Search Results (9,855)

In this study, the biological activities of extracts obtained from Ramaria obtusissima were optimized using response surface methodology (RSM) and artificial neural networks-genetic algorithm (ANN-GA) approaches, and the chemical and biological profiles of the obtained extracts were evaluated with a holistic approach. Antioxidant potential was determined using FRAP, DPPH, TAS, TOS, and OSI parameters. It was found that the extract optimized with ANN-GA had significantly higher FRAP (242 ± 3 mg Trolox equivalent/g), TAS (6.64 ± 0.04 mmol/L), and DPPH (154 ± 3 mg Trolox equivalent/g) values compared to the RSM extract, while its OSI value was lower. Anticholinesterase activities were evaluated using IC₅₀ values, and it was determined that the ANN-GA extract exhibited a stronger inhibitory effect on acetylcholinesterase (95 ± 2 µg/mL) and butyrylcholinesterase (125 ± 3 µg/mL) compared to the RSM extract. Antiproliferative effects were investigated in A549, MCF-7, and DU-145 cell lines, and a significant and dose-dependent suppression of cell proliferation was observed in all three cell lines, particularly at concentrations of 100 and 200 µg/mL. The chemical profile was determined using LC-MS/MS and GC-MS techniques. Higher levels of phenolic compounds such as gallic acid (6694.5 ± 4.9 mg/kg), caffeic acid (3374.8 ± 4.9 mg/kg), and quercetin (1563.1 ± 2.3 mg/kg) were found in the ANN-GA extract. GC-MS analyses showed that the ANN-GA extract has a richer lipophilic component profile in terms of biologically active fatty acids and ester derivatives. The findings reveal that AI-assisted optimization offers a powerful and effective approach to enhancing the biological efficacy of mushroom-derived natural products. Full article

Background: In this study, we aimed to compare metabolomic profiles, biodistribution, and detoxification patterns of the novel SN-38 derivative NMe with irinotecan (IR), and to identify NMe-specific metabolites to evaluate its preclinical pharmacokinetic advantages. Methods: In vivo ADME studies were conducted for NMe, a 9-aminomethyl SN-38 derivative, and IR following a single intraperitoneal dose of 40 mg/kg in mice. Additionally, ADMET properties were predicted using ADMETlab and SwissADME tools for comparison. Levels of NMe and irinotecan absorbed into plasma, distributed to tissues, and metabolized were monitored in liver, lung, spleen, kidney, and stool samples at 15, 30, and 60 min post-administration. Tissue extracts were analysed using high-performance liquid chromatography (HPLC), liquid chromatography–electrospray ionization quadrupole time-of-flight-tandem mass spectrometry (LC-ESI-QTOF-MS), and nuclear magnetic resonance (NMR) techniques after lyophilization and reconstitution. We compared the metabolomic profiles of irinotecan and NMe. Results: We identified and confirmed NMe-specific metabolites, including 9-CH₂-S-cysteine conjugate, 9-CH₂OH, and NMe-formyl. Notably, novel irinotecan metabolites (IR-OH and IR-ΔE) were detected in small amounts in kidney samples. In some cases, two literature-known photodegradation products of irinotecan were present. NMe was found to quickly metabolize with different distribution to tissues, significantly greater to kidney and liver. Two SN-38 glucuronides, SN-38G(α) and SN-38G(β), were detected corresponding to α- and β-anomers. Where it was possible, NMe, IR and SN-38 were quantified using external calibration curves. In IR group, controlled and prolonged release of SN-38 was confirmed in all samples, yet SN-38G was observed in minority only in plasma, kidney, or lungs. In NMe groups, great relative amounts of SN-38 and SN-38G were detected. Greater content of SN-38G in NMe group than in irinotecan is expected to contribute to modulation and alleviation of some side effects in irinotecan-involved therapies, such as gastrointestinal toxicities (GIT). Conclusions: NMe shows a distinct metabolic profile characterized by rapid biotransformation, higher systemic glucuronidation of SN-38, and formation of unique metabolites, suggesting a potentially wider therapeutic window and reduced toxicity compared with IR. Full article

Paint manufacturing wastewater contains complex mixtures of solvents, resins, surfactants, pigments, and polymeric additives that result in high chemical oxygen demand (COD), toxicity, and poor biodegradability. Conventional physicochemical treatment provides limited removal of dissolved organics, and the pollutant-level behavior of paint effluents during biological treatment remains insufficiently characterized. This study addresses this gap by evaluating a sequential anaerobic–aerobic batch process treating three distinct synthetic paint wastewater samples. This study is a comparative investigation of sequential biological treatment across multiple paint wastewater variants, combined with high-resolution LC–MS to track compound-level transformations. Treatment performance was assessed through COD removal, biogas generation, pH and redox behavior, and LC–MS profiling of organic contaminants. The anaerobic stage achieved 70–95% COD removal depending on wastewater type. Aerobic polishing increased overall removal efficiencies, while PWW3 exhibited reduced stability during extended operation. LC–MS analysis showed substantial decreases in the number and intensity of chromatographic peaks and demonstrated degradation of phthalates, glycol ethers, organophosphate plasticizers, and solvent-derived compounds. The study provides integrated performance- and pollutant-level assessment of sequential anaerobic–aerobic treatment of paint wastewater and demonstrates the influences of wastewater heterogeneity in biological degradation pathways. Full article

Background: Artemisia annua L. is a medicinal plant with documented antimicrobial, antioxidant, and anti-inflammatory properties. Although widely studied for internal therapeutic applications, its topical use—especially in hydrogel-based systems—has not been thoroughly investigated. The aim of this study was to develop sodium alginate hydrogels containing Artemisia annua extract, supplemented with hyaluronic acid and dexpanthenol, and to evaluate their physicochemical characteristics as well as their biological activities in vitro and in vivo. Methods: Select bioactive constituents of the Artemisia annua extract were quantified using liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS). Hydrogels were prepared by cross-linking sodium alginate with a calcium carbonate–glucono-delta-lactone system and were formulated with or without hyaluronic acid and dexpanthenol. Physicochemical evaluations included measurements of moisture content, water-retention capacity, gelation time, and pH. The hydrogel microstructure was examined by scanning electron microscopy (SEM). Antioxidant activity was assessed using three methods: the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the ferric reducing antioxidant power (FRAP) assay, and the cupric reducing antioxidant capacity (CUPRAC) assay. Biocompatibility and regenerative effects were analyzed using cell viability assays and an in vitro scratch wound model on human keratinocyte cells. In vivo wound-healing efficacy was examined in rats with full-thickness skin excisions. Results: The extract contained high levels of methylated flavonoids and sesquiterpenes characteristic of Artemisia annua. Hydrogels supplemented with hyaluronic acid and dexpanthenol exhibited improved hydration stability and higher porosity. All formulations demonstrated measurable antioxidant activity, and those containing hyaluronic acid showed the strongest effects. The preparations were biocompatible and enhanced keratinocyte migration in vitro, with the combined hyaluronic acid–dexpanthenol formulation promoting the fastest wound closure. In vivo, Artemisia annua hydrogels accelerated wound healing by two to three days compared with untreated wounds. Conclusions: These results confirm the promise of Artemisia annua hydrogels for topical wound care and highlight the beneficial contributions of hyaluronic acid and dexpanthenol to their structural and therapeutic performance. Full article

To address the challenges associated with inter-module energy interaction and mode adjustment at load ports in distributed energy systems in the context of the energy transition, this paper proposes and designs a multi-port wireless energy interaction system based on LC series resonance and multi-coil magnetic coupling. The system aims to facilitate flexible energy interaction among power sources, energy storage units, and loads, as well as multi-modal port regulation. The system employs a multi-coil coupled full-bridge topology combined with a phase-shift control strategy to achieve energy exchange and power regulation among multiple ports. To meet the power demands of different ports, a port state control method incorporating a mode preset mechanism is proposed, enabling the intermediate port to switch seamlessly among input (source), output (load), and active relay modes. This paper analyzes the operating modes of a single port and establishes the dynamic mathematical model of the overall three-coil system as well as the small-signal model of the port output. Furthermore, it investigates the energy interaction mechanism to derive the operating characteristics and conditions under different modes, and elucidates the energy relay mechanism with zero active power consumption. A three-port hardware experimental platform was constructed based on a dsPIC33 controller. Experimental results indicate that: (1) the prototype achieved a maximum transmission power of 100 W; (2) the peak system efficiency reached $83.1\%$ under different load conditions; and (3) during mode switching, the system response time was less than 200 ms with no significant overshoot. The study demonstrates that the proposed topology and control strategy effectively realized dynamic energy interaction and seamless mode switching among multiple ports, providing a theoretical basis and engineering reference for multi-port energy interaction and wireless power transfer networks. Full article

Epilepsy remains one of the most prevalent neurological disorders, characterised by complex aetiology encompassing genetic, structural, metabolic, and inflammatory factors. Despite advances in neuroimaging and neurophysiological diagnostics, there is a persistent lack of sensitive and specific biomarkers to enable early diagnosis, risk stratification, and monitoring of therapeutic efficacy. Key epilepsy biomarkers include neurotransmitters, energy–related compounds, tryptophan pathway metabolites, and choline derivatives. Their determination employs liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS), high–performance liquid chromatography (HPLC) with electrochemical or fluorescence detection, gas chromatography with tandem mass spectrometry (GC–MS/MS), high–resolution mass spectrometry (HRMS), and proton nuclear magnetic resonance (¹H–NMR) spectroscopy, revealing metabolic disturbances in neurotransmission, energy metabolism, and oxidative stress associated with epileptogenesis. Among these techniques, LC–MS/MS currently provides the highest analytical sensitivity and specificity for quantifying low–abundance epilepsy–related metabolites, while HPLC with conventional detection remains a simpler and more cost–effective alternative for routine clinical laboratories. This review presents the current state of knowledge regarding chromatographic techniques applied to the analysis of mentioned metabolites, as well as therapeutic drug monitoring of antiepileptic drugs. Key sample preparation stages are also discussed. Various biological matrices–plasma, serum, urine, cerebrospinal fluid (CSF), dried blood spots (DBSs), and brain tissue—are evaluated. Novel approaches are also presented, including hair samples, microsampling techniques, and headspace analysis of volatile metabolites. Chromatographic techniques constitute the foundation of contemporary metabolomic research in epileptology, enabling biomarker identification and supporting personalised medicine. Further standardisation and translational validation remain necessary, as current evidence is insufficient for routine clinical implementation. Full article

CS is an environmental pollutant everywhere, but we still do not fully know how it hurts our skin. This study integrates LC-MS, network toxicology, molecular docking, and experimental validation in order to understand how CS causes skin involvement at the molecular level. By searching a database, constructing a PPI network and analyzing GO/KEGG, we found 57 candidate targets related to CS-induced skin damage. We found that STAT3, AKT1, TP53, CASP3 and IL-6 play the core roles, and PI3K-Akt, p53, JAK-STAT and apoptosis pathways may be crucial. Molecular docking analysis confirmed strong interactions between components of CS and these key targets. In vitro validation using HaCaT cells showed that CS exposure decreased expressions of STAT3 and AKT, but increased p53, CASP3 and IL-6. The inhibition of PI3K-AKT- and JAK-STAT-related responses, coupled with the initiation of p53-driven apoptosis, led to the observed cytotoxicity, functional impairment, oxidative stress and inflammation, which induced and aggravated skin damage. These findings provide a new perspective on the harmful effects of CS on the skin, providing both a theoretical basis for strengthening regulatory measures to limit exposure and opening new avenues for exploring relevant prevention strategies. Full article

The functional genomic mechanisms contributing to aging-associated decline in fertility in men remain insufficiently elucidated. This study investigated age-related alterations in the sperm metabolome of healthy fertile Arab men across three groups: young adult (21–30 years, n = 6), late adult (31–40 years, n = 7), and advanced age (41–51 years, n = 5). Metabolomics was performed using LC-MS/MS. Statistical/functional analyses were performed using MetaboAnalyst-Pro. A total of 380 metabolites were identified, of which 164 showed significant differences (p < 0.05) across age groups. Principal component analysis, partial least squares-discriminate (PLS-DA), and sparse PLS-DA consistently demonstrated distinct metabolomic clustering between young adult and advanced age groups. Notably, in the advanced-age spermatozoa, L-homocysteine was undetectable, while methyloctadecanoyl-CoA was uniquely abundant. Biomarker analysis identified 137 potential aging-sperm biomarkers (AUC = 1), including upregulated (e.g., pentadecanoyl-CoA, (3S)-3-hydroxylinoleoyl-CoA, CDP-DG(LTE4/20:4(8Z11Z14Z17Z)), uracil) and downregulated (e.g., (S)-hydroxyoctanoyl-CoA, DG(22:6/18:4), L-homocysteine, N-myristoyl serine) metabolites. These biomarkers participate in key sperm domains, including motility, energy metabolism, membrane remodeling, oxidative-stress regulation, and fertilization. In conclusion, advancing age disrupts sperm “metabolostasis” (metabolite homeostasis essential for normal function), compromising their physiological integrity and fertilization competence. The identified biomarkers offer promising targets for interventions to preserve sperm health and mitigate age-related fertility decline. Full article

N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) are lipid signalling molecules within the endocannabinoid system, which regulates numerous physiological processes and is implicated in diverse pathological conditions. Given the limited feasibility of obtaining human tissue samples, quantifying AEA and 2-AG in biological matrices is essential for understanding the endocannabinoid system in humans. While many studies have used blood samples for this purpose, the collection of this matrix typically requires invasive venipuncture, which limits the scalability and practicality of endocannabinoid research. This study validated extraction and LC–MS/MS methods for quantifying AEA and 2-AG (co-quantified with its isomer 1-AG) in minimally invasive matrices, including saliva and finger-prick blood microsamples, with acceptable linearity, recovery, reproducibility, and matrix effects. The assay additionally enabled exploratory quantification of arachidonic acid, oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and selected steroid hormones, supporting multiplexed assessment from a single sample. Analyte concentrations measured in blood microsamples did not directly correspond to plasma concentrations, indicating that microsampling is suited for assessing relative within-study changes rather than absolute plasma equivalence. Application of the method demonstrated that venipuncture did not significantly alter salivary AEA or 2-AG concentrations. Overall, this method provides a minimally invasive and accessible approach for investigating endocannabinoid dynamics alongside other physiological biomarkers. Full article

Flavor is a pivotal determinant of goat meat quality, influenced by multiple factors. This study investigated flavor formation from a lipid perspective by comparing two distinct breeds at two years old and fed the same diet: the high-altitude Xizang goat (XG; n = 6, 26.23 ± 0.72 kg), renowned for its unique meat flavor, and the low-altitude meat-type Jianzhou big-ear goat (JBG; n = 6, 63.93 ± 0.98 kg). Lipid profiles were analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS), and flavor variations were assessed using gas chromatography–mass spectrometry (GC–MS). We identified 630 significantly differential lipids (VIP > 1, p < 0.05) between the breeds. The XG group exhibited a distinct lipid composition characterized by a higher proportion of glycerophospholipids (45.1%) and the upregulation of specific species such as PC (13:0_16:0) and PE(16:0_20:5), whereas glycerolipids were markedly more abundant in JBG (24.3%) than in XG (6.4%). A total of 14 key volatile organic compounds (VOCs) were identified as potential drivers of flavor divergence based on the criteria of |log₂(fold change)| ≥ 1, VIP > 1, p < 0.05 and rOAV ≥ 1. Correlation networks revealed significant positive associations (r > 0.8, p < 0.05) between several upregulated glycerophospholipids—including PC (13:0_16:0), PE(16:0_20:5), PE(20:5_16:1), PMeOH(16:0_22:4), and PS(18:2_20:5)—and fruity esters such as ethyl heptanoate and butyl butyrate in XG meat, directly contributing to its more intense fruity sensory profile. Collectively, this study demonstrated that the phospholipid-rich lipidome of high-altitude XG served as a key substrate for generating fruity esters, which fundamentally distinguishes its more complex and preferred sensory profile from the triglyceride-dominated lipidome of JBG meat. These findings establish a potential molecular link between lipid composition and meat flavor, providing a biochemical explanation for traditional flavor preferences and highlighting the importance of lipid metabolism in determining the quality of goat meat. Full article

Corn is a critically important agricultural crop, with different parts consumed at specific growth stages—notably, fresh corn and corn grain. The field residue behaviors of clothianidin and phoxim in fresh corn and corn grain were investigated by using a QuEChERS technique combined with UPLC-MS/MS, and the dietary exposure risks of the insecticides were evaluated. Field trials were conducted under the recommended application conditions (2250 g active ingredient per hectare of 2% clothianidin and phoxim granules, applied once) at 12 agricultural regions across China under various climatic conditions to study the residue levels of pesticides. The samples were collected at harvest of fresh corn and corn grain, separately. The results indicated that the residues of the phoxim remained stable in all samples stored at −20 °C for 6 months (180 days). At harvest, the concentrations of clothianidin in fresh corn ranged from <0.01 to 0.027 mg/kg (below the MRL of 0.1 mg/kg established by Japan); the concentrations of phoxim in fresh corn were all below 0.01 mg/kg (below the Chinese MRL of 0.1 mg/kg). In corn grain, clothianidin residues ranged from <0.01 to 0.018 mg/kg (below the Chinese MRL of 0.02 mg/kg), while phoxim residues were below 0.01 mg/kg (below the Chinese MRL of 0.1 mg/kg). Dietary risk assessment based on Chinese pesticide registration status and the per capita dietary structure of Chinese residents showed that the national estimated daily intake (NEDI) of clothianidin for the general population was 0.49 mg, accounting for 7.8% of the adult acceptable daily intake (ADI), while NEDI of phoxim for the general population was 0.048 mg, accounting for 19.2% of adult ADI. The results suggest that the associated health risks are acceptable for the general population. On the basis of these findings, it is recommended to establish an MRL for clothianidin in fresh corn in China at 0.1 mg/kg. This study provided basic data on the use and safety of clothianidin and phoxim in fresh corn and corn grain to help the Chinese government formulate a maximum residue level for clothianidin in fresh corn. Full article

Peony seed meal (PSM), a protein-rich by-product of oil extraction from Paeonia ostii, represents an underutilized resource with significant potential for functional ingredient development. In this study, an integrated strategy combining artificial neural network (ANN)-guided hydrolysis, peptidomics, molecular simulation, and cellular validation was employed to identify antioxidant peptides from PSM. Neutrase was selected as the optimal protease, and hydrolysis conditions were optimized using a backpropagation ANN model (R = 0.9935), yielding a hydrolysate with strong radical-scavenging activity (DPPH^• IC₅₀ = 0.30 mg/mL; ABTS^•+ IC₅₀ = 0.07 mg/mL). LC–MS/MS identified 364 peptides, predominantly low-molecular-weight sequences. In silico screening highlighted four candidates (FRF, WQFR, FEFR, and RWL) with favorable binding toward ABTS^•+, DPPH^•, and Keap1. Molecular docking and 100 ns molecular dynamics simulations confirmed stable peptide–Keap1 interactions, particularly for FRF. Cellular assays demonstrated that FRF and RWL significantly protected HepG2 cells against H₂O₂-induced oxidative damage by restoring antioxidant enzyme activities (SOD, CAT, and GSH-Px). Collectively, this study establishes a systematic workflow for discovering plant-derived antioxidant peptides and supports the sustainable valorization of PSM as a functional food ingredient. Full article

Green Analytical Chemistry (GAC) provides a framework for reducing hazardous reagents, energy consumption, and waste. The topic has gained momentum across many chemical industries over the past 25 years; however, progress in implementing sustainable methods and conducting greenness assessments within forensic laboratories has been comparatively slow. The purpose of this review is to highlight green approaches to analytical separation methods, including greenness assessment metrics, that have been reported in the literature for forensic chemistry and toxicology applications and to raise awareness of GAC in the forensic field. Recent scientific literature highlights promising advances in greener sample preparation and chromatographic approaches, particularly in forensic toxicology and seized-drug analysis. Emerging trends include the use of green solvents, bio-based and deep eutectic solvent systems, and the rapid expansion of microextraction techniques such as SPME, LPME, MEPS, FPSE, and DLLME, which reduce solvent volumes, minimize waste, and support higher-throughput workflows. Parallel developments in portable and miniaturized chromatographic instrumentation such as miniaturized LC–MS systems with increased detection specificity and Lab-on-a-Chip applications show promise for in situ measurements in the field. Ambient ionization mass spectrometry—in particular, DESI and DART—has had a major impact on forensic chemistry by providing tools for the rapid and direct analysis of chemical compounds in complex matrices with little or no sample preparation. Greenness assessment tools—including AGREE, AGREEprep, Eco-Scale, GAPI, and BAGI—are increasingly applied to evaluate analytical methods in forensic chemistry and toxicology, including those used for novel psychoactive substances. Although many green methodologies are well documented, their routine implementation remains limited. The continued integration of green solvents, microextractions, portable instrumentation, and standardized greenness metrics will be essential for advancing sustainable forensic separations. Full article

Background: Hydroxytyrosol (HT) is a phenolic compound found in extra virgin olive oil that modulates oxidative and inflammatory status. However, clinical trials evaluating HT as a stand-alone supplement remain scarce, and its underlying mechanisms and pathway modulation are not yet fully understood. This study aimed to investigate the metabolic effects of HT supplementation in individuals with overweight and prediabetes using an untargeted metabolomics approach. Methods: An untargeted liquid chromatography–mass spectrometry (LC–MS)-based metabolomics analysis was performed on serum samples from 49 participants with overweight and prediabetes enrolled in a randomized controlled trial. Participants received either HT (15 mg/day for 16 weeks; n = 24) or placebo (n = 25). Global metabolomic profiling was used to compare metabolic changes between the two groups. Results: HT supplementation induced a distinct metabolic profile compared with placebo. Participants in the HT group showed reduced levels of nitrogenous base derivatives and arachidonic acid, together with increased concentrations of phosphatidylcholines, lysophosphatidylcholines and sphingomyelins. These alterations suggest modulation of two key metabolic pathways including purine degradation and arachidonic acid metabolism. Conclusions: These findings provide mechanistic insights into the biological effects of HT and support the integration of metabolomics and multi-omics approaches in future clinical studies to validate these pathways in larger populations. Full article

Background/Objectives: Developability assessment is a critical step in advancing antibody-based molecules toward clinical application. This evaluation typically begins during clinical candidate selection and continues throughout all modifications of the molecule during development. It is guided by the target product profile, which includes the intended administration route and regimen, formulation parameters, and process conditions encountered during manufacturing, storage, and delivery. While developability testing is well established for conventional therapeutic antibodies, strategies for assessing single-domain antibodies (sdAbs) and their conjugates remain underexplored. Here, we present a strategy to test the developability of sdAbs as a case study for two clinical candidates intended as precursors for the production of diagnostic tracers for clinical imaging. Methods: Assays were developed to evaluate chemical and thermodynamic stability, target binding affinity and capacity, and chelation efficiency (“chelatability”). Accelerated stability studies were conducted for both unconjugated sdAbs and their chelator conjugated forms following incubation at two pH conditions, at multiple time points, and after twelve freeze–thaw cycles to simulate process conditions and long-term storage. Analytical assays were applied stepwise in a hierarchical approach to minimize experimental effort and material consumption. Candidates exhibiting critical developability features were selectively addressed by assays with increasing precision. Results: A tailored panel of analytical assays optimized for low molecular weight proteins was established and applied to the two clinical candidates, identifying instability hotspots as well as potential mitigation strategies. Successful engineering of a candidate with an initially critical developability profile was achieved. Conclusions: This study demonstrates the implementation of a structured developability assessment strategy for sdAb conjugates. The approach integrates physicochemical and functional stability evaluations, supporting robust candidate selection, formulation development, and method optimization for this class of molecules. Full article