerol lipase (MAGL) inhibitor (referred to as JZL184) were administered to investigate the role and mechanism of 2-AG in regulating GLT-1 expression following TBI. Behavioral tests were conducted to assess neurological functions, including the open field, Y-maze, and novel object recognition tests. Apoptotic cells were identified using the TUNEL assay, while Western blot analysis and immunofluorescence were employed to determine protein expression levels. Results: The expression of GLT-1 in the contused cortex and hippocampus following TBI showed an initial decrease, followed by a gradual recovery. It began to decrease within half an hour, reached its lowest level at 2 h, and then gradually increased, returning to normal levels by 7 days. The administration of AM281 alleviated neuronal death, improved cognitive function, and reversed the reduction of GLT-1 caused by TBI in vivo. Furthermore, 2-AG decreased GLT-1 expression in astrocytes through the CB1-CREB signaling pathway. Mechanistically, 2-AG activated CB1, which inhibited CREB phosphorylation in astrocytes. This decreased GLT-1 levels and ultimately increased neuronal sensitivity to glutamate excitotoxicity. Conclusions: Our research demonstrated that the upregulation of GLT-1 expression effectively mitigated neuronal apoptosis and cognitive dysfunction by inhibiting the CB1-CREB signaling pathway. This finding may offer a promising therapeutic strategy for TBI. Full article

Semantic segmentation of building facade images has enabled a lot of intelligent support for architectural research and practice in the last decade. However, the classifiers for semantic segmentation usually predict facade elements (e.g., windows) as graphics in irregular shapes. The non-smooth edges and hard-to-define shapes impede the further use of the predicted graphics. This study proposes a method to regularize the predicted graphics following the prior knowledge of composition principles of building facades. Specifically, we define four types of boxes for each predicted graphic, namely minimum circumscribed box (MCB), maximum inscribed box (MIB), candidate box (CB), and best overlapping box (BOB). Based on these boxes, a three-stage process, consisting of denoising, BOB finding, and BOB stacking, was established to regularize the predicted graphics of facade elements into basic rectilinear polygons. To compare the proposed and existing methods of graphic regularization, an experiment was conducted based on the predicted graphics of facade elements obtained from four pixel-wise annotated building facade datasets, Irregular Facades (IRFs), CMP Facade Database, ECP Paris, and ICG Graz50. The results demonstrate that the graphics regularized by our method align more closely with real facade elements in shape and edge. Moreover, our method avoids the prevalent issue of correctness degradation observed in existing methods. Compared with the predicted graphics, the average IoU and F1-score of our method-regularized graphics respectively increase by 0.001–0.017 and 0.000–0.012 across the datasets, while those of previous method-regularized graphics decrease by 0.002–0.021 and 0.002–0.015. The regularized graphics contribute to improving the precision and depth of semantic segmentation-based applications of building facades. They are also expected to be useful for the exploration of data mining on urban images in the future. Full article

Background: Cervical cancer remains a major global health concern, with high recurrence rates in advanced stages. [¹⁸F]FDG PET/CT provides prognostic biomarkers such as SUV, MTV, and TLG, though these are not routinely integrated into clinical protocols. Radiomics offers quantitative analysis of tumor heterogeneity, supporting risk stratification. Purpose: To evaluate the prognostic value of clinical and radiomic features for disease-free survival (DFS) in locoregionally advanced cervical cancer using machine learning (ML). Methods: Sixty-three patients (mean age 47.9 ± 14.5 years) were diagnosed between 2015 and 2020. Radiomic features were extracted from pre-treatment PET/CT (IBSI-compliant PyRadiomics). Clinical variables included age, T-stage, Dmax, lymph node involvement, SUVmax, and TMTV. Forty-two models were built by combining six feature-selection techniques (UCI, MD, MI, VH, VH.VIMP, IBMA) with seven ML algorithms (CoxPH, CB, GLMN, GLMB, RSF, ST, EV) using nested 3-fold cross-validation with bootstrap resampling. External validation was performed on 95 patients (mean age 50.6 years, FIGO IIB–IIIB) from an independent cohort with different preprocessing protocols. Results: Recurrence occurred in 31.7% (n = 20). SUVmax of lymph nodes, lymph node involvement, and TMTV were the most predictive individual features (C-index ≤ 0.77). The highest performance was achieved by UCI + EV/GLMB on combined clinical + radiomic features (C-index = 0.80, p < 0.05). For single feature sets, IBMA + RSF performed best for clinical (C-index = 0.72), and VH.VIMP + GLMN for radiomics (C-index = 0.71). External validation confirmed moderate generalizability (best C-index = 0.64). Conclusions: UCI-based feature selection with GLMB or EV yielded the best predictive accuracy, while VH.VIMP + GLMN offered superior external generalizability for radiomics-only models. These findings support the feasibility of integrating radiomics and ML for individualized DFS risk stratification in cervical cancer. Full article

Harnessing solar energy is crucial for applications such as water desalination through solar collectors, where efficient conversion of solar radiation into thermal energy is required. In this study, electroless nickel–phosphorus (Ni-P) coatings and their carbon black (CB) nanoparticle composites were successfully deposited and evaluated as selective solar absorbers. The coatings exhibited compact, crack-free, and amorphous structures composed mainly of Ni(OH)₂ and NiOOH, as confirmed by SEM-EDS, XRD, FTIR, and Raman analyses. Increasing the pH enhanced the deposition rate and coating thickness while reducing the phosphorus content. Incorporation of CB nanoparticles was confirmed, though it slightly decreased coating thickness. Optical characterization revealed high absorptance and low emissivity across all samples, with the Ni-P coating produced at higher pH (C1) achieving the best performance (brightness L* = 29.0; figure of merit α − ε = 0.84). Aging tests further demonstrated the resilience of this sample, maintaining a figure of merit of 0.81. These findings establish Ni-P coatings, particularly at higher pH, as promising and safer alternatives to conventional chromium-based solar selective coatings. Full article

Cannabidiol (CBD) and other phytocannabinoids are gaining attention for their therapeutic potential in cardiovascular disease (CVD), the world’s leading cause of death. This review highlights advances in understanding the endocannabinoid system, including CB1 and CB2 receptors, and the mechanisms by which CBD exerts anti-inflammatory, antioxidative, vasoprotective, and immunomodulatory effects. Preclinical and translational studies indicate that selective activation of CB2 receptors may attenuate atherogenesis, limit infarct size in ischemia–reperfusion injury, decrease oxidative stress, and lessen chronic inflammation, while avoiding the psychotropic effects linked to CB1. CBD also acts on multiple molecular targets beyond the CB receptors, affecting redox-sensitive transcription factors, vascular tone, immune function, and endothelial integrity. Early clinical trials and observational studies suggest that CBD may lower blood pressure, improve endothelial function, and reduce sympatho-excitatory peptides such as catestatin, with a favorable safety profile. However, limited bioavailability, small sample sizes, short study durations, and uncertainty about long-term safety present challenges to its clinical use. Further research is needed to standardize dosing, refine receptor targeting, and clarify the role of the endocannabinoid system in cardiovascular health. Overall, current evidence supports CBD’s promise as an adjunct in CVD treatment, but broader clinical use requires more rigorous, large-scale studies. Full article

Background: Neonatal seizures are critical neurological events with long-term implications for brain development. Standard antiseizure medications, such as phenobarbital, often yield suboptimal seizure control and may be associated with neurotoxicity. This narrative review explores the role of vitamin B6 as a precision therapy in neonatal seizure syndromes, particularly in pyridoxine-responsive conditions. Methods: We conducted a narrative review of the biochemical functions of vitamin B6, focusing on its active form, pyridoxal 5′-phosphate (PLP), and its role as a coenzyme in neurotransmitter synthesis. We examined the genetic and metabolic disorders linked to vitamin B6 deficiency, such as mutations in pyridox(am)ine 5’-phosphate oxidase (PNPO), Aldehyde Dehydrogenase 7 Family Member A1 (ALDH7A1), alkaline locus phosphatase (ALPL), and cystathionine β-synthase (CBS), and discussed the clinical rationale for empirical administration in acute neonatal seizure settings. Results: Vitamin B6 is essential for the synthesis of gamma-aminobutyric acid (GABA), dopamine, and serotonin, with PLP-dependent enzymes such as glutamic acid decarboxylase and aromatic L-amino acid decarboxylase playing central roles. Deficiencies in PLP due to genetic mutations or metabolic disruptions can result in treatment-resistant neonatal seizures. Early supplementation, especially in suspected vitamin B6-dependent epilepsies, may provide both diagnostic clarity and seizure control, potentially reducing exposure to conventional antiseizure medications. Conclusions: Vitamin B6-responsive epilepsies highlight the clinical value of mechanism-based, individualized treatment approaches in neonatology. Incorporating genetic and metabolic screening into seizure management may improve outcomes and aligns with the principles of precision medicine. Full article

Background/Objectives: The relationship between thrombus imaging features and the natural evolution of stroke remains poorly defined. We aimed to investigate the associations between thrombus characteristics on CT and perfusion parameters, as well as subsequent infarct progression, in untreated patients experiencing an anterior circulation acute ischemic stroke (AIS). Methods: This retrospective analysis enrolled 81 untreated patients with AIS who underwent baseline non-contrast CT (NCCT), CT angiography (CTA), CT perfusion (CTP), and a follow-up NCCT. We evaluated the thrombus length, location, and clot burden score (CBS). CTP parameters included the ischemic core, hypoperfused tissue, and penumbra volumes. Infarct growth was the difference between the final infarct volume on a follow-up NCCT and the initial core volume on CTP. Univariate and multivariate regression models were performed. Results: Higher CBS values and shorter thrombi are associated with a reduced ischemic core (coefficients B of −3.9 and 0.88, p < 0.01), diminished hypoperfused tissue (coefficients B of −12.2 and 2.87, p < 0.001), and smaller penumbra volume (coefficients B of −7.9 and 1.99, p < 0.001). More distal occlusions were associated with smaller perfusion deficits. Importantly, a higher CBS and more distal thrombus location were significantly associated with a smaller final infarct volume and infarct growth volume. Conclusions: In untreated AIS patients, a lower thrombus burden (higher CBS, shorter length, distal location) is associated with more favorable baseline perfusion parameters and predicts a slower, less severe natural evolution of AIS. These findings underscore the prognostic value of baseline thrombus characteristics in determining the intrinsic course of a stroke. Full article

Self-fluxing Ni-based coatings (NiCrFeBSiC) were deposited through gas-flame spraying and evaluated in three conditions: as-sprayed, flame-remelted, and furnace-heat-treated (1025 °C/5 min). Phase analysis (XRD) revealed FeNi₃ together with strengthening carbides/borides (e.g., Cr₇C₃, Fe₂₃(C,B)₆); post-treatments increased lattice order. Cross-sectional image analysis showed progressive densification (thickness ~805→625→597 µm) and a drop in porosity from 7.866% to 3.024% to 1.767%. Surface roughness decreased from Ra = 31.860 to 14.915 to 13.388 µm. Near-surface microhardness rose from 528.7 ± 2.3 to 771.6 ± 4.6 to 922.4 ± 5.7 HV, while adhesion strength (ASTM C633) improved from 18 to 27 to 34 MPa. Wettability followed the densification trend, with the contact angle increasing from 53.152° to 79.875° to 89.603°. Under dry ball-on-disk sliding against 100Cr6, the friction coefficient decreased and stabilized (0.648 ± 0.070 → 0.173 ± 0.050 → 0.138 ± 0.003), and the counterbody wear-scar area shrank by ~95.6% (0.889 → 0.479 → 0.0395 mm²). Wear-track morphology evolved from abrasive micro-cutting (as-sprayed) to reduced ploughing (flame-remelted) and a polishing-like regime with a thin tribo-film (furnace). Potentiodynamic tests indicated the lowest corrosion rate after furnace treatment (CR ≈ 0.005678 mm·year⁻¹). Overall, furnace heat treatment provided the best structure–property balance (lowest porosity and Ra, highest HV and adhesion, lowest and most stable μ, and superior corrosion resistance) and is recommended to extend the service life of NiCrFeBSiC coatings under dry sliding. Full article

Background/Objectives: Diabetic neuropathy (DN) is a prevalent complication of diabetes mellitus, affecting up to 50% of long-term patients and causing significant pain, reduced quality of life, and healthcare burden. Conventional treatments, including anticonvulsants, antidepressants, and opioids, offer limited efficacy and are associated with adverse effects. Emerging evidence suggests that cannabis, acting via the endocannabinoid system, may provide analgesic and neuroprotective benefits. This study evaluates the long-term effects of inhaled cannabis as adjunctive therapy for refractory painful DN. Inhaled cannabis exhibits rapid onset pharmacokinetics (within minutes, lasting 2–4 h) due to pulmonary absorption, targeting CB1 and CB2 receptors to modulate pain and inflammation. Methods: In this prospective, observational study, 52 patients with confirmed painful DN, unresponsive to at least three prior analgesics plus non-pharmacological interventions, were recruited from a single clinic. Following a 1-month washout, patients initiated inhaled medical-grade cannabis (20% THC, <1% CBD), titrated individually. Assessments occurred at baseline and annually for 5 years, including the Brief Pain Inventory (BPI) for pain severity and interference; the degree of pain relief; Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score; HbA1c; and medication usage. Statistical analyses used repeated-measures ANOVA, Kruskal–Wallis tests, Welch’s t-tests, and Pearson’s correlations via Analyze-it for Excel. Results: Of 52 patients (mean age 45.3 ± 17.8 years; 71.2% male; diabetes duration 23.3 ± 17.8 years), 50 completed follow-up visits. Significant reductions occurred in BPI pain severity (9.0 ± 0.8 to 2.0 ± 0.7, p < 0.001), interference (7.5 ± 1.7 to 2.2 ± 0.9, p < 0.001), LANSS score (19.4 ± 3.8 to 10.2 ± 6.4, p < 0.001), and HbA1c (9.77% ± 1.50 to 7.79% ± 1.51, p < 0.001). Analgesic use decreased markedly (e.g., morphine equivalents: 66.8 ± 49.2 mg to 4.5 ± 9.6 mg). Cannabis dose correlated positively with pain relief (r = 0.74, p < 0.001) and negatively with narcotic use (r = −0.43, p < 0.001) and pain interference (r = −0.43, p < 0.001). No serious adverse events were reported; mild side effects (e.g., dry mouth or euphoria) occurred in 15.4% of patients. Conclusions: Inhaled cannabis showed sustained pain relief, improved glycemic control, and opioid-sparing effects in refractory DN over 5 years, with a favorable safety profile. These findings are associative due to the observational design, and randomized controlled trials (RCTs) are needed to confirm efficacy and determine optimal usage, addressing limitations such as single-center bias and small sample size (n = 52). Future studies incorporating biomarker analysis (e.g., endocannabinoid levels) could elucidate mechanisms and enhance precision in cannabis therapy. Full article

TGR5 has emerged as a promising therapeutic target for obesity and metabolic disorders due to its regulatory roles in energy expenditure, glucose homeostasis, thermogenesis, and gut hormone secretion. This review summarizes the structural mechanisms of TGR5 activation, focusing on orthosteric and allosteric ligand interactions, toggle switch dynamics, and G protein coupling based on cryo-EM and docking-based models. A wide range of bioactive natural compounds including oleanolic acid, curcumin, betulinic acid, ursolic acid, quinovic acid, obacunone, nomilin, and 5β-scymnol are examined for their ability to modulate TGR5 signaling and elicit favorable metabolic effects. Molecular docking simulations using CB-Dock2 and PDB ID 7BW0 revealed key interactions within the orthosteric pocket, supporting their mechanistic potential as TGR5 agonists. Emerging strategies in TGR5-directed drug development are also discussed, including gut-restricted agonism to minimize gallbladder-related side effects, biased and allosteric modulation to fine-tune signaling specificity, and AI-guided optimization of natural product scaffolds. These integrated insights provide a structural and pharmacological framework for the rational design of safe and effective TGR5-targeted therapeutics. Full article

Obesity is a complex, multifactorial disease and a growing global health challenge associated with type 2 diabetes, cardiovascular disorders, cancer, and reduced quality of life. The existing pharmacological therapies are characterized by their limited number and efficacy, and safety concerns further restrict their utilization. This review synthesizes extensive knowledge regarding the role of the endocannabinoid system (ECS) in the pathogenesis of obesity, as well as its potential as a therapeutic target. A thorough evaluation of preclinical and clinical data concerning endocannabinoid ligands, cannabinoid receptors (CB1, CB2), their genetic variants, and pharmacological interventions targeting the ECS was conducted. Literature data suggests that the overactivation of the ECS may play a role in the pathophysiology of excessive food intake, dysregulated energy balance, adiposity, and metabolic disturbances. The pharmacological modulation of ECS components, by means of CB1 receptor antagonists/inverse agonists, CB2 receptor agonists, enzyme inhibitors, and hybrid or allosteric ligands, has demonstrated promising anti-obesity effects in animal models. However, the translation of these findings into clinical practice remains challenging due to safety concerns, particularly neuropsychiatric adverse events. The development of novel strategies, including peripherally restricted compounds, hybrid dual-target agents, dietary modulation of endocannabinoid tone, and non-pharmacological interventions, promises to advance the field of obesity management. Full article