Search Results (645)

Brown macroalgae are a promising substrate for alginate production, yet the conventional acid–alkali route raises environmental and quality concerns due to its high reagent inventory, large saline effluents, and partial depolymerization of the polymer backbone. To address these limitations, we evaluated five extraction strategies on a single Saccharina latissima feedstock: conventional acid–alkali extraction as the reference, enzymatic hydrolysis (HE), extrusion combined with enzymatic hydrolysis (Ex-HE), sonication combined with enzymatic hydrolysis (S-HE), and the sequential combination of extrusion, sonication, and enzymatic hydrolysis (Ex-S-HE). The optimized HE process achieved an alginate yield of 34.08% on dry biomass. This value exceeds the conventional benchmark of 31.08%. Hydrolysis time and biomass loading governed the yield. Enzyme dose showed no significant effect within the studied range. Sonication alone yielded 14.55% under surface-limited kinetics, driven exclusively by acoustic amplitude. Scale-up of HE to a 150 L pilot bioreactor recovered 43% of total soluble solids through lyophilization. Ethanol precipitation at the 5 L scale delivered 26.87% of purified alginate. The two metrics describe distinct end products. They represent complementary outputs of a cascade biorefinery rather than competing routes. The HE-derived alginate matches commercial standards by FTIR, TGA, and viscosity. Its M/G ratio is expected to fall within the published range for S. latissima alginate (1.4 to 1.8). Ethanol precipitation of brown algal hydrolysates typically yields products with 80 to 95% uronic acid content. Quantitative techno-economic and environmental analysis indicates substantial reductions in CO₂-equivalent emissions and E-factor relative to the conventional route. Total cost becomes competitive when the cascade biorefinery is monetized through co-products such as mannitol, laminarin, and phlorotannins. These results position enzymatic hydrolysis as the most effective single-step strategy for alginate recovery from S. latissima. To our knowledge, this is the first study to couple face-centred central composite optimization of two pretreatment families on a single S. latissima biomass batch with a 30-fold pilot-scale validation from 5 L to 150 L and a comparative functional characterization of two recovery methods (ethanol precipitation and lyophilization). Full article

Background/Objectives: Zastaprazan (JP-1366) is a novel potassium-competitive acid blocker (P-CAB) used for the treatment of gastroesophageal reflux disease (GERD). To date, its metabolic pathways and metabolism-related drug–drug interactions (DDIs) in humans remain incompletely elucidated. This study aimed to determine the relative contributions (f_m) of cytochrome P450 isoforms to JP-1366 elimination and assess its DDI potential. Methods/Results: In vitro metabolic studies using human liver microsomes (HLMs) revealed that JP-1366 was first metabolized to M1, which subsequently underwent further oxidation, glucuronidation, and N-dealkylation. Mono-oxidation was estimated to contribute more than 46% to the overall metabolic clearance of JP-1366. Reaction phenotyping identified CYP3A as the major enzyme (f_m = 96.1%), followed by CYP1A2 (1.49%) and CYP2C9 (2.41%). By integrating in vitro data, clinical pharmacokinetic data and clarithromycin coadministration DDI data, a physiologically based pharmacokinetic (PBPK) model was developed and validated. Simulations predicted significant DDIs with strong CYP3A inhibitor (ketoconazole), with AUC ratios of 3.80. Moderate inhibitors (fluconazole and fluvoxamine) caused mild increases (AUC ratios: 1.14–1.74). Conversely, strong and moderate CYP3A inducers, rifampicin and efavirenz, produced pronounced DDIs, with AUC ratios of 0.22 and 0.50, respectively. Furthermore, simulations predicted that although JP-1366 functions as a CYP enzyme inhibitor, it would not cause clinically meaningful changes in the plasma exposure of corresponding CYP substrate drugs; however, potential interactions with CYP3A substrates still warranted consideration. Conclusions: JP-1366 is predominantly cleared via a CYP3A-dominated metabolic pathway. The PBPK simulations suggest that JP-1366 may be a moderately sensitive CYP3A substrate and a moderate inhibitor of sensitive CYP3A substrates, while its perpetrator DDI risk toward other major CYP pathways appears limited. These findings support caution or monitoring when JP-1366 is co-administered with strong CYP3A modulators or sensitive CYP3A substrates. Full article

A recent genome-wide association study showed that the protease proprotein convertase subtilisin/kexin type 6 (PCSK6) is highly expressed in idiopathic pulmonary fibrosis (IPF) lung parenchyma and that its expression is associated with disease progression and worse survival. However, whether PCSK6 plays a role in IPF pathophysiology remains elusive. This study aimed to determine whether PCSK6 contributes to IPF pathophysiology, specifically in the cross-talk between epithelial cells and fibroblasts. A549 epithelial cells were transduced with a PCSK6-GFP or control-mCherry vector. Both proliferation (crystal violet) and cell competition assays showed that PCSK6 promoted cell proliferation. Western blot and PCSK-specific fluorogenic substrate assays showed that A549-PCSK6 conditioned medium (CM) had higher PCSK6 enzyme activity compared to mCherry control A549 CM. Human lung fibroblasts stimulated with PCSK6-CM significantly decreased collagen I protein levels as compared to fibroblasts stimulated with control A549-CM. Matrix-metalloproteinase (MMP) specific fluorogenic substrate assays subsequently showed that A549-PCSK6 CM contained higher MMP activity and that PCSK6 inhibition reduced MMP activity in A549-PCSK6 CM, suggesting that PCSK6 plays a role in the activation of MMPs that may degrade collagen type I. In conclusion, epithelial PCSK6 promotes cell proliferation and decreases collagen deposition by fibroblasts, potentially via MMP activation. These in vitro data suggest that PCSK6 could play a dual role in IPF progression and its actual role in IPF should consequently be elucidated using in vivo/ex vivo models. Full article

In this study, we investigated how substrate moisture content affects the growth performance and adaptive responses of Myriophyllum aquaticum. Through a controlled simulation experiment, we systematically analyzed the morphological characteristics and physiological responses of plants under five moisture levels: 0–15%, 15–30%, 30–45%, 45–60%, and 60–75%. The results indicate that optimal growth of M. aquaticum occurred at a substrate moisture content of 60–75%, with significant increases in plant height, branching ability, and biomass. A drought acclimation response was triggered at moisture levels ≤45%, characterized by shortened root length, increased total senescent internode length, biomass allocation shift toward aboveground parts, decreased chlorophyll a content, and elevated accumulation of malondialdehyde. Plants died at moisture levels ≤15%. However, they survived at 15–30% moisture, although their biomass continued to decline. A key finding was that under conditions where the sediment surface lacked water but the substrate moisture remained at 60–75%, plants achieved efficient water utilization and canopy reconstruction through rapid root extension and stem node proliferation, and the relative growth rate was significantly higher than that of the drought group (≤45% moisture). This strong adaptive capacity under specific water conditions, combined with its dehydration tolerance, suggests that M. aquaticum could potentially have a competitive advantage over native submerged plants that rely on stable water bodies, particularly in hydrologically fluctuating habitats. This study revealed that morpho-physiological plasticity driven by water gradients may be a key mechanism contributing to the invasive potential of M. aquaticum, providing new insights into its possible expansion potential in zones with fluctuating water levels. Full article

Spent mushroom substrate (SMS) return is a vital strategy for agricultural waste recycling and soil fertility improvement, yet its ecological impacts of duration remain poorly understood. This study employed metagenomic sequencing to explore soil fertility, microbial dynamics, and nitrogen cycling across different SMS return durations (0, 1, and 3 years) within rice–mushroom crop rotation systems. Soil nutrients (organic matter, total nitrogen, total phosphorus) initially decreased and then increased throughout the rice growth cycle. The one-year return (y1) induced early nutrient depletion, whereas the three-year return (y3) significantly enhanced late-stage nutrient accumulation. With increasing duration, bacterial and archaeal assembly shifted from stochastic toward deterministic processes, while fungal diversity and stochasticity decreased continuously. Co-occurrence network analysis demonstrated that SMS return increased network complexity and intercommunity competition. This transition was accompanied by a functional shift in keystone taxa from those responsive to exogenous organic matter in y1 to those mediating nitrogen fixation, anammox, and sulfur metabolism in y3. Nitrogen cycling in y1 increased potential N₂O emission risks through nirS upregulation and nosZ downregulation, whereas y3 mitigated inorganic nitrogen loss by upregulating gene abundances of ammonia assimilation, nitrification, and DNRA genes. Notably, the structure of nitrogen-cycling genes fluctuated in y1 but was resilient to y0 levels in y3. These findings demonstrated that while initial SMS return triggered ecological fluctuations and environmental risks, continuous return (y3) achieved functional stability by reshaping microbial niches. This study highlights the importance of SMS return duration in balancing soil fertility enhancement with environmental risk mitigation in sustainable paddy ecosystems. Full article

Acetylcholinesterase (AChE) inhibition remains a key therapeutic strategy in the management of neurodegenerative disorders such as Alzheimer’s disease. In this study, the inhibitory potential of the gastric pentadecapeptide BPC-157 and two newly designed hybrid analogs, CIARA-1 and CIARA-2, was investigated for the first time. The hybrid peptides were rationally designed by combining a BPC-157-derived fragment with an arginine-containing C-terminal sequence to enhance interactions with the enzyme’s active and peripheral binding sites. Enzyme kinetics were evaluated using a modified Ellman assay, and inhibition parameters were determined through Lineweaver–Burk analysis. All tested compounds exhibited a competitive mechanism of inhibition, as evidenced by increased Michaelis–Menten constant (K_m) values with unchanged maximum velocity (V_max), indicating competition with the substrate at the catalytic site of AChE. Among the tested compounds, CIARA-1 demonstrated the highest inhibitory potency, reflected by the lowest inhibition constant (K_i = 0.24 mM) and IC₅₀ value (2.52 mM), followed by CIARA-2 (K_i = 0.29 mM; IC₅₀ = 2.73 mM) and BPC-157 (K_i = 0.48 mM; IC₅₀ = 2.80 mM). These findings were consistent with molecular modeling predictions, supporting stronger binding interactions for CIARA-1. Despite significantly lower potency compared to clinically used AChE inhibitors, the studied peptides represent a promising scaffold for further optimization. Overall, this work demonstrates that BPC-157 and its hybrid analogs act as reversible competitive AChE inhibitors, with enhanced activity observed for structurally modified derivatives. The results highlight the potential of peptide-based hybrid molecules as multifunctional candidates in the development of novel therapeutics targeting cholinergic dysfunction. Full article

In this study, cathodic arc deposition was employed to synthesize CrAlN/TiSiN nanostructured multilayer coatings on silicon wafer substrates. The effects of the multilayer architecture on the microstructure and corrosion resistance of the coatings were systematically investigated. The structural characteristics and performance of the deposited films were analyzed using scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), and electrochemical polarization measurements. The experimental results demonstrate that various CrAlN/TiSiN multilayer configurations were successfully deposited, forming dense multilayer coatings with a thickness of approximately 1–2 μm and a dominant FCC β₁-NaCl crystalline structure. The presence of nanostructured multilayer interfaces effectively inhibited columnar grain growth and contributed to microstructural refinement. XRD analysis revealed competitive growth between the (111) and (200) crystallographic orientations, indicating that the crystallization behavior is influenced by the interplay between surface energy minimization and strain energy accumulation. Contact angle measurements showed that all the coatings exhibited water contact angles exceeding 90°, indicating hydrophobic characteristics and potential anti-fouling capacity. In particular, the CrAlN outer layer structure presented lower surface free energy, which further enhances the coating system’s anti-fouling capacity. Electrochemical polarization results indicate that the corrosion current density of all the coatings remained in the order of 10⁻⁷ A/cm², demonstrating excellent chemical stability. Overall, the CrAlN/TiSiN nanostructured multilayer coatings exhibit pronounced interface strengthening and densification growth mechanisms, which effectively enhance the chemical stability of silicon-based material surfaces. These results could provide valuable insights for the structural design and optimization of high-performance protective coatings. Full article

Coral reefs in the Gulf of Eilat maintain a high diversity of ~100 stony coral species. Despite intense competition for a limited substrate, this raises fundamental questions about spatial organization and mechanisms of coexistence. This study combines deep learning species classification with spatial point-pattern analysis to quantify the frequency of intragenus versus intergenus competitive contacts among four dominant coral genera, Acropora, Favia, Platygyra, and Stylophora, across 12 standardized transects at four reef sites. The ResNet-50 convolutional neural network achieved 92.3% test accuracy for genus-level identification in field imagery of 1100 test images, enabling automated detection of 487 coral–coral competitive pairs exhibiting direct physical contact. Intragenus pairs comprised only 18.3% (89/487) of contacts, significantly below the 50% expected under spatial randomness (z = −14.0, p < 0.0001) with pair correlation functions g(r) > 1 at sub-meter scales indicating conspecific clustering. Genus-specific pair frequencies correlated strongly with relative abundance and spatial coverage (r = 1), with ecological traits explaining dominance patterns: fast-growing, competitive Acropora generated high contact rates, while stress-tolerant Favia and Platygyra prevailed through longevity and defensive competition. These findings demonstrate that intergeneric competition dominates despite local congeneric aggregation, maintaining diversity through niche partitioning rather than intransitive networks, even as coral cover declines amid rising temperatures above 0.05 °C yr⁻¹ and historical eutrophication. The deep learning workflow provides a scalable baseline for monitoring anthropogenic impacts on coral competition dynamics. Full article

Pulsed laser-induced phase change in silicon underpins applications from photonic device trimming to stealth dicing, yet predictive models that capture the non-equilibrium kinetics governing the competition between epitaxial recrystallization and amorphization remain limited. In this work, we developed a two-dimensional axisymmetric numerical model at the continuum level for picosecond laser-induced melting, resolidification, and amorphization of crystalline silicon at 532 nm laser wavelength, coupling transient heat conduction with Wilson–Frenkel interface kinetics and Lagrangian marker-based interface tracking. The model predicts a bounded amorphization window defined by lower and upper fluence thresholds, within which the central amorphous thickness exhibits a bell-shaped fluence dependence. Under a Gaussian beam, this window governs a morphological transition from a central amorphous spot to an amorphous ring. The predicted amorphization threshold of ≈0.22 J/cm² agrees with published experimental data for 20 ps, 532 nm irradiation. Parametric studies reveal that reducing the spot diameter or substrate temperature shifts or eliminates the upper threshold, transforming the bounded window into a monotonically increasing function, while increasing the pulse duration narrows the window symmetrically until collapse. These results provide quantitative guidelines for selecting irradiation parameters to control phase change in silicon photonic and laser processing applications. Full article

Background/Objectives: Low-carbohydrate (LCD) and ketogenic diets (KD) are increasingly adopted by athletes due to their ability to enhance fat oxidation and induce metabolic adaptations. While their effects on aerobic power and capacity have been widely investigated, their influence on anaerobic performance remains unclear. Given the strong dependence of high-intensity exercise on glycolytic metabolism and muscle glycogen availability, carbohydrate restriction may have significant implications for short-duration maximal efforts and repeated high-intensity exercise. Therefore, this systematic review and meta-analysis aimed to evaluate the effects of LCD and KD on anaerobic performance outcomes in trained athletes. Methods: A comprehensive search of five electronic databases (PubMed, SCOPUS, Web of Science, SPORTDiscus, and Cochrane Central Register of Controlled Trials) identified 13 unique studies (yielding 15 study-level entries across three anaerobic performance domains) meeting comprehensive inclusion criteria. Individual study sample sizes ranged from n = 5 to n = 65 participants, reflecting substantial inter-study variability that should be considered when interpreting pooled estimates. Outcomes included peak and mean power output, repeated sprint performance, blood lactate responses, and markers of substrate utilization. Study quality was assessed using the Newcastle–Ottawa Scale, and meta-analyses were performed using random-effects models where appropriate. Results: Overall, the effects of carbohydrate-restricted diets on anaerobic performance were domain-specific. Some studies reported maintained or slightly improved peak power during single maximal efforts, while others showed no effect. Impairments were more consistently observed in repeated high-intensity exercise. Repeated sprint performance was impaired in several studies, likely reflecting reduced muscle glycogen availability and limited glycolytic ATP production. Carbohydrate restriction consistently increased fat oxidation and was associated with lower blood lactate concentrations during high-intensity exercise. Random-effects meta-analyses yielded domain-specific pooled effect sizes: maintained-to-slightly-improved anaerobic power output (Cohen’s d = +0.29; 95% CI: −0.08 to +0.66), modestly impaired repeated sprint ability (d = −0.33; 95% CI: −0.80 to +0.14), and a large, consistent reduction in blood lactate concentration (d = −0.89; 95% CI: −1.20 to −0.58). Given substantial between-study heterogeneity in intervention durations (2 days to 12 weeks), dietary composition, athlete populations, and outcome measures (1RM, Wingate, CMJ within the power domain; varied protocols within the RSA and lactate domains), these pooled estimates should be interpreted as exploratory rather than confirmatory. Conclusions: LCD and KD appear to have domain-specific effects on anaerobic performance in trained athletes. Although single, short-duration efforts may be preserved in some contexts, repeated, high-intensity performance appears to be more susceptible to impairment. These findings highlight the importance of aligning dietary strategies with the metabolic demands of training and competition. Full article

Background/Objectives: Gold(I) complexes are promising bioactive agents with anticancer and anti-inflammatory potential. This study evaluated cytochrome P450 (CYP) interactions and in vitro pharmacokinetic properties of two Au(I)–triphenylphosphine complexes bearing 6-alkoxy-9-deazapurine ligands. Methods: Complexes [Au(HL_1,2)(PPh₃)] (HL₁ = 6-isopropyloxy-9-deazapurine, complex 1; HL₂ = 6-benzyloxy-9-deazapurine, complex 2) were investigated. Inhibition of nine human CYP isoforms was assessed in liver microsomes, and kinetics were analyzed using Dixon and Lineweaver–Burk plots. CYP binding was evaluated by UV–Vis difference spectroscopy. ADME properties (chemical/plasma stability, microsomal stability, plasma protein binding, and PAMPA permeability) were determined. Binding thermodynamics were analyzed by ITC. Results: Both complexes weakly inhibited most CYP isoforms, with stronger effects on CYP2C9 and CYP3A4/5. A non-competitive inhibition mechanism was observed, which may be related to the binding of the complexes to the substrate channels of CYP2C9 and CYP3A4, thereby limiting the active site’s accessibility to the substrate, as supported by molecular docking studies. UV–Vis spectra showed type I binding with Kd values of 9.32 µM (1) and 12.64 µM (2). Both compounds showed high chemical and plasma stability (>90%), moderate microsomal stability (~60% after 60 min), high plasma protein binding (~80%), and low passive permeability. Conclusions: Au(I)–triphenylphosphine complexes with 6-alkoxy-9-deazapurine ligands exhibit moderate CYP affinity and defined pharmacokinetic profiles, supporting further preclinical evaluation. Full article

Spotted wing drosophila (Drosophila suzukii; SWD) has become a globally invasive pest by ovipositing in ripening, intact fruit rather than decaying material, a niche distinct from most other drosophilids. An expanding body of work implicates microbes and microbially derived chemistry as key drivers of this ecology, shaping fly biology across life stages. However, much of this evidence is derived from microbiome surveys and observational comparisons, further constrained by uncontrolled diet history, laboratory rearing, and insufficient ecological context. We examine how the SWD microbiome differs in which taxa are present (composition), how flies pick up those taxa from fruit and maternal sources (acquisition), how long those taxa are retained across life stages (persistence), and how each of these varies with diet, geography, season, and host crops. We then address how microbial cues and fermentation state function as context-dependent drivers of adult attraction, avoidance, and oviposition, and how microbe-mediated interspecific interactions reshape substrate suitability and competition among drosophilids. Throughout, we critically evaluate experimental designs and identify gaps that impede causal inference. These include limited strain-level resolution, incomplete fungal characterization, and weak linkages between microbial community structure and host phenotypes. Key unresolved questions include how SWD maintains performance across diverse hosts, how microbes modulate sensory processing during seasonal shifts, and which microbial metabolites drive attraction, avoidance, and competition. Resolving these questions is a direct prerequisite for field-stable integrated pest management (IPM), including microbially informed behavioral lures, oviposition deterrents derived from pathogen- and competitor-associated volatiles, and competitor-mediated suppression strategies. The experimental priorities identified here translate directly into a roadmap for the next generation of mechanistically grounded, ecologically realistic SWD management tools. Full article

Sustainable southern highbush blueberry production in Florida is increasingly constrained by freshwater competition, variable rainfall, and the chemical vulnerability of coarse-textured and organic-based production media. Reclaimed water irrigation and biochar amendment are promising strategies for improving water use efficiency and root zone function, but their combined implications for blueberry systems remain insufficiently understood. This review synthesizes the current knowledge on blueberry production requirements, the regulatory and operational context of reclaimed water use, and the physical and chemical roles of biochar in sandy and pine bark-based substrates relevant to horticulture in Florida. Particular emphasis is placed on mechanistic links among reclaimed water chemistry, substrate properties, and root zone processes that govern salinity, pH drift, nutrient retention, and solute leaching. The literature indicates that reclaimed water can improve irrigation reliability and provide supplemental nutrients, but may also introduce sodium, chloride, boron, and other constituents, as well as alkalinity, which alter substrate chemistry and increase the risk of salinity stress and nutrient imbalance. Biochar may enhance water retention, cation exchange, and sorption capacity, but its effects are strongly dependent on feedstock, production conditions, aging, application rate, and substrate context. Overall, successfully integrating reclaimed water and biochar into blueberry systems requires substrate-specific and constituent-resolved evaluation under production conditions relevant in Florida. Full article

This paper presents a compact, single-layer substrate-integrated waveguide (SIW) bandpass filter for 5.8 GHz WiMAX applications. The filter achieves an improved performance trade-off through a novel hybrid design strategy that combines central vertical perturbation vias with symmetrically etched complementary split-ring resonators (CSRRs). This configuration implements a hybrid magnetic–electric perturbation within a single cavity, enabling simultaneous control of electric and magnetic field confinement. The proposed topology achieves an optimized balance among unloaded quality factor Q_u, insertion loss, selectivity, and structural simplicity. Through targeted intra-cavity field manipulation, the filter attains a Q_u of 239.7, a narrow fractional bandwidth of 3.08% (5.75–5.93 GHz), and a low insertion loss of 1.12 dB. It also delivers enhanced selectivity compared to conventional single-cavity designs and performs competitively with multi-resonator architectures. An equivalent circuit model accurately captures the via–CSRR interaction and agrees closely with full-wave electromagnetic simulations. Experimental results confirm excellent return loss and robust performance across the entire WiMAX band (5.725–5.850 GHz). Thus, the proposed filter offers a practical, high-performance, and manufacturable solution for selective RF front-end applications. Full article

Hypertension is a severe global public health issue. Food-derived angiotensin-converting enzyme (ACE)-inhibitory peptides have shown great potential as safe and effective alternatives to synthetic antihypertensive drugs. Camel milk is rich in bioactive peptides. This study aimed to screen for ACE-inhibitory peptides from hydrolyzed camel casein, explore their inhibitory mechanisms and endothelial protective effects in vitro, and reveal their potential antihypertensive pathways using network pharmacology. This study screened three peptides with angiotensin-converting enzyme (ACE) inhibitory activity from enzymatically hydrolyzed camel casein components: MVPFLQPK, VPFLQPKVM, and QKWKFL, with IC₅₀ values of 277.1, 396.9, and 486.9 μmol/L, respectively. Enzyme inhibition kinetics analysis indicated that MVPFLQPK exhibited a non-competitive inhibition pattern, VPFLQPKVM exhibited a mixed inhibition pattern, and QKWKFL exhibited a competitive inhibition pattern. Molecular docking revealed that all three peptides formed hydrogen bond interactions with ACE, and QKWKFL and VPFLQPKVM directly bound to the enzyme’s active site to inhibit substrate catalysis. Molecular dynamics simulation further confirmed the high stability of the three peptide–ACE complexes, with binding free energies from −34.24 to −51.19 kcal/mol. The primary contributing forces include hydrogen bonds, van der Waals interactions, electrostatic forces, and nonpolar solvation effects. Network pharmacology analysis suggested that these peptides may exert synergistic antihypertensive effects by regulating multiple blood pressure-related pathways, including the renin–angiotensin system, renin secretion, and calcium signaling pathways, by acting on key targets such as ACE, REN, SRC, and MMP9. Cell experiments demonstrated that all three peptides exhibited no cytotoxicity in the Ang II-induced HUVEC injury model, significantly promoted NO release, inhibited ET-1 secretion, and possessed endothelial protective potential. This study investigated the in vitro ACE-inhibitory mechanism of peptides derived from camel milk and their potential role in blood pressure regulation, providing experimental evidence for subsequent in vivo activity validation and the development of functional camel milk protein products. Full article