The rising incidence of antimicrobial resistance necessitates the development of sustainable and eco-friendly nanomaterials. In this study, silver-iron oxide nanoparticles (Ag-FeO NPs) were phyto-synthesized using Traganum nudatum seed extract as a natural reducing and stabilizing agent, and their physicochemical properties and antimicrobial activity were systematically evaluated. UV-Vis spectroscopy showed a characteristic absorption peak at 359 nm, providing supportive evidence of nanoparticle formation. Fourier-transform infrared spectroscopy revealed functional groups at 1,645 and 3,315 cm[-1], indicating the involvement of plant-derived phytochemicals in nanoparticle stabilization. Transmission electron microscopy analysis showed heterogeneous spherical and rod-like nanostructures with moderate aggregation, while scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy qualitatively indicated the presence of silver and iron, together with oxygen and carbon. Dynamic light scattering analysis showed an average hydrodynamic particle size of 7.3 nm and a broad particle size distribution (PDI = 0.60), with a zeta potential of -1.36 mV. GC-MS profiling identified bioactive metabolites, including 3-(octanoyloxy)propane-1,2-diyl bis(decanoate), n-hexadecanoic acid, hentriacontane, and lidocaine, potentially contributing to nanoparticle synthesis and bioactivity. Ag-FeO NPs exhibited significant antimicrobial activity against Escherichia coli, methicillin-resistant Staphylococcus aureus, and Candida albicans. SEM analysis of C. albicans revealed severe ultrastructural damage, including surface deformation and cell wall disruption. Ag-FeO NPs produced greater reductions in MCF-7 cell viability than in MCF-10A non-tumorigenic epithelial cells, although a clear concentration-dependent response was not observed within the tested range. Computational prediction analyses using PASS, SwissTargetPrediction, SwissADME, and ProTox-II indicated that several identified phytochemicals possess antimicrobial and antineoplastic potential together with favorable pharmacokinetic characteristics. Overall, the integration of green synthesis, experimental validation, and computational modeling highlights the potential of T. nudatum-mediated Ag-FeO NPs as effective and sustainable agents for biomedical applications.

A simple, rapid, and environmentally friendly dispersive liquid-liquid microextraction (DLLME) method using hydrophobic natural deep eutectic solvents (NADES) was developed for the simultaneous determination of six parabens and phenoxyethanol in water samples. The extraction performance of several NADES composed of thymol, menthol, and fatty acids was evaluated, selecting a thymol: decanoic acid system (2:1 M ratio) as the optimal extractant. Critical experimental variables were optimized using a multivariate approach combining Plackett-Burman and central composite designs. Under optimal conditions, the method provided high enrichment factors (85 - 133), good precision (RSD < 13%), and limits of detection between 0.065 and 0.56 ng mL[-1]. The method was applied to analyze different water samples, including tap, river, and wastewater samples obtaining recoveries between 78% and 118% for all the analytes in the spiked samples. The greenness and practicability of the developed method were evaluated using ChlorTox, AGREE, AGREEprep, and BAGI metrics, confirming the reduced environmental impact of the proposed approach, mainly due to the use of bio-based solvents and miniaturized extraction procedure. This method represents a sustainable and efficient alternative for monitoring emerging preservatives in environmental waters.

ObjectiveDescribe concurrent use of two long-acting injectable (LAI) antipsychotics in selected patients with treatment-resistant schizophrenia and persistent aggression at a forensic health facility. Evidence remains limited for this off-licence strategy.MethodsRetrospective case series conducted at a specialist forensic psychiatric hospital in Melbourne, Australia. All inpatients using concurrent LAI antipsychotics between March 2022 and March 2023 were included (N = 26). De-identified clinical data, including information for behavioral outcomes (Dynamic Appraisal of Situational Aggression [DASA]), institutional incidents, adverse effects and Defined Daily Dose (DDD) were extracted. Analyses were descriptive with exploratory unadjusted odds ratios.ResultsConcurrent LAI antipsychotics were predominantly prescribed to males (24/26, 92.3%) with chronic schizophrenia. Persistent aggression (22/26, 84.6%) was the commonest indication. Most frequent combination was olanzapine pamoate and zuclopenthixol decanoate and DDD median was 2.17 (range 0.48-10.13). Although the study design precluded identifying causal relationships, improvements were observed in DASA scores (21/26, 80.8%), incident frequency (22/26, 84.6%), and as-required-medication use (19/26, 73.1%). Adverse effects were common.ConclusionsSelected forensic patients with high-risk behaviors may benefit from concurrent LAI antipsychotics. Enhanced side-effect monitoring and multidisciplinary oversight are required when used. Data interpretation was limited by observational design, concomitant medications, and absence of standardized symptom measures.

Sour jujube (Ziziphus jujuba Mill. var. spinosa) is an ecologically and economically important fruit widely utilized in the functional food industry. However, the geographical variation in its volatile flavor profile and the potential odor relevance of individual volatile features remain insufficiently understood. In this study, volatile profiles of commercial sour jujube pulp samples labeled as originating from eight representative geographical regions across China were characterized using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). A total of 1296 putative volatile annotations were obtained, including esters, aldehydes, alcohols, acids, ketones, terpenoids, hydrocarbons, and other compounds. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed distinct distribution patterns among several sample groups. The OPLS-DA model showed acceptable internal validation performance, with cumulative R[2]X, R[2]Y, and Q[2] values of 0.967, 0.891, and 0.811, respectively. Medium-chain fatty acid ethyl esters, including ethyl dodecanoate, ethyl decanoate, and ethyl octanoate, contributed strongly to the multivariate differentiation of SDDY samples. Odor activity value (OAV) analysis further indicated that volatile abundance was not necessarily proportional to predicted odor contribution. Several trace volatile features with low reported odor thresholds, such as 1-nonen-3-one, 2-methoxy-3-(2-methylpropyl)pyrazine, and benzenemethanethiol, showed high calculated OAVs and may be important aroma-relevant candidates. Overall, this study provides an integrated volatile-profiling and OAV-based approach for characterizing compositional differences among commercial sour jujube pulp samples from different reported origins. Because the samples were commercially sourced and no independent external validation or direct sensory evaluation was performed, the results should be interpreted as exploratory evidence of origin-associated differentiation rather than as a validated geographical authentication system.

Background/Objectives: This study examined whether dexamethasone (Dex) and decanoic acid (DA) exert complementary effects on inflammatory signaling, catabolic gene expression, and peroxisome proliferator-activated receptor gamma (PPARγ) activation in human chondrocytes. Methods: Two donor-specific primary human chondrocyte models, each derived from a single knee donor, were used, in which cells were treated with Dex (≤0.1 µM), DA (≤500 µM), or combinations thereof. Acute Interleukin-1β(IL-1β)-induced PGE2 release was evaluated in normal donor cells, whereas prolonged transcriptional responses and PPARγ DNA-binding activity were evaluated in OA donor cells. IL-1β-induced prostaglandin E2 (PGE2) release was measured by competitive ELISA after 24 h. Glyceraldehyde-3-phosphate dehydrogenase-normalized transcription of Collagen type II alpha 1, Collagen type I alpha 1, Aggrecan, SRY-Box Transcription Factor 9, Runt-Related Transcription Factor 2, and Matrix Metalloproteinase 13 (MMP13) was assessed by qRT-PCR at 7, 10-14, and 20-28 days. In addition, PPARγ DNA-binding activity was measured after 1 week. Interactions were evaluated by Loewe additivity and highest single agent (HSA) analyses. Results: Dex and DA each reduced PGE2 release, whereas co-treatment increased potency and maximal inhibition, with a Loewe combination index of 0.4 at 1 nM Dex plus 19 µM DA. In the temporal analysis, Dex plus DA showed a positive MMP13 ΔCt difference versus Dex at 10-14 days (2.42 ± 2.14; p = 0.065) and a more consistent difference at 20-28 days (1.11 ± 0.25; p = 0.016). This agreed with fixed-dose HSA findings at 14 and 28 days (ΔHSA ≈ -75 for 0.1 µM Dex plus 100 µM DA versus Dex). Co-treatment was also associated with increased PPARγ activation beyond the HSA reference (ΔHSA ≈ 0.09 for 0.1 µM Dex plus 100-250 µM DA versus Dex). Conclusions: Dex plus DA co-treatment produced complementary effects on acute PGE2 inhibition, as well as late-onset MMP13 suppression and PPARγ activity in the donor-specific chondrocyte models studied. These hypothesis-generating findings provide an in vitro rationale for future evaluation of this combination as a corticosteroid-sparing strategy.

This study presents a novel, selective, and rapid magnetic solid-phase extraction (MSPE) method coupled with HPLC-DAD for the trace-level determination of apremilast (APM). To achieve high extraction efficiency and minimize matrix interferences, Fe3O4 magnetic nanoparticles were functionalized using a synchronized trimethoxymethylsilane (TMMS) and decanoic acid modification strategy for the first time. The synthesized Fe3O4@TMMS/decanoic acid sorbent was comprehensively characterized via XRD, FT-IR, SEM, and EDX to confirm successful surface functionalization and morphological stability. Key extraction parameters, including sample pH, desorption solvent type and volume, and adsorption/desorption times, were systematically optimized. Under optimal conditions (pH 5.0, isopropyl alcohol as desorption solvent), the method exhibited a robust linear range of 125.0-1000.0 ng mL[-1] for APM. The practical reliability of the developed protocol was validated with triplicate analyses of 100 ng per mL APM solutions, yielding relative standard deviations (RSD) below 5.1% and excellent recovery values between 95.3% and 103.2%. The results demonstrate that this functionalized magnetic sorbent offers a high-capacity, cost-effective, and highly reproducible alternative for the routine monitoring of apremilast in complex matrices. The overall method performance and eco-friendliness were quantitatively validated using AMRI (70), AGREE (0.70), AGREEprep (0.63), and SAMI (26) metrics, establishing the procedure as a reliable and sustainable analytical tool.

Kirkwood-Buff (KB) theory connects measurable thermodynamic properties with radial distribution functions and particle-number fluctuations accessible from molecular dynamics (MD) simulations. Although KB theory has been used to determine molar volumes, isothermal compressibilities, and solute or solvent activities from MD data, activity calculations have largely been focused on binary mixtures. In this work, we extend the application of KB theory to the calculation of water activity in multicomponent aqueous solutions with an arbitrary number of independent thermodynamic components. We adapt a generalized formulation to evaluate the required chemical-potential derivatives numerically, avoiding the explicit derivation of increasingly complex analytical expressions. The resulting automated workflow requires only MD trajectories and molecular topologies as input. We evaluate the approach using water-ethanol mixtures, aqueous NaCl solutions, mixed NaCl-LiCl solutions, and sodium decanoate solutions at low and high concentrations, a surfactant of relevance to atmospheric aerosol formation and climate modelling. The calculations reproduce the main experimental trends and illustrate the effects of force-field selection, KBI convergence, and solution microheterogeneity. Rigorous treatment of electrolyte solutions at exact electroneutrality requires an additional neutral-component formulation. Overall, the framework provides an automated route for estimating water activity in complex multicomponent solutions and identifies the principal limitations requiring further methodological development.

Curcumin has considerable therapeutic potential; however, its poor solubility and permeability limit its clinical applications. We evaluated menthol-based hydrophobic deep eutectic solvents (HDES) as oil phases in microemulsions to address these challenges. HDES were formulated by combining l-menthol with acids (lactic, decanoic, dodecanoic, and oleic acids) and incorporating them into microemulsions using surfactant mixtures of Cremophor RH40 (CrRH40) and diethylene glycol monoethyl ether or CrRH40 and Labrasol, with a 3 : 7 oil-to-surfactant ratio. Oleic acid, coconut oil, and medium chain triglyceride were used as the conventional oil phase. Physical properties, curcumin solubility in microemulsion, and their effects on in vitro permeability using synthetic membranes were assessed. Although oleic acid-based microemulsions (CLO) demonstrated higher curcumin solubility (54.5 mg mL[-1]) than HDES-based microemulsions (14.6-24.0 mg mL[-1]), curcumin permeation in oleic acid-based microemulsions was modest. In contrast, optimized HDES systems, particularly CL2MDO (menthol : dodecanoic acid, 2 : 1, as oil phase), achieved 116 µg cm[-2] cumulative curcumin permeation over 12 h, significantly surpassing conventional formulations (CLO, achieving 20.0 µg cm[-2] curcumin permeation) (p < 0.05). In oleic acid-menthol (HDES)-based formulations, increasing the menthol-to-oleic acid proportion enhanced permeation. CL2MO (menthol : oleic acid, 2 : 1) achieved 64.5 µg cm[-2] cumulative curcumin permeation at 12 h, compared to 40.0 µg cm[-2] in CLMO (menthol : oleic acid, 1 : 1) and lower at 37.2 µg cm[-2] in CLM2O (menthol : oleic acid, 1 : 2). Enhanced permeability was correlated with a 2 : 1 menthol-to-acid ratio using CrRH40 and Labrasol as surfactant mixtures. The menthol-to-acid ratio critically influenced permeation efficiency. The combination of HDES with microemulsion technology provides a strategy for the transdermal delivery of hydrophobic compounds, outperforming conventional oils in permeation.

Wutou decoction (WTD) is a traditional remedy in Chinese medicine for rheumatoid arthritis (RA). However, its active ingredients are complex, and how it counteracts RA is still not clear. The objective of this research was to investigate the key components and targets of WTD action. RA-related genes were analyzed using the GSE55235 dataset. The active components of WTD were analyzed using online databases. Component-target-pathology (CTP) networks were built using the Cytoscape software. The functions and pathways of the key targets were analyzed using GO and KEGG. The component-target interaction was assessed by molecular docking. Moreover, the impact of WTD on RA progression and its mechanism were validated using cell and animal experiments. The results showed that 1361 genes were related to RA, and they were enriched in 2035 biological processes and 97 signaling pathways. The five herbs of WTD had 221 common targets, and each herb had numerous components. A total of 66297 interactions were found among 440 active ingredients and 2638 targets within the WTD in the CTP network. Next, 114 core functional component groups were selected, and the types and quantities of target-enriched signaling pathways they covered were greater than those of RA-related genes alone. In vivo, WTD attenuated RA-induced arthritis and bone destruction. In vitro, benzoic acid, quercetin, apigenin, and decanoic acid inhibited the inflammatory response of macrophages by inactivating the PI3K/ATK and MAPK pathways. In conclusion, WTD exerts a therapeutic effect on RA through multi-component and multi-target, providing novel methods to study the mechanism of WTD.

Post-acidification during storage limits the use of multiple probiotics in fermented dairy products. In this study, the ldh gene was deleted in Lacticaseibacillus paracasei Zhang (LCZ), resulting in 45% reduction in lactic acid production. Co-fermentation of the engineered strain with commercial starters effectively controlled post-acidification, maintained a stable pH (4.5-4.3) over 28 d, and increased production of volatile compounds (acetoin, decanoic acid, and dodecanoic acid) and bioactive metabolites (acetic and succinic acids). Metabolic analysis revealed that ldh deletion activated acetoin biosynthesis (750 ng/mL) and redirected carbon flux toward malic, and acetic acids. The modification also promoted amino acid catabolism (L-alanine, L-cysteine, and L-asparagine) to pyruvic acid, enabling nitrogen-carbon co-utilization. This study presents a promising solution for developing stable probiotic dairy products and provides new insights into probiotic metabolic engineering.

It is unknown whether the transport protein serum albumin extracts fatty acid (FA) monomers from aggregates and causes deaggregation. We studied the effect of human and bovine serum albumin on spin-labeled FAs 5/16-DOXYL stearic acid in phospholipid vesicles, in mixtures with decanoic acid (DA), and as pure aggregates. With continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy, we distinguished and quantified free, aggregated, and albumin-bound FAs by their rotational dynamics, local concentrations, and polarities under different conditions. Our study unveils complex triangular equilibria between albumin and monomeric and aggregated FAs. The EPR spectra and altered aggregate sizes observed via dynamic light scattering confirm albumin-aggregate interactions. These argue for a dock-and-load FA transfer mechanism of albumin, while the binding of free FAs induces deaggregation. Similar effects on protein- or polymer-based aggregates could affect their use as drug carriers and guide future strategies in drug delivery or in the treatment of aggregation-related diseases.