Search Results (12,961)

Efficient interaction between PHP (Hypertext Preprocessor) applications and MySQL databases is essential for the performance of modern web systems. This study systematically compares the two most widely used PHP APIs for working with MySQL databases—MySQLi (MySQL Improved extension) and PDO (PHP Data Objects)—under identical experimental conditions. The analysis covers execution time, memory consumption, and the stability and variability of results across different types of SQL (Structured Query Language) queries (simple queries, complex JOIN, GROUP BY/HAVING). A specialized benchmarking tool was developed to collect detailed metrics over several hundred repetitions and to enable graphical and statistical evaluation. Across the full benchmark suite, MySQLi exhibits the lowest mean wall-clock execution time on average (≈15% overall). However, under higher query complexity and in certain connection-handling regimes, PDO prepared statement modes provide competitive latency with improved predictability. These results should be interpreted as context-aware rankings for the tested single-host environment and workload design, and as a reusable benchmarking framework intended for replication under alternative deployment models. Statistical analysis (Kruskal–Wallis and Mann–Whitney tests) confirms significant differences between the methods, while Box-plots and histograms visualize deviations and the presence of outliers. Unlike earlier studies, this work provides a controlled and replicable benchmarking environment that tests both MySQLi and PDO across multiple API modes and isolates the impact of native versus emulated prepared statements. It also evaluates performance under complex-query workloads that reflect typical reporting and analytics patterns on the ClassicModels schema. To our knowledge, no previous study has analyzed these factors jointly or provided a reusable tool enabling transparent comparison across PHP–MySQL access layers. The findings provide empirical evidence and practical guidelines for choosing the optimal API depending on the application scenario, as well as a tool that can be applied for further testing in various web environments. Full article

Sequential twin-tunnel excavation has become increasingly common as urban rail networks expand, making both deformation control and construction-phase carbon management essential for sustainable underground development. This study investigates the spatiotemporal development of ground settlement induced by parallel Earth Pressure Balance shield tunnelling in a twin-tunnel section of the Hangzhou Metro, based on long-term field monitoring. The settlement process is divided into three stages—immediate construction settlement, time-dependent additional settlement, and long-term consolidation—each associated with distinct levels of energy input, grouting demand, and embodied-carbon release. Peck’s Gaussian function is used to model transverse settlement troughs, and Gaussian superposition is applied to separate the contributions of the leading and trailing tunnels. The results indicate that the trailing shield induces ahead-of-face settlement at approximately two excavation diameters and produces a deeper–narrower settlement trough due to cumulative disturbance within the overlapping interaction zone. A ratio-type indicator, the Twin-Tunnel Interaction Ratio (TIR), is proposed to quantify disturbance intensity and reveal its environmental implications. High TIR values correspond to amplified ground response, prolonged stabilization, repeated compensation grouting, and increased embodied carbon during construction. Reducing effective TIR through coordinated optimization of shield attitude, face pressure, and grouting parameters can improve both deformation control and carbon efficiency. The proposed framework links geotechnical behaviour with environmental performance and provides a practical basis for risk-controlled, energy-efficient, and low-carbon management of sequential shield tunnelling. Full article

Background/Objectives: The poor aqueous solubility of curcumin (CUR) limits its pharmaceutical application. Although amorphization can enhance its solubility, the amorphous form often exhibits insufficient physical stability. Co-amorphization, particularly drug–drug co-amorphous (CAM) formation, offers a promising approach to improve solubility, stability, and therapeutic efficacy. This study aimed to prepare and evaluate two CUR-based CAM systems using isoquinoline alkaloids berberine hydrochloride (BER) and palmatine hydrochloride (PAL) as co-formers to achieve simultaneous stabilization and synergistic bioactivity. Methods: CUR-BER and CUR-PAL CAM systems were prepared via rotary evaporation under vacuum at a 1:1 molar ratio. The solid-state properties were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscope (SEM), and ¹³C solid-state nuclear magnetic resonance spectroscopy (ssNMR). Dissolution, solubility, and stability studies were conducted, while antioxidant and anticancer activities were assessed by DPPH/ABTS⁺ radical-scavenging and MTT assays using HT-29 colorectal cancer cells. Results: PXRD and DSC confirmed the formation of single-phase amorphous systems with higher glass transition temperatures, indicating strong intermolecular interactions between CUR and BER/PAL. ¹³C ssNMR spectroscopy evidenced hydrogen-bond formation between the enolic hydroxyl moiety of CUR and the methoxy oxygen atoms in BER or PAL molecules. Both CAM systems significantly enhanced the solubility and dissolution rate of CUR, with CUR-PAL CAM showing up to a 15.1-fold solubility improvement. The CAM systems also displayed superior thermal stability, photolytic stability, and improved short-term humidity resistance, together with enhanced antioxidant and anticancer activities compared with pure amorphous CUR. Conclusions: Co-amorphization of CUR with isoquinoline alkaloids effectively improved solubility, stability, antioxidant and anticancer activities, representing a promising strategy for the rational design of multifunctional amorphous CUR-based drug formulations. Full article

This study evaluated the formulation and stability of a quadrivalent glycoconjugate Shigella vaccine candidate based on four predominant strains (S. flexneri; 2a, 3a, and 6, and S. sonnei) covering ~64% of global Shigella infections. Each glycoconjugate antigen consists of a strain-specific O-polysaccharide (O-PS) covalently linked to the carrier protein IpaB, a component of the Shigella type III secretion system. First, selective competitive ELISAs were developed to measure antigenicity of the four O-PS-IpaB conjugates formulated with different adjuvants (i.e., Alhydrogel^®, AH; Adju-phos^®, AP; and CpG-1018^®, CpG). Next, the monovalent S. sonnei O-PS-IpaB conjugate was studied to elucidate interactions with aluminum salt adjuvants (AH, AP) under different solution conditions. Third, the stability profiles of AH- or AP-adjuvanted S. sonnei O-PS-IpaB conjugate in various formulations (±CpG) were determined at different temperatures. Interestingly, incubation at 25 °C for 2 weeks resulted in increased antigenicity values when the antigen was bound to AP or AH, suggesting increased epitope exposure upon adjuvant binding. When bound to AP adjuvant at pH 5.8, the best glycoconjugate antigen stability was observed at elevated temperatures. The CpG adjuvant under these conditions, however, displayed incompatibility (i.e., material loss), presumably from precipitation due to lack of interaction with AP and presence of the detergent LDAO from the bulk antigen buffer. In contrast, the glycoconjugate antigen and CpG adjuvant were both bound to the AH adjuvant and stable at 2–8 °C, pH 7.0. This AH-CpG formulation of the O-PS-IpaB conjugate antigens was identified as a promising candidate for future animal immunogenicity testing. Full article

Subglacial topography is a critical boundary condition for ice sheet models projecting past and future ice sheet–climate interactions. Contemporary ice-sheet-wide bed topography datasets are partially derived using mass conservation, but approximately 75% of the most widely used Greenland Ice Sheet (GrIS) dataset is based on simple interpolation of airborne radio-echo sounding (RES) measurements, such as kriging or streamline diffusion. Due to limited independent validation data, the errors and biases in this approach are poorly understood, creating largely unknown uncertainties in subglacial topography. Here, we interpolated synthetic RES observations of bed topography over ice-free areas with a known topography at a 5 m spatial resolution and quantify discrepancies. We found that the absolute error in kriged bed topography increases with distance from the input data, though at a reduced rate than previously estimated. The difference between an interpolated elevation estimate and the local mean elevation is a strong predictor of real bed errors (R² = 0.72), with further improvement as input observation sparsity increases (R² > 0.82). We propose a method to quantify and reduce uncertainty in kriged bed topography in sparsely surveyed regions, reducing uncertainty for at least 56% of the kriged interior at a 99% confidence interval. Our results suggest that subglacial depth is on average 5 m deeper than previous estimates, though individual areas may be shallower or deeper (σ = 41 m). Consequently, the area grounded below sea level is likely underestimated by 2%, increasing to 29% for regions deeper than 200 m. These findings have potential implications for the future stability of the GrIS under climate change. Full article

Live imaging has been instrumental in understanding cellular dynamics in Drosophila tissues, but technical limitations have prevented the long-term visualization of cell competition in adult brains. Here, we describe a simple ex vivo protocol that enables extended live imaging of adult Drosophila brains for up to 32 h. The method relies on non-supplemented Schneider’s Drosophila medium and hydrophobic interactions to maintain brain stability during imaging, eliminating the need for complex culture conditions or embedding procedures. We validate this approach by studying cell competition in the optic lobes following traumatic brain injury, where cell competition is expected to occur with a peak at 48 h after damage. We demonstrate the value of this method by visualizing the expression of the fitness checkpoint Azot in a loser cell and its subsequent elimination. This protocol offers a versatile platform for studying cell competition and other cellular processes requiring extended observation of the adult Drosophila brain. Full article

Soil microbial communities are fundamental to ecosystem function and soil health, yet how differing land-use intensities shape these communities and their interaction networks remains unclear. We investigated soils from greenhouse cultivation (GH), arched shed systems (ASs), and open farmlands (FLs) to compare microbial composition, diversity, and network stability under contrasting management intensities. GH soils had the highest electrical conductivity, ca. ~3.9 times higher than FL soil and ~1.9 times higher than AS soil, alongside elevated soil organic matter, total N, and available nutrients. AS soil maintained intermediate nutrient levels. Bacterial α-diversity was higher in AS and GH soils than in FL soil, whereas fungal α-diversity was comparable among systems despite differences in community composition. Microbial co-occurrence network analysis revealed the most complex and robust network in ASs, followed by FLs, while GH soil had the simplest and least stable network. Structural equation modeling showed that soil chemical properties had the largest direct influence on network complexity and stability, followed by soil enzyme activities; microbial diversity and key taxa also contributed to network complexity and stability. Overall, the moderately managed AS was superior to GH and FLs in sustaining a diverse and resilient soil microbiome and network. These findings provided actionable knowledge for optimizing land management to maintain soil ecological function. Full article

γ-Aminobutyric acid type A receptors (GABA_ARs) are pentameric ligand-gated ion channels mediating fast inhibitory neurotransmission in the mammalian brain. Although recent structural and kinetic studies have advanced understandings regarding their activation mechanisms, the molecular determinants coupling agonist binding to channel gating remain unclear. We investigated the contribution of the β₂E153 residue, located on loop B of the extracellular domain, to the activation of α₁β₂γ₂ GABA_ARs. Macroscopic and single-channel patch clamp recordings were used to characterize two β₂E153-mutants: charge reversal (β₂E153K) and hydrophobic substitution (β₂E153A). Both substitutions disrupted normal receptor kinetics, with β₂E153K selectively accelerating deactivation and β₂E153A affecting both deactivation and desensitization. Single-channel analysis showed that β₂E153A reduced open probability and mean open times, consistent with altered gating transitions inferred from kinetic modeling. Structural inspection suggested that β₂E153 forms electrostatic interactions with β₂K196 and β₂R207 to stabilize loop C and maintain the agonist-bound conformation. The disruption of this interaction likely destabilizes loop C, leading to weakened agonist binding and modified gating. Overall, our results identify β₂E153 as a key element in the long-range allosteric network linking the binding site to the channel gate in GABA_ARs. Full article

Understanding how urbanisation shapes species distributions and ecological interactions requires long-term, spatially structured data. Using an exceptionally rare 40-year dataset (1986–2025) from 150 habitat patches and 102 downtown grid cells in St. Petersburg, Russia, we examined patterns in birch (Betula pendula and B. pubescens) persistence, ground conditions, woody vegetation, and the occurrence of Eriocrania leaf-mining moths. Birch presence, birch abundance, and ground quality declined both toward the city centre and over time, whereas woody plant cover showed no clear spatial or temporal pattern. Eriocrania occurrence within birch-containing patches was influenced primarily by habitat type, artificial ground, and birch abundance, while distance to the city centre, year, and woody cover exerted no consistent effects. Habitat characteristics offered only moderate predictive power for local extinction risk in both birches and Eriocrania, indicating that multiple drivers interact to shape patch dynamics. Contrary to the widespread declines observed in many insect taxa, Eriocrania populations exhibited no directional density trend across four decades. This long-term stability highlights the resilience of specialised herbivores in heterogeneous urban landscapes and underscores the value of extended temporal datasets for detecting subtle or unexpected ecological responses to urbanisation. Full article

We present a comprehensive mathematical analysis of a within-host dual-target HIV dynamics model, which explicitly incorporates the virus’s interactions with its two primary cellular targets: CD4${}^{+}$ T cells and macrophages. The model is formulated as a system of five nonlinear delay differential equations, integrating three distinct discrete time delays to account for critical intracellular processes such as the development of productively infected cells and the maturation of new virions. We first establish the model’s biological well-posedness by proving the non-negativity and boundedness of solutions, ensuring all trajectories remain within a feasible region. The basic reproduction number, ${\mathcal{R}}_0^d$, is derived using the next-generation matrix method and serves as a sharp threshold for disease dynamics. Analytical results demonstrate that the infection-free equilibrium is globally asymptotically stable (GAS) when ${\mathcal{R}}_0^d\le 1$, guaranteeing viral eradication from any initial state. Conversely, when ${\mathcal{R}}_0^d>1$, a unique endemic equilibrium emerges and is proven to be GAS, representing a state of chronic infection. These global stability properties are rigorously established for both the non-delayed and delayed systems using carefully constructed Lyapunov functions and functionals, coupled with LaSalle’s invariance principle. A sensitivity analysis identifies viral production rates ($p_1,p_2$) and infection rates (${\beta }_1,{\beta }_2$) as the most influential parameters on ${\mathcal{R}}_0^d$, while the viral clearance rate (m) and maturation delay (${\tau }_3$) have a suppressive effect. The model is extended to evaluate antiretroviral therapy (ART), revealing a critical treatment efficacy threshold ${ϵ}^{cr}$ required to suppress the virus. Numerical simulations validate all theoretical findings and further investigate the dynamics under varying treatment efficacies and maturation delays, highlighting how these factors can shift the system from persistence to clearance. This study provides a rigorous mathematical framework for understanding HIV dynamics, with actionable insights for designing targeted treatment protocols aimed at achieving viral suppression. Full article

Background: Insomnia is prevalent and difficult to treat safely over the long term. Given the role of the microbiota–gut–brain axis in melatonin and hypothalamic–pituitary–adrenal (HPA) regulation, and preclinical evidence for Limosilactobacillus fermentum PS150, we evaluated whether a heat-treated formulation (HT-PS150) could improve sleep and modulate endocrine/circadian markers in adults with poor sleep. Methods: In a randomized, double-blind, placebo-controlled trial, 84 adults aged 20–60 years with PSQI ≥ 5 and ISI < 22 were assigned to receive either placebo or HT-PS150 for eight weeks. Outcomes included patient-reported sleep (PSQI, ISI), anxiety/depression (GAD-7, PHQ-9), quality of life (QLESQ-SF), gastrointestinal symptoms (VAS-GI), wrist actigraphy (Fitbit Inspire 3), and sleep-relevant biomarkers measured from urine, saliva, and/or blood samples (melatonin, cortisol, orexin, serotonin, GABA, and/or norepinephrine). Repeated measures were analyzed using generalized estimating equations. An exploratory proportional regulation analysis classified individual biomarker changes as up- or down-regulated and compared proportions between study arms. Per-protocol analyses required ≥80% compliance. Results: Improvements in the primary outcomes, PSQI and ISI, were observed over time in both groups, while no significant group × time interactions were detected. In exploratory proportional analyses, a higher proportion of participants in the HT-PS150 group exhibited up-regulated nocturnal melatonin secretion and improved daytime plasma orexin levels, as well as a tendency toward greater reductions in nocturnal salivary cortisol compared with placebo. In subgroup analyses with higher baseline insomnia severity (ISI ≥ 8), HT-PS150 was associated with greater improvements in PSQI (notably sleep duration and efficiency) and reduction in anxiety (GAD-7) upon post hoc testing. Conclusions: Although group mean scores on sleep symptom scales did not differ significantly in the full cohort, HT-PS150 appeared to modulate sleep–wake regulation by enhancing nocturnal melatonin secretion, attenuating HPA-axis activity, and stabilizing wakefulness. Clinical benefits were most evident among participants with greater baseline symptom burden, suggesting potential utility in more symptomatic populations. Full article

The limited availability of competent foundation soils in rapidly urbanizing regions makes construction on weak clayey deposits increasingly unavoidable. Such soils typically exhibit low shear strength, high compressibility, and pronounced deformation under undrained conditions, posing significant risks to structural safety and long-term serviceability. In this study, the effect of basalt fiber inclusion on the undrained shear behavior of clay soil obtained from the Kızılyer region of Eskişehir, Türkiye, was experimentally investigated using a ring shear apparatus. Initially, soil classification and index property tests were performed to characterize the material. Subsequently, clay specimens were reinforced with varying basalt fiber contents and subjected to large-strain shearing conditions. The evolution of peak and residual shear strength with increasing fiber dosage was systematically evaluated. The results indicate that basalt fiber reinforcement leads to a substantial enhancement in both peak and residual shear strength and contributes to improved post-peak ductility. The observed improvements are primarily attributed to fiber–soil interaction mechanisms, including tensile bridging and crack-arrest effects, which modify the failure process and delay shear localization. Overall, the findings demonstrate that basalt fiber represents an environmentally compatible and mechanically effective alternative for sustainable soil improvement applications, particularly in clayey soils subjected to undrained loading conditions. Full article

Background/Objective: Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β plaques, derived from the amyloid precursor protein through sequential cleavage by β-secretase 1 (BACE-1) and γ-secretase. BACE-1 is therefore a key drug target for designing of selective inhibitors to avoid off-target effects associated with BACE-2 inhibition. The objective of this study was to design novel BACE-1 inhibitors using a structure-based drug design approach. Methods: A focused compound library was designed based on the SAR of N-(4-fluorophenyl)formamide derivatives. In silico ADME predictions were performed to assess pharmacokinetic suitability. Compounds showing favorable ADME profiles were subjected to molecular docking against the BACE-1 enzyme. The top-scoring hit, compound 9.7 (−5.48 (kcal/mol), was further evaluated using a 200 ns MD simulation to assess the stability of its binding interactions with BACE-1. Results: Designed compounds indicated acceptable physicochemical and ADME characteristics. Molecular docking identified compound 9.7 as exhibiting favorable binding interactions with binding pocket residues of BACE-1. The 200 ns MD simulation further confirmed the stability of the docked complex. MD simulations confirmed that 9.7 forms stable interactions with the catalytic residue ASP32 and key hydrophobic residues TRP115 and PHE108 of BACE-1. These important interactions are absent in the reference compound verubecestat. Conclusions: The multi-step computational analysis suggests that compound 9.7 is a promising and selective BACE-1 inhibitor. Its favorable ADME profile, favorable docking interactions, and stable MD simulation behavior highlight its potential as a hit compound for further optimization in the development of anti-Alzheimer’s agents. Full article

Hybrid AC/DC transmission expansion planning must balance investment cost, supply reliability and AC/DC stability, which challenges conventional mathematical programming and heuristic methods. This paper proposes a multi-objective planning framework based on an improved multi-step backtracking α-Q(λ) reinforcement learning algorithm with eligibility traces and an adaptive learning factor. A tri-objective model minimises annual economic cost, expected power shortage and a comprehensive electrical index that combines electrical betweenness, commutation-failure margin and effective short-circuit ratio. The mixed-integer planning problem is reformulated as an interactive learning process, where the state encodes candidate line construction decisions, the action builds or cancels lines, and the eligibility-trace matrix is used to quantify line importance. Case studies on the Garver-6 system, the IEEE 24-bus reliability test system and a 500 kV regional hybrid AC/DC grid show that, compared with classical Q-learning, the proposed method yields lower annual cost, reduced expected power shortage and improved AC/DC stability; in the 500 kV system, the expected annual power shortage is reduced from 70,810 MWh to 28,320 MWh. Full article

Lycopene is a potent antioxidant carotenoid with significant health-promoting properties. However, its practical application is limited by poor water solubility. This study aimed to enhance lycopene dispersibility through the development of solid dispersions obtained by hot-melt extrusion (HME). Polymeric carriers composed of polyvinylpyrrolidone K30 (PVP K30), phosphatidylcholine, and xylitol were designed to achieve optimal processing conditions and thermal stability. Nine formulations containing 10–30% lycopene were prepared and characterized using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FT-IR), and dispersibility testing. TGA confirmed the thermal stability of lycopene at the extrusion temperature (150 °C). DSC and XRPD analyses indicated partial amorphization of lycopene in the extrudates, while FT-IR spectra revealed molecular interactions between lycopene and carrier components, particularly hydroxyl and carbonyl groups. Among the tested systems, the formulation containing PVP K30 and xylitol without phosphatidylcholine exhibited the highest dispersibility (1.0484 mg/mL after 3 h). Dispersibility decreased with increasing lycopene content. These findings demonstrate that HME is an effective technique for producing partially amorphous lycopene dispersions with improved dispersibility, and that polymer–polyol systems are particularly promising carriers for enhancing lycopene bioavailability. Full article