Search Results (2,958)

The increasing interest in valorizing agricultural by-products has positioned grape pomace as a rich source of bioactive compounds. This study developed an effect-directed extraction (EDE) approach guided by bioactivity quantification on thin layer chromatography (TLC). Twelve grape pomaces were screened based on antioxidant and tyrosinase inhibitory properties. Using hydroalcoholic solvent (ethanol:water, 1:1), the two most promising sources (Malbec from San Rafael) were subjected to response surface methodology (RSM) to optimize extraction of anti-browning and antioxidant compounds visualized as TLC spots. Temperature and time were optimized (76 °C, 45 min), and samples were analyzed using TLC coupled with DPPH and laccase inhibition bioautography. Antioxidant compounds showed retention factor values on TLC plates of 0.37 and 0.75 (DPPH/ABTS-active), while laccase inhibition occurred at Rf 0.35, coinciding with the primary tyrosinase inhibition zone. However, subsequent bioassay-guided HPLC fractionation and HRMS/MS analysis revealed that tyrosinase and laccase inhibitions are mediated by distinct compounds within this bioactive zone, highlighting a synergistic multi-target effect in the optimized extract that is retained throughout the process. The primary tyrosinase inhibitor at Rf ~0.35 was tentatively elucidated as an acylated anthocyanin, consistent with malvidin-3-O-(p-coumaroyl)glucoside. Optimized extracts were evaluated on Pink Lady apple slices at different timepoints. The browning index was reduced by 25% versus the control at 15 h, confirmed by significantly lower ΔE values (p < 0.05). The process requires only food-grade solvents and conventional equipment, facilitating scale-up for grape pomace generated worldwide. Validating the EDE strategy, this TLC-guided approach successfully tracked and preserved the primary anti-tyrosinase activity from the crude waste matrix down to the tentatively identified molecule, contributing to circular economy objectives in the wine industry. Full article

Phosphonyl tyrosine is one of the main biomarkers to confirm exposure to highly lethal organophosphorus nerve agents (OPNAs) in vivo. However, a critical challenge remains unresolved: ionization suppression occurs during the analysis of phosphonyl tyrosine by high-resolution mass spectrometry (HRMS) or tandem mass spectrometry (MS/MS), which is induced by the high concentrations of free amino acids present in the digestion solution. In this study, based on the broad-spectrum immunomagnetic beads with high affinity antibodies, a non-targeted early warning and verification strategy was developed. Compared with the recommended operating procedures for analysis in the verification of chemical disarmament, the total analysis time was reduced from several hours to about 30 min. Moreover, the detection sensitivity was increased by nearly one order of magnitude, and the detection limit (LOD) was 0.01 ng/mL. Furthermore, the screening strategy can cover all OPNAs listed as 1A.01, 1A.02 and 1A.03 in Schedule 1 of the CWC. Therefore, we have developed a rapid, sensitive, and broad-spectrum approach to accurately screen for OPNAs exposure, while also offering a novel strategy and technical support for chemical defense and occupational health assessment. Full article

Retaining the green workforce, employees driving sustainability and environmental innovation, is essential for organizational resilience and long-term environmental goals. While prior Green HRM research has primarily relied on survey-based methodologies and theoretical frameworks to examine retention factors, these approaches lack predictive capability and fail to provide actionable, employee-specific insights. This study advances beyond descriptive and correlational analyses by employing explainable artificial intelligence (XAI) to develop a transparent, data-driven framework for identifying attrition drivers and quantitatively evaluating retention strategies. Unlike existing studies that rely on self-reported perceptions, our approach leverages objective HR data and machine learning to predict individual-level attrition risk with calibrated probabilities. Leveraging the IBM HR Analytics dataset as a proxy for sustainability-focused roles, we construct an interpretable logistic regression model with strong predictive performance and isotonic regression calibration. Global and local interpretability techniques, including SHAP, LIME, and permutation importance, show that non-monetary factors, such as excessive overtime, frequent business travel, and limited promotion opportunities, have a greater impact on turnover risk than salary levels. These findings align with Green Human Management (Green HRM) principles, which emphasize work–life balance and employee well-being. Crucially, our policy simulation framework, absent from prior Green HRM studies, demonstrates that eliminating overtime could reduce predicted attrition probability by 17.35% for affected employees, potentially retaining 31 staff members, substantially outperforming modest salary adjustments. This work expands the value of predictive AI into HR analytics by consolidating HR analytics with Green HRM through a novel methodology that bridges the gap between prediction and actionable intervention. It represents the first systematic integration of XAI-based predictive modeling with counterfactual policy simulation in environmentally conscious sustainable organizations. Full article

Studies of natural products and their semisynthetic derivatives are a valuable source of therapeutic agents. The aim of this work was to obtain new 30-phosphoramidate derivatives of betulin and determine their biological potential. The synthetic approach utilized the Staudinger reaction (the introduction of a phosphoramidate group), the Steglich reaction (the introduction of an alkynyl group), and the Jones reaction (the introduction of a carboxyl group). The structures of the target compounds were determined using spectroscopic methods (¹H NMR, ¹³C NMR, ³¹P NMR, and HRMS). The new derivatives were tested for antiproliferative activity against MV4-11, A549, MCF-7, PC-3, and HCT116 cancer cells and against normal MCF-10A cells using the MTT and SRB methods. Apoptosis studies were performed for the most active compounds (6B and 7A), potential molecular targets (AutoDock software) were identified, and lipophilicity parameters (RP-TLC method, SwissADME website) were determined. The greatest effect on apoptosis and caspase 3/7 activation was observed for the diester derivative 7A. Compound 7A showed a high lipophilicity parameter in the study group. Full article

Chronic kidney disease (CKD) affects more than 10% of the population and is associated with a persistent, low-grade inflammatory state that accelerates tubulointerstitial fibrosis, worsens prognosis, and increases cardiovascular risk. This review aims to synthesize current knowledge on specialized pro-resolving mediators (SPMs) in the context of CKD pathophysiology, biomarkers, and therapeutic potential. We discuss key anti-inflammatory and pro-resolving mechanisms of SPMs that translate into nephroprotective and antifibrotic effects in experimental kidney models. The review summarizes data on EPA/DHA supplementation, including its impact on lipid profiles, inflammatory biomarkers (CRP, IL-6, TNF-α), and oxidative stress in patients with CKD. We also highlight contemporary analytical methods for biomarker assessment (LC-MS/MS, UHPLC-HRMS) and their potential for monitoring inflammatory activity across its phases (initiation, attenuation, resolution), CKD progression, and responses to ω-3/SPM-based interventions. Finally, we discuss the therapeutic potential of SPMs, as well as safety considerations and pharmacological interactions. In conclusion, SPMs and ω-3-derived mediators represent promising research and clinical targets as markers and modulators of inflammation in CKD, but require further validation in well-designed prospective studies. Full article

Sustainable food production systems based on the use of biofertilizers and soil improvers are proposed to mitigate agricultural-related environmental impacts and address the climate crisis. In particular, plant growth-promoting microbes (PGPM) and biochar (Char) have been reported to improve plant growth, soil quality, and crop yield; however, their effects on food quality remain debated. In this study, untargeted metabolomics based on ultra-high performance liquid chromatography–ion mobility–high-resolution mass spectrometry (UHPLC-IMS-HRMS) and proton nuclear magnetic resonance spectroscopy (¹H-NMR) are proposed to achieve a comprehensive investigation of the effects of Char, PGPM and Char+PGPM on durum wheat. A total of 88 metabolites were annotated by UHPLC-IMS-HRMS, mainly belonging to carbohydrates, flavones, flavonoids, glycerophospholipids, and glycolipids, while 30 compounds were annotated by ¹H-NMR, mostly amino acids and short-chain carboxylic acids. The two datasets were merged with the gluten protein content dataset by using low- and mid-level data fusion approaches, obtaining models that exhibit excellent classification performance. Integrated analysis highlighted that the combined Char+PGPM treatment induced metabolic changes across multiple chemical classes, including enrichment of flavonoids and lipids, and downregulation of carbohydrate metabolites, suggesting a redistribution of carbon resources and modulation of secondary metabolism with potential implications on wheat grain quality. Full article

1,4-Dimethoxy-2,3-dinitrobenzene (1) reduction using sodium hydrosulfite resulted in 3,6-dimethoxybenzene-1,2-diamine (2) and 3,6-dimethoxy-2-nitroaniline (3) in 24% and 59% yields, respectively. Nitroaniline 3 was acetylated with acetyl chloride to give N-(3,6-dimethoxy-2-nitrophenyl)acetamide (4) in a 65% yield and with acetic anhydride to give N-acetyl-N-(3,6-dimethoxy-2-nitrophenyl)acetamide (5) in 78% yield. Novel compounds 4 and 5 were characterized by FT-IR, ¹H and ¹³C-NMR, and HRMS. The X-ray crystal structure of acetamide 4 is also presented. Full article

Antimicrobial resistance (AMR) remains a major threat to modern medicine, fueled by the excessive use of antibiotics and the spread of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). In this study, we designed and synthesized a series of 2-aryl-4-aminoquinazoline derivatives bearing an aminoalkylimidazole linker, combining two pharmacophoric motifs associated with antimicrobial activity. Starting from anthranilamide, the compounds were prepared in three straightforward steps, affording good yields and high purity. Their structures were confirmed by FT-IR spectroscopy, ¹H and ¹³C nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). Biological evaluation showed that series 5 exhibited strong selectivity toward S. aureus, with compounds 5c and 5d displaying minimum inhibitory concentrations (MICs) between 2.2 and 4.4 µM. No significant activity was observed against other tested strains. Cytotoxicity assays in HepG2 cells revealed moderate to low inhibition. Molecular docking indicated preferential binding to dihydrofolate reductase (DHFR) and relevant interactions with topoisomerase IV, resembling reference inhibitors. ADME analysis predicted favourable absorption, blood–brain barrier permeability, and compliance with Lipinski’s rules. Full article

Per- and polyfluoroalkyl substances (PFAS) are synthetics prized for their chemical stability and functionality. Legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have been phased out due to their persistence and toxicity. This study assessed exposure to both legacy and emerging PFAS in 281 urine samples from 8-year-old children participating in the (Infancia y Medio Ambiente) INMA Asturias birth cohort (northwest Spain), a region with a strong industrial background. Dietary and household information was collected via questionnaires, and urine samples were analysed using ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS) with full-scan acquisition in independent all-ion fragmentation mode. A suspected screening approach was applied to discover previously unreported PFAS and expand the detectable chemical profile, complemented by targeted analysis of 29 compounds selected for their persistence and regulatory relevance. Among them, 17 compounds were confirmed and quantified. The combined targeted and suspect-screening approach also identified novel PFAS, including fluorotelomer carboxylic acids, demonstrating the value of LC-HRMS for detecting unregulated compounds. Emerging PFAS showed the highest detection frequencies and concentrations: trifluoroacetic acid (TFA) and hexafluoropropylene oxide dimer acid (HFPO-DA, GenX) were detected in 63% and 27% of samples, respectively, with GenX reaching 10.1 ng/mL, whereas PFOA and PFOS were detected less frequently (8.5% and 3.2%) and at concentrations below 1 ng/mL, highlighting the need for epidemiological studies to achieve comprehensive PFAS exposure assessments. Associations with dietary habit exposure estimates point to dairy, protein-rich foods, vegetables, and drinking water as the main contributors. Full article

With the advancement of digital technology and Industry 4.0, artificial intelligence (AI) is gradually embedded in human resource management and has become an important digital foundation to support the sustainable transformation of enterprises. However, the research in the manufacturing context, particularly through the challenge perspective at different levels, remains fragmented. This work represents a systematic review of 347 articles from Scopus and Web of Science from 2000 to 2025 and employs a dual-method analysis strategy embracing metrics and in-depth coding on 100 core publications. Excel, Bibliometrix, CiteSpace, Latent Dirichlet Allocation (LDA), and VOSviewer were utilized for quantitative analysis, while open–axial–selective coding of the Grounded theory approach was applied to generate qualitative results. The findings revealed six key challenges in integrating AI-HRM within manufacturing and six approaches to solve the identified issues. The Challenge–Approach Matching Matrix was constructed, illustrating the suitability of different pathways for addressing specific challenges. Analysis of thematic evolution in AI-HRM research resulted in the identification of three distinctive phases and demonstrated a consistent shift from technology-centric approaches towards human–machine collaboration. The primary contribution of this research lies in proposing a Multi-Level Embedded Framework providing a complex view of AI-HRM in a manufacturing sector at micro, meso, and macro levels. The absence of sustainable HR transformation through AI integration was identified as the critical challenge at the macro level. This research provides theoretical and practical implications for designing the sustainable HRM system based on ESG principles and favors the United Nations Sustainable Development Goals 9 and 12. Full article

Over 70 mutations in the transforming growth factor beta-induced (TGFBI) gene are associated with corneal dystrophies that impair vision. The R555W hotspot mutation is a major cause of granular corneal dystrophy type 1 (GCD1). Here, we evaluated the technical feasibility of CRISPR/Cas9-mediated editing of the R555W mutation in peripheral blood mononuclear cells (PBMCs) obtained from a patient with GCD1. Three single guide RNAs (sgRNA1–3) and matched single-stranded oligodeoxynucleotide donors (ssODN1–3) were designed and co-transfected into PBMCs. Transfected cells were enriched by flow cytometric sorting, with GFP-positive cells representing approximately 2–4% of the total electroporated population. Editing outcomes were initially screened using high-resolution melting (HRM) analysis, and the sgRNA3–ssODN3 combination identified as the most promising candidate was subsequently validated by next-generation sequencing (NGS). Sequencing revealed a homology-directed repair efficiency of 98.2% among GFP-positive sorted cells, demonstrating efficient and precise genome editing within the enriched population. Because PBMCs are not disease-relevant corneal epithelial cells and only genomic endpoints were assessed, the clinical applicability of this study is limited and the work should be considered a technical proof-of-concept. This framework supports optimization of CRISPR-based strategies prior to studies in biologically relevant corneal models. 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

Background/Objectives: Collagen hydrolysates are widely used as nutritional ingredients for skin and joint health; however, growing evidence indicates that collagen may also exert beneficial effects on cardiometabolic pathways. Short peptides have been shown to modulate angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV), key regulators of blood pressure and glucose homeostasis. This study aimed to assess the dual ACE- and DPP-IV inhibitory and GLP-1 stimulation activities, respectively of a tripeptide-enriched formulation (CH). The study was performed using a benchmark collagen hydrolysate (BCH) as reference. Methods: ACE and DPP-IV inhibitory activities were evaluated using in vitro enzymatic assays. Cellular compatibility and in situ DPP-IV inhibition were assessed in Caco-2 intestinal cells, while glucagon-like peptide-1 (GLP-1) secretion was measured in STC-1 enteroendocrine cells. The degree of hydrolysis was determined by OPA assay, and nanoLC–HRMS was used to characterize and compare the proteomic profiles of the samples. Results: Both hydrolysates exhibited dose-dependent ACE and DPP-IV inhibition; however, CH showed significantly higher inhibitory activity at comparable concentrations. CH also reduced cellular DPP-IV activity in Caco-2 cells and stimulated GLP-1 secretion in STC-1 cells, whereas BCH showed limited or non-significant cellular effects. Peptidomic analysis revealed an enrichment of short- and medium-length peptides in CH, while BCH contained a higher proportion of long peptides (>2000 Da). Consistently, CH exhibited a 1.7-fold higher degree of hydrolysis than BCH. Conclusions: The tripeptide-enriched collagen hydrolysate demonstrated superior enzymatic and cellular bioactivity compared with the benchmark formulation, supporting its potential as a multifunctional bioactive ingredient for health applications. 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

Background: Phenothiazine derivatives bearing trifluoromethyl substituents have attracted increasing interest as multifunctional scaffolds in drug repositioning strategies, particularly in cancer and infectious diseases. Structural modification of classical phenothiazines by incorporation of a quinoline moiety has previously been shown to enhance biological activity. Objectives: The present study aimed to develop an efficient synthesis of 8-trifluoromethylquinobenzothiazines and to evaluate the anticancer and antibacterial potential of their N-substituted analogues inspired by triflupromazine, trifluoperazine, and fluphenazine. Methods: 6H-8-Trifluoromethylquinobenzothiazine was synthesized by cyclization of 2-amino-4-trifluoromethylbenzenethiol and 3-bromo-2-chloroquinoline. The resulting quinobenzothiazine, unsubstituted at the nitrogen atom, was subjected to N-alkylation reactions to afford eleven new 6-dialkylaminoalkyl derivatives. Structural elucidation was performed using NMR and HRMS techniques. Anticancer activity was evaluated by MTT assay against human breast (MDA-MB-231), pancreatic (Mia-PaCa-2), and lung (A-549) carcinoma cell lines, as well as normal HaCaT keratinocytes. Antibacterial activity was assessed by MIC/MBC determination against selected Gram-positive and Gram-negative reference strains and clinical isolates. Results: Among the synthesized compounds, derivatives 8 and 12 exhibited the most favorable anticancer profiles, showing micromolar cytotoxicity (IC₅₀ ≈ 4–10 µM) against lung and pancreatic cancer cells combined with moderate selectivity toward cancer cells over normal keratinocytes. Compound 6 displayed lower cytotoxic potency but a notably high selectivity index due to minimal toxicity toward normal cells. In antibacterial assays, compound 3 exhibited activity against Gram-positive bacteria, including a methicillin-resistant Staphylococcus aureus isolate, with MIC values ranging from 7.8 to 15.6 µg/mL. The corresponding MBC values were equal to or twofold higher than the MICs (MBC/MIC = 1–2), fulfilling commonly accepted criteria for bactericidal activity (MBC/MIC ≤ 4). OD-based growth kinetics confirmed concentration-dependent inhibition of S. aureus growth. Conclusions: The obtained results identify 8-trifluoromethylquinobenzothiazines as a promising class of multifunctional compounds. Selected derivatives combine anticancer activity with acceptable selectivity or display potent antibacterial effects against clinically relevant Gram-positive pathogens. Full article