Search Results (6,519)

In the present study, a series of isoxazole derivatives were severally evaluated for their antifungal activity against the yeast Candida albicans and molds such as Aspergillus niger, Aspergillus flavus, and Fusarium oxysporum. The results demonstrate that the isoxazole derivatives exhibit considerable antifungal potential, particularly isoxazole-sulfonate ester 4b (Ar= 4-(Cl)C₆H₄, Ar′= 4-(CH₃)C₆H₄), which was found to be active with significant inhibition zones; the diameters of the C. albicans and F. oxysporum samples were measured at 17.00 ± 0.00 mm and 14.00 ± 0.00 mm, respectively. Furthermore, compounds 4a (Ar= 4-(CH₃)C₆H₄, Ar′= 4-(CH₃)C₆H₄), 4c (Ar: 4-(Cl)C₆H₄, Ar′: 4-(NO₂)C₆H₄) and 4d (Ar: 4-(Cl)C₆H₄, Ar′: 3-(Cl)-2-(OCH₃)C₆H₃) demonstrated MIC and MFC values of 20 µg/mL against C. albicans. In addition, the anti-hemolytic activity of these derivatives was evaluated. Compounds 4a, 4e (Ar: 4-(Cl)C₆H₄, Ar′: 3,4-(OCH₃)₂C₆H₃) and aroylisoxazole 3a (Ar: 4-(CH₃)C₆H₄) demonstrated a high degree of anti-hemolytic activity (>99%) at all concentrations evaluated (10, 15, and 20 mg/mL). Molecular docking and molecular dynamics studies over 200 ns revealed protein–ligand complexes to have high affinity and stability, which agrees with the experimental results. The compounds 4d, 4e, and 3a have shown significant interaction with the target proteins of C. albicans, A. flavus, and F. oxysporum, respectively. The results have revealed that the major interaction sites are hydrogen bonding, hydrophobic interactions, and the presence of a water molecule, especially with key residues like TYR_84, ASP_120, SER_90, and THR_89. The crystal structure of compound 4a was also obtained. Full article

Background/Objectives: Excessive trabeculation of the left ventricle, previously known as left ventricular non-compaction (LVNC), is a rare phenotypic trait whose mechanisms and pathogenesis still remain conflictual. Its presentations may range from heart failure to embolism and, most importantly, ventricular arrhythmias (VAs). This study aims to find novel predictive factors for the occurrence of potentially fatal VAs in patients with left ventricular hypertrabeculation. Methods: All consecutive patients meeting the echocardiographic (Chin, Jenny or Stöllberger) and/or MRI criteria (Petersen) for hypertrabeculation were prospectively enrolled from October 2009 to December 2023. The primary outcome was a composite of sudden cardiac death, sustained ventricular tachycardias (sVTs), ventricular fibrillation (VF) or appropriate implantable cardioverter defibrillator (ICD) interventions. The secondary outcome was a composite of cardiovascular death and cardiovascular hospitalizations. Results: Overall, 64 patients (41 males, mean age 46 ± 19 years old) were enrolled and followed for a median time of 2.2 years. Six patients (9.4%) experienced a composite outcome at eight years, three with previous sVTs and three with previous non-sustained VTs (nsVTs). The strongest predictor of the primary endpoint was the anamnesis of nsVTs and sVTs before LVNC diagnosis. In addition, nsVTs and sVTs were significantly associated with the secondary outcome. Conclusions: Hypertrabeculation of the left ventricle is a complex and poorly understood condition whose status of cardiomyopathy is currently challenged. In our population, patients with a trabecular pattern experienced a high incidence of VAs, cardiovascular death and hospitalizations. VAs before LVNC diagnosis were predictive of the outcome independently from systolic function. Full article

NS4A plays a role in forming the flavivirus replication complex, which inhibits apoptosis in host cells by inducing autophagy, thereby promoting viral replication. The host protein ENO1 interacts with NS4A, but the precise mechanism underlying this interaction and its role in viral replication remain unclear. In this study, we identified ZIKV NS4A^1–73 as a key regulator of replication and infection cycles in both temporal and spatial dimensions. Through surface plasmon resonance (SPR) analysis, we demonstrated that ENO1 directly interacts with NS4A^1–73. This critical binding inhibits the enzymatic activity of ENO1 and reduces cellular lactate and ATP production. Our findings suggest that ZIKV NS4A may effectively impede cellular metabolism by targeting the host factor ENO1, thus disrupting the glycolytic process. This insight could open new avenues for targeting ZIKV and similar viruses in therapeutic strategies. Full article

Flying Ad Hoc Networks (FANETs) composed of multiple unmanned aerial vehicles (UAVs) are a promising solution for emergency wireless communications when terrestrial infrastructure is unavailable. However, ensuring reliable Quality of Service (QoS) in these highly dynamic networks remains challenging due to topology changes, varying propagation conditions, and congestion. This work proposes a lightweight machine learning-based QoS optimization framework for multi-UAV emergency communications that combines realistic mobility modeling, empirical channel measurements, and adaptive traffic prioritization. UAV mobility patterns are generated with ArduSim, while LoS/NLoS propagation models are derived from real UAV flight experiments and integrated into ns-3. Multiple supervised machine learning algorithms—including Decision Trees, Random Forest, Support Vector Machines, k-NN, Gradient Boosting, and CatBoost—are trained using four input features derived from the network state: ${\mathrm{CBR}}_{\mathrm{src}}$, ${\mathrm{QP}}_{\mathrm{src}}$, ${\mathrm{CBR}}_{\mathrm{dst}}$, and ${\mathrm{QP}}_{\mathrm{dst}}$. Simulation results show that the proposed AI SMOTE EMERGENCY scheme, based on CatBoost, improves the Packet Delivery Ratio (PDR) by approximately 43% over the No-QoS baseline, achieving 89–93% delivery across all four application ports. Compared with EDCA, the proposed scheme maintains reliable delivery for all services, increases emergency throughput by 34–36%, and reduces end-to-end delay by about 70%. In addition, the higher delivery reliability translates into clear communication energy benefits, reducing energy waste across all evaluated topologies when compared with the No-QoS baseline. The inference time remains below 0.002 s, supporting real-time QoS adaptation in resource-constrained UAV networks. Full article

Background: Acquired resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib, often mediated by EGFR triple mutations, poses a major clinical challenge in non-small cell lung cancer (NSCLC) treatment. Among these, some rare mutations, such as L858R/T790M/L792H and L858R/T790M/G796R, create steric hindrance that directly interferes with osimertinib binding, yet effective targeted therapeutic strategies for these specific mutations remain lacking. Cudratricusxanthone A (CTXA), a natural xanthone derivative isolated from Cudrania tricuspidata Bur., has demonstrated various pharmacological activities, but its effects against EGFR triple-mutant NSCLC have not been systematically investigated. Methods: Stable Ba/F3 and NIH/3T3 cell lines expressing EGFR L858R/T790M/L792H or L858R/T790M/G796R triple mutations were generated via electroporation. The antiproliferative effects of CTXA were evaluated by MTT/MTS assays, colony formation, and wound healing assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Protein expression of EGFR signaling pathway components (p-EGFR, p-ERK, p-AKT, p-STAT3) and cell cycle regulators (Cyclin D1, CDK4) were examined by Western blotting. Molecular docking and 200 ns molecular dynamics simulations were performed to investigate the stability and binding modes of CTXA to the mutant EGFR kinase domains. Results: The successfully established triple-mutant cell lines exhibited high EGFR expression, IL-3-independent growth, and significant resistance to osimertinib. CTXA inhibited the proliferation of all triple-mutant cell lines in a time- and concentration-dependent manner, with 48 h IC₅₀ values ranging from 0.362 to 2.488 μM. Mechanistically, CTXA suppressed EGFR autophosphorylation and downregulated downstream p-ERK, p-AKT, and p-STAT3. CTXA induced G1 phase cell cycle arrest by downregulating Cyclin D1 and CDK4, significantly promoted apoptosis, and inhibited cell migration. Molecular docking revealed that while osimertinib binding was blocked by steric hindrance from His-792 or Arg-796, CTXA adapted to the mutated ATP-binding pockets through multiple hydrogen bonds and extensive hydrophobic interactions. Molecular dynamics simulations confirmed the stable binding of CTXA to both mutant EGFR proteins over the 200 ns simulations. Conclusions: This study demonstrates for the first time that the natural compound CTXA possesses antitumor efficacy against EGFR L858R/T790M/L792H and L858R/T790M/G796R mutants by regulating EGFR-ERK/AKT/STAT3 signaling. Our findings position CTXA as a promising lead compound for tackling this challenging form of acquired resistance and highlight the value of natural products in multi-target antitumor drug discovery. Full article

Silicon carbide (SiC) MOSFETs are promising for high-efficiency, high-power-density power conversion owing to their high breakdown capability, fast switching speeds, and low switching losses. However, parasitic parameters can cause severe voltage/current overshoot and oscillation during high-speed switching, leading to electromagnetic interference and degraded performance. To address this issue, this study analyzes the mechanisms of current overshoot during turn-on and voltage overshoot during turn-off, and presents an adaptive active gate driver chip based on a three-stage driving current control strategy. By identifying key switching intervals and regulating segmented gate-drive current, the proposed chip can effectively suppress overshoot while reducing the switching loss. During turn-on, cross-cycle switching point regulation based on Miller plateau tracking is proposed to achieve adaptive control under different operating conditions, while the turn-off control is realized by peak sampling of the drain–source voltage. The chip was fabricated in the 180 nm BCD process. Compared with a conventional passive driver, the proposed driver reduces turn-on loss by 35.1% at 400 V/40 A under a dv_DS/dt of 4.8 V/ns and reduces turn-off loss by 33.2% under a v_DS overshoot of nearly 50 V. These results show that the proposed chip improves SiC MOSFET switching performance and provides a practical gate-driving solution. Full article

Panzhihua-type V–Ti magnetite deposits in the Panxi region are hosted in mafic–ultramafic intrusions, and their exploration potential depends strongly on the deep distribution of ore-bearing intrusions. High-resolution 3D magnetic inversion is an effective tool to image the geometry of these intrusions. Using 1:50,000 aeromagnetic data, we applied an unsupervised deep learning inversion to obtain the 3D magnetic susceptibility structure of related intrusions. The results show that magnetic anomalies are mainly NS and NEE trending, with minor NNW-trending features. NS-trending sources occur in the Baima–Miyi–Hongge zone between the Xigeda–Yuanmou and Anninghe faults, while NEE-trending anomalies lie west of the Xigeda–Yuanmou fault and east of the Chenghai fault. Integrated geological analysis reveals two Late Variscan rift systems: the Anninghe rift and the Panzhihua rift. Deep fault-controlled magma ascent and emplacement, forming the Emeishan large igneous province, are associated with strongly magnetic intrusions. Mantle plume-derived magmas, differentiated in shallow and deep magma chambers, generate well-differentiated layered complexes at depths < 10 km with magnetic intensities of 5–10 A/m. Shear structures within paleorifts provide favorable emplacement conditions and controlled ore localization. We propose a three-in-one ore-controlling mechanism involving rift systems, intrusive rocks, and shear structures for Panzhihua-type V–Ti magnetite mineralization. Full article

Background and Objectives: Given the high rates of anterior cruciate ligament graft rupture in the pediatric population, lateral extra-articular tenodesis (LET) is increasingly used in combination with anterior cruciate ligament reconstruction (ACLR) to mitigate the risk of re-injury. This study aimed to compare postoperative postural stability between patients undergoing ACLR with and without LET. It was hypothesized that postural stability would be comparable between patients with and without LET. Materials and Methods: This retrospective, single-center, double-surgeon case–control study included patients who underwent primary ACLR using hamstring tendon autografts between January 2022 and May 2025. Postoperative postural stability was assessed using the Biodex Stability System (BSS) global stability index (GSI), which was the primary outcome of interest. Demographic and surgical data were collected as well as all postoperative GSIs. GSI comparisons between the LET and no-LET groups were made at ≤6 months and >6 months postoperatively. Secondary analysis compared GSI differences between the healthy and operated legs. Results: Among 229 patients screened, 100 met the inclusion criteria (median age, 16 years [IQR, 15–17]); 65 underwent LET and 35 did not, and 54 were female (54%). The groups were comparable on demographic and surgical data (p-value: n.s.). No operated leg GSI difference was observed between the LET and no-LET groups at ≤6 months (p = 0.372) and >6 months postoperatively (p = 0.424). Patients with LET had significantly better (lower) healthy leg GSIs (Mean ± SD; 2.7 ± 0.9) than no-LET patients (3.9 ± 1.8) at >6 months postoperatively (p = 0.004). At ≤6 months, patients showed better GSIs on their operated limb (Median [IQR]; 2.6 [2.1–3.9]) compared to the healthy limb (3.5 [2.3–4.6]) (p = 0.003). This difference disappeared at the latest follow-up. Conclusions: The addition of LET concomitant with ACLR was not associated with a significant difference in postural stability, as assessed by the GSI from the BSS. However, given the sample size and study limitations, these findings should be interpreted with caution. Increased attention to the healthy limb during ACLR rehabilitation may be warranted, particularly in the early postoperative period (<6 months). Further studies with larger cohorts are needed to confirm these observations. Full article

Eye cosmetic products are widely used and applied in close proximity to the ocular surface, making their microbiological safety particularly important. The aim of this study was to assess bacterial contamination in used eye cosmetic products, characterize the antimicrobial resistance profiles of the isolated bacteria, and perform molecular genotypic analysis. A total of 71 samples, including mascara, eyeliner, and eyeshadow, were analyzed. Microbiological analysis revealed that Bacillus spp. and coagulase-negative staphylococci (CoNS) were the predominant microorganisms, while no major pathogens such as Staphylococcus aureus, Escherichia coli, or Pseudomonas aeruginosa were detected. Antimicrobial susceptibility testing demonstrated high susceptibility of isolates to gentamicin, vancomycin, and linezolid, whereas resistance to benzylpenicillin and clindamycin was observed among Staphylococcus spp. Molecular identification based on 16S rRNA gene sequencing confirmed the presence of Bacillus licheniformis, Bacillus subtilis, Staphylococcus epidermidis, and Staphylococcus warneri, with sequences showing high similarity to globally distributed strains. Although the detected microorganisms were predominantly opportunistic, their presence in products applied near the eyes suggests a potential risk of microbial transfer to the ocular surface. These findings highlight the importance of proper hygiene practices, regular product replacement, and effective quality control measures to minimize microbial contamination and associated health risks. Full article

2,4-Dichlorophenoxyacetic acid (2,4-D) is a vital exogenous auxin for the induction and proliferation of litchi embryogenic callus. At present, its molecular regulation mechanism remains unclear. In this study, transcriptome sequencing samples were selected based on different cell growth phenotypes observed in ‘Feizixiao’ litchi embryogenic callus cultured in liquid medium with or without 2,4-D. By integrating transcriptome profiling with weighted gene co-expression network analysis (WGCNA), we identified key genes and signaling pathways dynamically responsive to 2,4-D concentration changes. We identified 558 commonly differentially expressed genes (DEGs), of which 117 were up-regulated and 387 were down-regulated; functional enrichment analysis revealed significant enrichment in the “plant hormone signal transduction” and “phenylpropanoid biosynthesis” pathways. In the former pathway, genes such as AUX28, GH3.17, GH3.6, and ARR5 were up-regulated; in the latter, by comparison, β-glucosidase 47 and Peroxidase 61 exhibited increased expression levels induced by 2,4-D. Furthermore, among these DEGs, 57 transcription factors belonged to 24 families. Notably, VRN1, FEZ, and DOF5.4 were significantly and rapidly induced by 2,4-D. WGCNA results demonstrated a significant positive correlation between the yellow module and 2,4-D treatment. Small heat shock protein (sHSP) genes constituted the core hub genes in the yellow module. Through Venn analysis of DEGs and key modules, 38 cross-genes were identified, of which non-specific lipid-transfer protein-like genes (nsLTP) were found to be specifically up-regulated without 2,4-D. The transcription factors and genes identified work in synergy to ensure the formation and sustained proliferation of embryogenic callus by precisely regulating the dynamic balance of auxin and cytokinin within cells and maintaining the stability of cell structure. Our findings provide a crucial theoretical foundation for understanding the molecular mechanism of 2,4-D in regulating litchi embryogenic callus proliferation. Full article

Background/Objectives: Low vitamin D (VD) has been associated with diabetic kidney disease (DKD). Nevertheless, VD normality concentrations remain under discussion. Objectives: To evaluate VD concentrations in early and advanced DKD stages according to the Endocrine Society and Institute of Medicine standards in patients with type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study included 80 patients with T2DM and DKD in early (urine albumin–creatinine ratio (UACR) between 30 and 299 mg/g), group 1 (n = 29), and advanced stage (UACR ≥ 300 mg/g), group 2 (n = 51). Results: Compared to group 1, patients in group 2 showed lower 25(OH)D concentrations (26.7 ± 10.1 vs. 30.2 ± 8.0 ng/mL; p ≤ 0.05). In group 2, when the serum VD concentrations were stratified according to the Endocrine Society, VD concentrations ≥ 30 ng/mL were associated with a considerably reduction in UACR compared with VD < 20 ng/mL (365.9 ± 268.3 vs. 937.6 ± 634 mg/g; p < 0.05), but not when compared to the range of 20–29.9 ng/mL (739.8 ± 1138 vs. 937.6 ± 634 mg/g; p = NS). Additionally, in this group, our regression model showed that each unit increase in VD was associated with a UACR reduction of 26.1 mg/g (R² = 0.103; p < 0.05). Conclusions: Higher vitamin D concentrations were associated with improved UACR only in clinical DKD, particularly when VD was at least 30 ng/mL. Full article

The detailed mechanism and sequence by which tick-borne flaviviruses (TBFVs), such as Langat virus (LGTV), infect and disseminate in arthropod hosts remain undefined. To begin characterizing these processes, we used artificial membrane feeding chambers to feed adult Ixodes scapularis ticks with blood containing LGTV. At 24, 48, 72, and 96 hours (h) after attachment, we removed and dissected the partially fed ticks to obtain the midgut and salivary glands. Histology confirmed infection in cells of the digestive epithelium lineage; infection was noted in midgut generative cells and the more differentiated functional digestive cells over the course of feeding. The viral envelope (E) protein, nonstructural protein 3 (NS3), and double-stranded RNA (dsRNA) were readily detected in these cells by 48 h after infection. Parallel analysis indicated that cells in salivary gland acini were also infected by 48 h, where virus target cells appeared to be the granular cells in acini types II and III. Thus, both salivary glands and midgut showed direct evidence of infection by 48 h. Although viral staining was not observed at 24 h, when organs were removed at 24 h and individually cultured ex vivo, the virus was detected. Taken together, our results provide evidence of LGTV infection in both the salivary glands and midgut within the first 24 h of a blood meal. The findings should prompt a reevaluation of the systemic dissemination of TBFV in infected ticks. Full article

Background: Triple−negative breast cancer (TNBC) remains among the most aggressive and therapeutically unresponsive subtypes due to the absence of ER, PR, and HER2 targets. Casein Kinase II (CK2), a pleiotropic serine/threonine kinase overexpressed in TNBC, represents a compelling target for rational drug design. Methods: Here, we present an AI−integrated benchmarking framework combining virtual drug discovery, molecular dynamics simulations, machine learning−driven QSAR modeling, and quantum−mechanical electronic structure analysis to identify potent CK2 inhibitors from natural product chemical space. Results: A validated XP docking protocol (ROC–AUC = 0.748) screened ~480,000 compounds, yielding seven hits, with superior binding to the reference inhibitor CX−4945. Among these, Anastatin B, 3,4,8,9,10−pentahydroxy−dibenzo−[b,d]pyran−6−one, Rhein, and aloe emodin acetate exhibited highly favorable docking scores (−11.6 to −13.1 kcal mol⁻¹) and stable 200 ns binding dynamics, reflected by RMSD ≤ 2 Å and compact Rg trajectories. MM−PBSA/MM−GBSA analyses confirmed robust thermodynamic stability, while DFT−derived HOMO–LUMO gaps (3.8–4.3 eV) suggested optimal electronic reactivity for kinase inhibition. Machine learning QSAR models demonstrated strong predictive performance, with the best stacking models achieving test R² ≈ 0.69 and consistent cross−validation performance (CV R² ≈ 0.66–0.69), supporting reliable prediction of pIC₅₀ values and prioritization of top−ranked scaffolds. Conclusions: Collectively, this integrative framework bridges AI−based learning and biophysical validation, establishing a reproducible paradigm for de novo CK2 inhibitor discovery in TNBC. Full article

Background: The well-established biopharmaceutical advantages provided by nanosuspensions (NSs) make their conversion into solid oral dosage forms particularly appealing for improving both patients’ compliance and product stability. However, such a transformation continues to represent a significant challenge. Aim: This study explored manual wet granulation (WG) as a laboratory-scale strategy to transform an NS containing cinnarizine (CN) into granules, which were intended for direct administration or to be further processed. Methods: A range of polymers, characterized by different interaction mechanisms with aqueous fluids, were employed as carriers to incorporate the CN-containing NS during manual WG. The resulting granules were thoroughly characterized before tableting. Results: The NS-loaded products exhibited satisfactory physio-technological properties, effective nanocrystal redispersibility, high drug load efficiency, and expected in vitro performance. Moreover, they turned out to be suitable intermediates for mini-tablet production. Conclusions: Based on the data collected, WG turned out to be an effective lab-scale method for transforming an aqueous CN-containing NS into solid products (i.e., granules and mini-tablets), while preserving the starting properties of the drug nanocrystals. By adjusting formulation and process parameters, a variety of release kinetics were achieved, highlighting the value of the pursued approach, especially for early-stage screening of new drug candidates belonging to class II of the biopharmaceutical classification system. Full article

Certain clayey soils are susceptible to swelling and shrinkage due to moisture variations, which can lead to ground deformation and structural damage. Although traditional stabilization methods using lime and cement are effective, they involve high energy consumption and significant CO₂ emissions. In response to sustainability concerns, this study investigates the potential of in situ geopolymer stabilization of clay soils using industrial by-products as eco-friendly binders. Experimental studies were conducted on clay specimens stabilized with geopolymer binders produced from fly ash and waste brick powder activated by alkaline solutions. The selected clay exhibited stiff to very stiff behavior and was used as a reference material to ensure reliable evaluation without the influence of severe initial degradation. Reference samples with identical water content but without alkaline activation were also prepared. The primary objective was to assess geopolymers as a sustainable alternative to conventional binders, focusing on moisture sensitivity and long-term mechanical performance. Laboratory strength tests demonstrated that geopolymer-treated specimens exhibited significantly higher strength compared to untreated samples, indicating substantial improvement in engineering properties. Furthermore, Scanning Electron Microscopy (SEM) analyses revealed that the combination of dual activators (NS+NH) and thermal curing at 85 °C transformed the weak clay matrix into a dense, fibrous geopolymer network. However, the high curing temperature was primarily used to study the reaction mechanisms; the practical applicability of the method should be evaluated based on results obtained at ambient temperature. This structure enhanced particle bonding and mechanical interlocking by filling voids within the matrix. Overall, the findings confirm that geopolymer stabilization using industrial waste materials is an effective and environmentally sustainable alternative to conventional soil stabilization techniques, contributing to reduced carbon emissions in geotechnical engineering. Full article