Search Results (3,757)

The ATP-binding cassette transport protein Pdr5p is known to play a role in multidrug resistance in Saccharomyces cerevisiae by effluxing structurally diverse xenobiotics; yet the physicochemical determinants of substrate recognition remain poorly defined. To address this, density functional theory (DFT) calculations at the B3LYP-D3BJ/def2-SVP level were combined with machine learning to derive a predictive model of substrate recognition using a curated dataset of 66 compounds spanning 9 functional categories. A hybrid support vector machine (SVM) classifier achieved 96.3% accuracy (95% CI: 81.0–99.9%, Clopper–Pearson exact) in discriminating substrates from non-substrates under leave-one-out cross-validation. Feature importance analysis identified lipophilicity (LogP, F-score = 37.5) as the dominant descriptor, suggesting that membrane partitioning constitutes the initial recognition step. The HOMO–LUMO gap contributed secondarily (F-score = 12.4). Substrates were further distinguished by high frontier orbital focalization, with frontier orbital spread of 1.8–2.6%, compared to 4.18–7.22% for non-substrates. Notably, a model trained exclusively on Pdr5p data achieved 87% prediction accuracy when applied without retraining to the human P-glycoprotein (ABCB1) dataset, suggesting conserved physicochemical principles of substrate recognition across evolutionarily distant ABC transporters. These findings provide a quantum chemical framework for understanding and potentially predicting MDR transporter substrate specificity. Full article

Superradiance is a scattering process in which incident waves are amplified by a scatterer, such as a black hole, leading to the extraction of energy from the system. In this work, we study superradiant scattering within Bopp–Podolsky electrodynamics, an extension of Maxwell electrodynamics that introduces higher-derivative terms in the electromagnetic field and a non-minimal coupling to curved spacetime. We analyze the propagation of scalar waves in a static, spherically symmetric wormhole geometry obtained perturbatively from the Reissner–Nordström solution of General Relativity coupled to Maxwell electrodynamics. We demonstrate that superradiant scattering occurs in this background and, through numerical analysis, find that the Podolsky parameter suppresses the amplification. Full article

Complex networks have become a fundamental paradigm for modeling real-world systems. Synchronization of such networks, particularly under hyperchaotic dynamics, presents a significant control challenge due to the high-dimensional state space and multiple positive Lyapunov exponents. This paper addresses the driver node selection problem in a 4D Hyperchaotic Lorenz complex network, formulating it as a constrained binary optimization task. We evaluate a pool of advanced metaheuristics, including the quantum genetic algorithm (QGA), seahorse optimizer (SHO), and artificial bee colony (ABC), across multiple network experiments conducted over 30 independent runs to guarantee statistical validity. The performance of these solvers is rigorously benchmarked against traditional topological heuristics, a random selection baseline comprising 600 feasible configurations, and verified through Wilcoxon statistical testing. Furthermore, addressing computational sustainability, we introduce a “Green-Artificial Intelligence” architecture based on dual-tier structured query language memoization (SQL-memoization) and provide a detailed runtime comparison evaluating its efficiency. The empirical results indicate that swarm-intelligence methods such as ABC and SHO exhibit robust competitive performance in minimizing synchronization errors while the Green-AI framework consistently and drastically reduces the computation of the repetitive simulations. Full article

Malassezia are commensal lipid dependent yeasts which can cause opportunistic skin infection. Topical imidazole antifungals such as clotrimazole and ketoconazole are the frontline treatment. However, the tendency of fungal infections to recur, combined with the emergence of multi-azole-resistant Malassezia isolates means that many patients have used these antifungal treatments repeatedly or for extended durations with limited efficacy. While the impact of single azole treatments has been studied, the ability of specific azoles to induce cross-resistance is unclear. Understanding the effect of prior exposure of one treatment on susceptibility to other antifungals is important in the selection of the appropriate treatment to avoid driving the evolution of greater resistance. We previously identified drug transporters from the ATP-Binding Cassette (ABC) and Major Facilitator Superfamily (MFS) to be upregulated on extended exposure to clotrimazole. In this study, we investigated the effect of extended clotrimazole, ketoconazole and fluconazole exposure on antifungal cross-resistance profiles and examined the expression of the MFS transporters OPT1 and FLR1 in resistance emergence. We observed that treatment with clotrimazole was associated with increased cross-resistance to other antifungals. Ketoconazole treatment caused elevated MICs in all tested antifungals that did not decrease after drug removal. These findings advance our understanding of fungal adaptive resistance mechanisms and inform improved antifungal strategies to mitigate resistance development. Full article

This study reports the plant-mediated synthesis of copper-oxide-decorated magnetic iron oxide composite (CuO@Fe₃O₄) nanoparticles using Dolomiaea costus extract and their application as nanocarriers for β-galactosidase immobilization. The fabricated nanocomposite exhibited favorable physicochemical properties, achieving an immobilization efficiency of 83%, with enhanced thermal and pH tolerance compared to the free enzyme. Kinetic analysis revealed a modest increase in Km and a 31% decrease in Vmax after immobilization, while maintaining 69% of the catalytic activity, confirming the system’s suitability for industrial lactose hydrolysis. Reusability and storage tests showed 79% retained activity after five cycles and 77% after 60 days at 4 °C. In milk hydrolysis, the immobilized enzyme achieved 77% conversion within 3 h, following pseudo-first-order kinetics. Biocompatibility was evaluated using HepG2 cells via the MTT assay. BDH, MDH, and ABC maintained high cell viability across the tested dilution range of 25–100% (v/v), indicating no detectable cytotoxic effect under the experimental conditions, whereas cisplatin showed marked cytotoxicity with an IC₅₀ of 14.98 µg/mL. These findings demonstrate that the green-synthesized CuO@Fe₃O₄ support provides a safe, reusable, and magnetically recoverable platform for β-galactosidase immobilization, offering a promising sustainable strategy for producing lactose-free dairy products. Full article

Microsporum canis is a globally prevalent zoonotic dermatophyte and the major causative agent of dermatophytosis in both pets and humans. The widespread clinical use of antifungal drugs has led to the frequent emergence of decreased susceptibility, while its molecular features and the genomic basis of cross-host transmission remain incompletely elucidated. In this study, 38 clinical M. canis isolates were collected from dogs and cats in Beijing (2025). We determined the minimum inhibitory concentrations (MICs) of six common antifungal agents via microbroth dilution, and performed whole-genome sequencing and comparative genomic analysis. All isolates showed high clonal homogeneity, with ANI $>99.9\%$ to the reference. A local human-derived strain was nested within the pet-derived clade, supporting zoonotic cross-host transmission. Terbinafine exhibited the highest activity, while itraconazole, voriconazole, posaconazole, griseofulvin, and ciclopirox olamine showed higher MICs; 11 isolates showed a multidrug high-MIC phenotype. Notably, copy number variation in the ABC transporter gene CDR1 was positively correlated with MICs of multiple antifungal agents ($p<0.05$). This study provides a genomic basis for optimized antifungal therapy, resistance surveillance and transmission control of zoonotic M. canis. Full article

Fat deposition in laying hens involves lipid synthesis, transport, storage, and allocation across multiple tissues, yet the metabolic links between abdominal fat (AF) and egg yolk (EY) lipid deposition remain unclear. Here, we integrated whole-genome resequencing data with untargeted metabolomic profiles from the liver, duodenum, ileum, cecum, and serum of 248 purebred Rhode Island Red hens at 100 weeks of age. We estimated metabolite-explained variance (me²) for 22 fat deposition-related traits, evaluated metabolite heritability, and combined Spearman correlation analysis with bidirectional generalized summary-data-based Mendelian randomization (GSMR) to identify shared metabolites and pathways associated with AF and EY traits. The me² showed clear tissue specificity, with the liver, serum, and duodenum showing significant explanatory signals for 77.3% (17/22), 72.7% (16/22), and 68.2% (15/22) of fat-related traits. Liver-, AF-, and body weight-related traits showed stronger metabolomic explanatory signals, with significant proportions of 71.4–100.0%, 28.6–100.0%, and 100.0% across tissues, respectively, whereas EY-related traits showed more restricted and tissue-specific associations (0–33.3%). Correlation analysis identified liver-enriched AF–EY shared metabolites (e.g., NADPH, cholesteryl sulfate, N6,N6,N6-trimethyllysine), most of which showed opposite association patterns between AF- and EY-related traits. Bidirectional GSMR prioritized 20 candidate metabolites with opposite putative effects on AF and EY traits, including CDP-choline, phosphorylcholine, and allantoin. Pathway integration highlighted fructose/mannose metabolism, glycerophospholipid metabolism, ABC transporters, folate/one-carbon metabolism, amino acid metabolism, and energy metabolism as core components of the AF–EY shared network. These findings reveal tissue-specific and shared metabolic bases of fat deposition and identify candidate metabolic signatures associated with lipid partitioning between abdominal fat and egg yolk in laying hens. Full article

The analysis of the time-fractional nonlinear Sharma–Tasso–Olver (STO) equation with various initial conditions has been shown in this work. Finding the appropriate approximate solution of the problems under consideration is carried out by implementing unique strategies that combine the Adomian decomposition method (ADM), and the Generalized integral transform. The proposed method computes the results as a convergent series. The main benefit of the suggested method is that it needs minimal computing effort while producing extremely accurate results. We first apply the fractional Caputo fractional derivative (CFD) and then the Atangana–Baleanu–Caputo (ABC) derivative to solve the fractional STO problem. The nonlinear wave model for harbor and coastal designs heavily relies on the wave solutions of the STO equation. Several cases of time-fractional STO equations with various initial approximations are used to illustrate the schemes under consideration. The efficiency and dependability of the methods under consideration are confirmed by executing suitable numerical simulations. We contrast our findings with those of other approaches, including the Homotopy perturbation method (HPM), and the q-Homotopy analysis Elzaki transform method (q-HAETM). Additionally, the results of using the proposed techniques at different fractional orders are analyzed, showing that their accuracy increases as the value goes from fractional order to integer order. The results gained indicate that the applied scheme is highly satisfying and investigate the complicated nonlinear problems that arise in innovation and science. Full article

This study aims to investigate the effects of cysteamine zinc supplementation on milk production, composition, amino acid profile, and metabolites in mares. Building on prior experimental findings, a dose of 7 mg/kg body weight of CS-Zn was selected for the experimental group, which was compared with a control group. Milk samples were collected at various time points, and milk yield was recorded each time. Routine analysis of milk components, as well as the determination of milk metabolites and amino acids, were performed. The results indicated that, compared to the control group, the experimental group exhibited increases in milk yield and the content of milk fat, lactose, and non-fat solids (p < 0.05), with an extremely significant increase in milk protein (p < 0.01). Conversely, the levels of L-glutamine and L-proline in milk were significantly reduced (p < 0.05). Metabolomic analysis revealed that differentially expressed metabolites were enriched in pathways such as ABC transporters, D-aminoadipate metabolism, aminoacyl-tRNA biosynthesis, and protein digestion and absorption. Notably, milk metabolites including cAMp, biotin, and taurine showed a tendency to be upregulated, while oxoglutaric acid, methionine, and diacetyloxyxanthone were downregulated. Based on evidence from the literature other species, it is speculated that CS-Zn supplementation may be associated with alterations in endocrine and amino acid metabolism pathways, potentially influencing lactation performance in mares. However, because no hormones were directly measured in this study, such a mechanism remains speculative and requires direct experimental validation. Full article

Copper (Cu) contamination in aquatic environments induces oxidative stress and structural damage to crustaceans. This study investigated the protective effects and associated mechanisms of exogenous melatonin (MT) against Cu-induced toxicity in Procambarus clarkii using integrated physiological, histopathological, proteomic, and molecular analyses. MT supplementation enhanced antioxidant defense by elevating SOD, CAT, and T-AOC activities, while reducing MDA accumulation, with peak effects observed at 24 h. MT also restored endogenous melatonin levels and regulated phosphatase activity, thereby maintaining immune and metabolic homeostasis. Histopathology showed reduced hepatopancreatic damage, characterized by reduced epithelial vacuolization and preserved basement membrane integrity. Proteomics suggested that MT modulates a multilayered network associated with detoxification, redox balance, and cellular homeostasis. Pathway enrichment showed that Cu exposure dysregulated proteins involved in mitochondrial biogenesis, ABC transporters, membrane trafficking, and apoptosis. MT administration partially counteracted these alterations and was associated with the regulation of glutathione metabolism, as well as reduced enrichment of lysosome- and apoptosis-related pathways. Quantitative RT-PCR results were consistent with the proteomic data. Overall, MT partially alleviated Cu-induced toxicity and was associated with enhanced antioxidant defense, improved cellular homeostasis, and metabolic regulation. Our study provides new molecular insights and suggests its potential application for mitigating metal toxicity in aquaculture. Full article

Background: Kidney transplant recipients (KTRs) with diabetes mellitus (DM) are at high cardiovascular risk, and heart failure (HF) is a major concern. Dapagliflozin has proven benefits in HF, but data in KTRs are scarce. Methods: Retrospective analysis of adult KTRs with DM and HF who received dapagliflozin. Data were collected at baseline, defined as dapagliflozin initiation, and at the most recent follow-up (April 2024). Outcomes included changes in LVEF, renal function, metabolic and hemodynamic parameters, hospitalizations, and adverse events. Results: In 32 KTRs (median age 60.5 years, 66% male), after a median follow-up of 2.2 years, left ventricular ejection fraction (LVEF) did not change significantly (60% to 58%, p = 0.28). Systolic BP decreased by 5 mmHg (p < 0.001) and diastolic BP by 3 mmHg (p = 0.034). HbA1c decreased from 7.3 [6.6–8.1] to 6.8 [6.3–7.7]% (p = 0.034), while LDL-c and triglycerides decreased (p = 0.013 and p < 0.001). Body weight and BMI also decreased (both p < 0.001). Renal function, as assessed by eGFR, remained stable (p = 0.633), with no major renal safety signals. No deaths, severe hypoglycemia, or ketoacidosis occurred; urinary tract infections in 12%. Conclusions: In this exploratory cohort, dapagliflozin use was followed by stable graft function and changes in metabolic and hemodynamic parameters. No significant change in LVEF was observed. Given the observational design, small sample size, limited echocardiographic data, and absence of a control group, causal inference is not possible. These hypothesis-generating findings require confirmation in prospective controlled trials of KTRs with diabetes and heart failure. Full article

Forecasting spare parts demand is challenging due to its intermittent, sparse, and highly irregular nature. Traditional inventory strategies, based on stable demand patterns, often lead to inefficiencies, including excess inventory and poor service performance. This study examines the impact of feature engineering combined with ABC–XYZ inventory segmentation on forecasting accuracy in a real-world industrial context. A biweekly forecasting framework was developed using six years (2019–2024) of transactional data from ERP and Field Service Management (FSM) systems of a forklift service company. Fifteen derived features capturing demand dynamics, intermittency, service behavior, and statistical structure were constructed and evaluated using Random Forest, XGBoost, and Support Vector Regression (SVR) models. The results show that restricting modeling to AY/BY inventory categories substantially improves predictive accuracy, reducing RMSE from >22 to <3 compared to full-SKU modeling. A reduced seven-feature set further lowers XGBoost’s RMSE to 2.51 (MAE = 2.14), achieving the best performance across all tested configurations on the 2024 hold-out period. The best-performing configuration achieves a Predicted-Demand Turnover Index (PDTI) of 44.13, compared with a baseline actual stock turnover of 2.78 (€65,944 actual demand/€23,721 historical average stock). PDTI is a theoretical scenario index; operationalizing it requires inventory-policy simulation under realistic constraints. These findings highlight that forecasting performance in intermittent-demand environments depends more on data representation and segmentation than on model selection alone. The study provides a reproducible, interpretable framework for integrating feature engineering and inventory segmentation into data-driven inventory management. Full article

Co-contamination with dibenzofuran (DBF) and cadmium (Cd(II)) poses a major challenge in environmental remediation. While Burkholderia sp. can degrade polycyclic aromatic hydrocarbons and tolerate heavy metals, the coordinated mechanism governing DBF degradation under high Cd(II) stress remains elusive. Here, we characterize Burkholderia sp. FM-2, which optimally degrades 600 mg/L DBF at pH 6.0 and 25 °C, achieving 91.8% removal within 48 h. FM-2 exhibits exceptional Cd(II) tolerance, with a minimum inhibitory concentration of 2000 mg/L. UPLC-MS/MS confirms DBF degradation via dioxygenase-mediated hydroxylation and sequential enzymatic reactions. Transcriptomics reveals, for the first time, concurrent upregulation of genes encoding RND efflux pumps, ABC transporters, P-type ATPases, and core DBF-degrading enzymes under high Cd(II) stress, enabling the synergistic maintenance of intracellular Cd(II) homeostasis and efficient DBF degradation. Collectively, FM-2 remediates DBF-Cd(II) co-contamination via coordinated transcriptional regulation of degradation and detoxification pathways, offering a promising strain resource and molecular basis for the bioremediation of co-contaminated environments. Full article

Healthcare facilities are among the most energy-intensive public infrastructures due to their continuous operations, complex systems, and critical service requirements. In this context, Energy Performance Contracts (EPCs) have gained increasing attention as a strategic tool for enhancing energy efficiency and sustainability in healthcare facilities. This paper investigates the potential and implementation of EPCs in the hospital sector, with a particular focus on their integration within Public–Private Partnership (PPP) frameworks. The study addresses that gap through a cross-case analysis of fourteen hospital EPC projects implemented in Italy, the United Kingdom, the Nordic countries and Central-Eastern Europe, mapping their technical scope against a three-family taxonomy (envelope, plant systems, regulation and monitoring) and benchmarking their energy and economic performance. All figures reported derive from project documentation and contractual monitoring records. The results show that envelope-led configurations deliver the deepest reductions in primary and final energy consumption (up to 50% on the baseline), while plant-side measures, and trigeneration in particular, generate the largest absolute CO₂ savings (from approximately 500 to 17,000 tCO₂eq/yr); lighting, and building management systems (BMS) retrofits, although ubiquitous, account for a 20–25% band when deployed in isolation. The findings reframe EPCs as a configurable contract for decarbonization in healthcare environments and offer practitioners a reading grid for scoping future hospital retrofits under this framework. Full article

In this paper, we study some existence and stability results related to the boundary value problem involving the Atangana–Baleanu–Caputo hybrid fractional derivative. More precisely, we transform the studied problem to an equivalent integral equation, and after that, by applying appropriate fixed-point theorems and using suitable conditions, we prove the existence of solutions. Furthermore, we derive sufficient conditions that guarantee the stability in the sense of Hyers–Ulam. To support the theoretical findings, we present illustrative examples along with numerical simulations. Full article