Search Results (392)

Background: Tendinopathy remains a prevalent musculoskeletal disorder with limited disease-modifying pharmacotherapy. This study aimed to identify a reparative agent from the traditional medicinal herb Eucommiae Cortex and elucidate its mechanism of action. Methods: A bioactive fraction was first identified through a bioactivity-guided strategy using tenocyte cytoprotection and migration assays, then characterized by UHPLC-HRMS/MS. Its major constituent, aucubin (AU), which mirrors the fraction’s key pharmacological activities, was evaluated both in vitro and in vivo. In H₂O₂-injured tenocytes, AU’s effects on viability, apoptosis, oxidative stress (ROS, MDA, SOD) and inflammation (IL-1β, TNF-α) were assessed, with specific focus on estrogen receptor (ER) pathway involvement using pharmacological tools (17β-estradiol and (R, R)-THC). In a collagenase-induced Achilles tendinopathy model using male SD rats, AU’s therapeutic efficacy was evaluated via multimodal assessment: ultrasonography, histopathology (H&E, Masson’s trichrome, Sirius red), TEM, immunohistochemistry, and biochemical analysis of tissue markers. Results: AU effectively attenuated H₂O₂-induced tenocyte injury by enhancing viability, reducing apoptosis, and mitigating oxidative/inflammatory stress. These effects were mimicked by 17β-estradiol and reversed by the selective ERβ antagonist (R, R)-THC, indicating ERβ dependence. In vivo, AU treatment promoted structural and functional recovery, improved collagen maturity (increased Col I/Col III ratio and fibril diameter), suppressed matrix degradation (MMP-3, MMP-13) and apoptosis, and reduced oxidative stress and inflammation in tendon tissue. Conclusions: This study identifies aucubin as a novel phytoestrogenic compound from Eucommiae Cortex that promotes tendon repair through an ERβ-mediated mechanism. These findings position ERβ activation as a promising therapeutic strategy for tendinopathy and highlight AU as a promising lead compound for further development. Full article

Background/Objectives: The rise in antimicrobial resistance is one of the major challenges to global health systems, which necessitates the development of new antibacterial compounds. The bioactive compounds of brown seaweed Sargassum duplicatum have demonstrated potential antibacterial activity. This study applied metabolomic profiling and molecular networking in combination with antibacterial screening assays to assess the antimicrobial properties of S. duplicatum extracts against multidrug-resistant bacteria. Methods: Two extraction methods, i.e., maceration and microwave extraction, were used. Therewith, untargeted metabolomic profiling was performed using Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS). Molecular networks (MNs) were established and compound dereplication was conducted using the spectral database of the Global Natural Products Social Molecular Networking platform (GNPS). Additionally, antimicrobial assays were conducted against Gram-positive and Gram-negative bacterial strains, including multidrug-resistant bacteria, i.e., methicillin-resistant Staphyloccocus aureus ATCC 33592 (MRSA) and β-lactamase, producing Escherichia coli ATCC 35218 (TEM-1 positive strain). Result: Dereplication resulted in the prediction of six compounds with reported antimicrobial properties, i.e., 13-docosenamide, 9-octadecenamide, pheophorbide A, ouabain, sarmentoside B and AC1L1X1Z. Antibacterial screening of the extracts revealed that the ethyl acetate maceration extracts exhibited the strongest inhibitory activity, with inhibition values between 85 and 98% against S. aureus ATCC 33592. Conclusions: This metabolomics study requires further research to isolate, purify, confirm, and validate the dereplicated compounds that may have potential antibacterial activity. Full article

Background: Chronic nonbacterial prostatitis (CNP), the major subset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), imposes a substantial global burden yet lacks satisfactory therapies. Maizibizi Wan (MZBZ) has long been used clinically for prostatitis, but its pharmacodynamic substance basis and mechanisms remain unclear. Methods: Ultra-high-performance liquid chromatography–Q-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) coupled with Global Natural Products Social Molecular Networking (GNPS) molecular networking profiled MZBZ constituents and rat plasma–exposed prototype components and metabolites was used. Based on blood-absorbable components, network pharmacology predicted core targets/pathways; representative interactions were validated by molecular docking. A λ-carrageenan–induced CNBP rat model underwent histopathology (H&E), serum cytokine assays (TNF-α, IL-1β, IL-6/IL-17), immunohistochemistry (COX-2, TNF-α, MMP-9), and Western blotting (P-p65/p65, p-AKT/AKT, COX-2, TGF-β1, BCL2). Results: A total of 188 chemical constituents were identified in MZBZ (79 flavonoids, 38 organic acids, 30 alkaloids, 15 phenylpropanoids, 7 steroids, 4 phenylethanoid glycosides, 15 others). A total of 35 blood-absorbable components (18 prototype components, 17 metabolites) were identified, mainly involving Phase I oxidation and Phase II glucuronidation/sulfation. Network analysis yielded 54 core targets enriched in NF-κB and PI3K/AKT signaling and apoptosis. Docking indicated stable binding of key flavonoids to COX-2, NFKB1, TNF, IL-6, and BCL2. In vivo, MZBZ ameliorated prostatic inflammation, reduced serum TNF-α/IL-1β/IL-6/IL-17 (p < 0.05 or p < 0.01); decreased P-p65/p65, p-AKT/AKT, COX-2, and TGF-β1; and increased BCL2 in prostate tissue. Conclusions: MZBZ exerts anti-CNBP effects via multi-component synergy (prototypes + metabolites) that suppresses inflammatory cytokines, modulates apoptosis, and inhibits NF-κB and PI3K/AKT pathways. These findings provide a mechanistic basis and quality control cues for the rational clinical use of MZBZ. Full article

This study investigated the effect of superheated steam (SS) assisted glycosylation modification on the flavor profile of oyster peptides (OP), and explored the correlation between key flavor compounds and glycosylation degree using Gas Chromatography–Ion Mobility Spectrometry (GC-IMS) and nano-scale Liquid Chromatography coupled with High-Resolution Mass Spectrometry (nano-LC/HRMS). The results indicated that SS treatment accelerated the glycosylation process, reduced free amino groups level, and distinguished their unique flavor through E-nose. GC-IMS analysis detected 64 signal peaks including 13 aldehydes, 6 ketones, 7 esters, 6 alcohols, 2 acids, 2 furans and 5 other substances. And it was revealed that SS-mediated glycosylation treatment reduced the levels of fishy odorants like Heptanal and Nonanal, while promoting the pleasant-smelling alcohols and esters. In addition, Pearson correlation showed a positive correlation between excessive glycation and the increase in aldehydes, which might cause the recurrence of undesirable fishy notes. Further nano-LC/HRMS analysis revealed that arginine and lysine acted as the main sites for glycosylation modification. Notably, glycosylated peptides such as KAFGHENEALVRK, DSRAATSPGELGVTIEGPKE, generated by mild SS treatment could convert into ketones and pyrazines in subsequent reactions, thereby contributing to overall sensory enhancement. In conclusion, SS treatment at 110 °C for 1 min significantly improved the flavor quality of OP and sustains improvement in subsequent stages, providing theoretical support for flavor optimization of oyster peptides. Full article

Maternal undernutrition remains a major modifiable risk factor for adverse pregnancy outcomes. Dietary supplements are widely used to bridge nutritional gaps, but their efficacy, safety, and quality control remain controversial. This review critically evaluates the mechanisms, clinical evidence, and quality assurance of key supplements (folic acid, iron, vitamin D, calcium, iodine, omega-3 PUFA, choline, and multiple micronutrients) specifically in pregnant and postpartum women. We highlight that while folic acid (400–800 µg/d) and iron supplementation reduce neural tube defects by >70% and maternal anaemia by 30–50%, respectively, high-dose antioxidant cocktails (vitamins C + E) have shown no benefit and potential harm in large RCTs. Up to 18–40% of commercially available prenatal supplements contain undeclared pharmaceuticals, heavy metals, or incorrect dosages, underscoring the urgent need for advanced analytical methods (LC-MS/MS, HRMS, NMR). We propose the GAPSS (Genotype–Analytics–Physiology–Safety–Sustainability) framework for future personalised maternal nutrition. Rigorous, pregnancy-specific quality control combined with biomarker-guided supplementation is essential to maximise benefits and minimise risks. Full article

Objectives: Combining two pharmacophores into one molecule with multiple applications presents interest in the field of medicinal chemistry. Quinazolinones are among privileged scaffolds due to their wide biological activities, whereas hydrazones are versatile linkers with pharmacological potential. Thus, this article focused on a green method for the synthesis of new N-acyl-hydrazones of 2-(2-methyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide and the exploration of their biological potential. Methods: The novel N-acyl-hydrazones (1a–1f) were synthesized under microwave irradiation, using various substituted salicylaldehydes and benzaldehydes. The products were characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and HRMS. Their pharmacological profile was assessed by in silico methods and docking simulations. Biological evaluation included antioxidant, antimicrobial, and cytotoxic activities, as well as preliminary toxicity on Artemia franciscana. Results: Spectroscopic data indicated syn-E and anti-E isomers. Compound 1c showed the highest antioxidant activity. Antimicrobial assays indicated narrow-spectrum activity, with compounds 1a and 1b being most effective against C. albicans and S. aureus. Biofilm inhibition assays revealed that 1a and 1c interfered with microbial adhesion, highlighting their potential in combating biofilm-associated infections. Cytotoxicity tests on HT-29 and A431 cancer cell lines showed selective anticancer effects for compounds 1a–1d, with minimal toxicity on normal Vero cells, especially for 1b and 1d. Toxicity against Artemia franciscana correlated with in vitro cytotoxicity data, revealing low lethality for all N-acyl-hydrazones. Docking studies indicate that the antibacterial activity may involve inhibition of S. aureus DNA gyrase B, whereas the cytotoxic effects could be mediated by interaction with the EGFR kinase. Conclusions: These findings may increase the chances of identifying a lead compound in this class, supporting the further development of selected N-acyl-hydrazones and their pharmacological exploration. Full article

Communication and writing skills are critical for employability and leadership in sustainability and STEM fields, but few studies examine how interdisciplinary, problem-based learning (PBL) environments foster these competencies amongst undergraduates. This three-year study examined how human resource management (HRM) and Chemistry students collaborated on Sustainable Development Goal (SDG)-themed projects within a Global Classroom model. We used LIWC-22, a validated text analysis tool to assess students’ written reflections about their discipline-specific PBL exercises (e.g., debates about UBI) and their SDG-focused inter-disciplinary group projects (e.g., vaccine access). We found that the HRM students (n = 84) demonstrated increased use of curiosity and cognition language during in-person and synchronous collaboration contexts. Chemistry students collaborating synchronously with their HRM teammates exhibited enhanced curiosity in their writing, though findings for this group are tentative due to the small sample size. Our findings suggest that both discipline-specific and SDG-focused interdisciplinary PBL activities can improve undergraduates’ metacognitive skills and their curiosity, which are critical for addressing sustainability challenges. Our Global Classroom offers a scalable model of how SDG-focused PBL activities can be used to create collaborations between STEM and management undergraduates and enable them to develop context-specific solutions for global sustainability challenges while improving their communication and writing. Full article

Cucumis metuliferus E. Mey or kiwano/African horned melon is a good source of bioactive compounds of various pharmacological and industrial importance. This study investigated metabolomic shifts in in vitro cultivated kiwano plants over ten weeks of maturity time through GC-MS and LC-HRMS-MS untargeted analysis of volatile and non-volatile metabolites. Furthermore, in silico screening of the highly abundant volatile compounds from each sample was performed against three different proteins and enzymes of Candida spp. These results obtained from GC-MS and LC-HRMS-MS analysis highlight the potential of in vitro culture for enhancing the biosynthetic potential of C. metuliferus for sustainable and controlled production of target metabolites. Furthermore, this work also highlights the potential inhibitory properties of abundant volatile compounds in each stage of maturation period of C. metuliferus, providing a platform for further exploration of the therapeutic applications of C. metuliferus metabolites against Candida spp. Full article

Chirality remains the most neglected axis of pesticide residue science. Many active ingredients are sold as racemates although their enantiomers differ in potency, persistence, transport, and toxicology; as a result, total concentration is a poor surrogate for risk. This review synthesizes green and enantioselective strategies spanning the full analytical–remediation continuum. We survey solvent-minimized sample preparation approaches (SPME/TF-SPME, FPSE, µSPE, DLLME with DES/NADES), MS-compatible chiral separations (immobilized polysaccharide CSPs in LC and SFC, cyclodextrin-based selectors in GC, CE/CEC), and HRMS-enabled confirmation and suspect screening. Complex matrices (e.g., fermented beverages such as wine and high-sugar products) are critically discussed, together with practical matrix-tolerant workflows and the complementary role of chiral GC for hydrophobic residues. We then examine emerging enantioselective materials—MIPs, MOFs/COFs, and cyclodextrin-based sorbents—for extraction and preconcentration and evaluate stereoselective removal via adsorption, biodegradation, and chiral photocatalysis. Finally, we propose toxicity-weighted enantiomeric fraction (EF) metrics for decision-making, outline EF-aware green treatment strategies, and identify metrological and regulatory priorities (CRMs, ring trial protocols, FAIR data). Our thesis is simple: to reduce hazards efficiently and sustainably, laboratories and practitioners must measure—and manage—pesticide residues in the chiral dimension. Full article

Background/Objectives: We conducted an untargeted metabolomic study in serum, urine, and fecal water in colorectal cancer (CRC) patients compared to healthy controls. The aim was to define the interactions between metabolites and microbiota. Methods: Effluents were collected before colonoscopy. Metabolites were analyzed using LC-HRMS. Bioinformatics analyses included Limma test, along with spectral house and public databases for annotations. Whole-genome shotgun sequencing was performed on fecal samples. Species–metabolite interactions were calculated using Spearman correlation. Interleukins and inflammatory proteins were measured. Results: Fifty-three patients (11 stage I, 10 stage II, 10 stage III, and 22 stage IV) and twenty controls were included. Derivatives of deoxycholic acid, cholic acid, and fatty acids were lower in serum, while urinary bile acids were higher in stage IV CRC patients (versus controls). Metabolites related to tryptophan and glutamate were found significantly altered in stage IV: upregulation of kynurenine and downregulation of indole pathways. This was linked to increased inflammatory protein and microbial metabolites and to the imbalance between virulent pro-inflammatory bacteria (Escherichia and Desulfovibrio) and symbiotic (Ruminococcus and Bifidobacterium) bacteria. Conclusions: E. coli-related tryptophan catabolism shift is shown through stage IV CRC as compared to controls. As a consequence, tryptophan/kynurenine metabolite may become a promising marker for detecting the failure to immune response during therapy. Full article

In our continuing search for new anticancer and/or antimicrobial compounds from natural products, we screened for these activities in bark and leaf extracts of sandalwood plants collected from the Fiji Islands and found Santalum yasi to be the most active. Resulting chemical workup enabled the isolation and structural characterization of a new acetylenic acid, methyl (E)-octadec-6-en-8-ynoate (1), and an atropisomeric stilbene glycoside (4) (Yasibeneoside) together with six known compounds: 11,13-octadecadien-9-ynoic acid (2), methyl octadeca-9,11-diynoate (3), gaylussacin (5) chrysin-7-beta-monoglucoside (6), neoschaftoside (7), and chrysin-6-C-glucoside-8-C-arabinoside (8). Compound 1 (18:2 (6t, 8a) is an example of a Δ⁶, Δ⁸ acetylenic system containing the trans double bond at C-6 and the triple bond at C-8, which is reported here for the first time. All molecular structure elucidations and dereplications were performed using spectroscopic techniques, including 2D NMR and HRMS-MS/MS spectrometry. Methyl (E)-octadec-6-en-8-ynoate showed moderate activity activity with an IC₅₀ of 91.2 ug/mL against the human breast adenocarcinoma cell line MCF-7. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by cholinergic dysfunction, oxidative/nitrosative stress, and neuroinflammation. Marine green algae Caulerpa racemosa are rich in neuroactive lipids and fatty acid derivatives with reported antioxidant and anti-inflammatory properties. However, their integrated mechanistic potential against AD remains largely underexplored. This study aimed to elucidate the neuroprotective mechanisms of C. racemosa metabolites against AD using integrative metabolomics, network pharmacology, molecular docking, and in vitro validation assays. Untargeted LC–HRMS profiling was performed to identify major metabolites in the ethanolic extract of C. racemosa. Neuroprotective targets were predicted via TargetNet, STRING, and Cytoscape (MCODE, CytoNCA). Functional enrichment was conducted using KEGG, GO (BP, MF, CC), and ClueGO. Molecular docking (CB-Dock2) validated compound–target interactions with ACHE, CHRM1, NOS1, and NOS2. Antioxidant (DPPH) and cholinesterase (AChE/BChE) inhibitory activities were evaluated in vitro. Metabolomic profiling identified lipid-dominant metabolites—oleamide, hexadecanamide, palmitoyl ethanolamide, α-linolenic acid, α-eleostearic acid, and 9-oxo-octadecadienoic acid. Network analysis revealed key AD-related hubs (ACHE, CHRM1, NOS1, NOS2) enriched in cholinergic regulation, arachidonic-acid metabolism, oxidative stress response, and nitric oxide signaling. Docking showed moderate multi-target affinities (−6.0 to −8.4 kcal/mol), with α-linolenic acid, α-eleostearic acid, and oxidized C18 lipids exhibiting the strongest interactions—particularly with ACHE and NOS isoforms. In vitro assays showed moderate antioxidant activity (IC₅₀ = 120.97 ± 10.93 µg/mL) and cholinesterase inhibition (AChE IC₅₀ = 136.48 ± 1.70 µg/mL; BChE IC₅₀ = 145.98 ± 3.28 µg/mL), aligning with predicted multi-target interactions. C. racemosa extract exhibits neuroprotective potential through a synergistic combination of cholinergic modulation, antioxidant activity, NOS-mediated nitrosative stress reduction, and suppression of arachidonic-acid inflammatory pathways. These findings support C. racemosa as a promising marine-derived multi-target candidate for AD intervention, warranting further mechanistic and in vivo evaluation. Full article

Background/Objectives: Land management practices strongly influence soil biochemical processes, yet conventional soil measurements often overlook dynamic small-molecule variation underlying nutrient cycling and microbial activity. This study aimed to evaluate whether MS¹-based untargeted metabolomics can resolve meaningful biochemical differences among soil systems under distinct land management practices. Methods: Soils from six land-use types—conventional cultivation, organic cultivation, pasture, white pine, tulip poplar, and hardwood forest—were analyzed using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Multivariate analyses, including PLS-DA, were performed to evaluate metabolic variation across systems. Both identified metabolites and unknown spectral features (MSI Level 4) were assessed, and biosynthetic class assignment of unknown features was performed using NPClassifier. Results: Metabolic features revealed clear separation between land management systems, demonstrating distinct chemical fingerprints across ecosystems. While conventional elemental ratios (e.g., C/N) showed minimal differentiation, phosphorus-related stoichiometric ratios (C/P and N/P) displayed strong land-use-dependent differences. NPClassifier superclasses highlighted unique chemical patterns, with forest soils enriched in diverse secondary metabolites, cultivated soils characterized by simplified profiles, and pasture soils dominated by microbial membrane lipids and alkaloids. Conclusions: Untargeted MS¹-based metabolomics effectively distinguished soil systems under different land-use practices and revealed ecologically meaningful variation even without complete structural identification. This study demonstrates that an MS¹-only workflow leveraging unknown spectral features can robustly distinguish soil systems, underscoring their value in untargeted metabolomics analyses. Full article

Antarctic algae have evolved in extreme environmental conditions, developing unique metabolic adaptations with significant biotechnological potential. In this study, we explored the bioactivity of the sea-ice microalga Microglena antarctica by preparing acetone and methanol extracts from biomass cultivated at 4, 8, and 16 °C. These extracts were screened for their in vitro antioxidant properties and inhibitory activities on enzymes related to Alzheimer’s disease (acetylcholinesterase: AChE, butyrylcholinesterase: BChE), type 2 diabetes mellitus (T2DM, α-glucosidase, α-amylase), obesity (lipase), and hyperpigmentation (tyrosinase). Our screening revealed a high capacity of acetone extracts to scavenge the ABTS•⁺ radical (EC₅₀ ranging from 3.57 to 4.18 mg mL⁻¹), along with strong copper chelating activity in both acetone and methanol extracts (EC₅₀ values of 6.31 and 6.41 mg mL⁻¹). Relevant inhibition towards α-amylase (IC₅₀ values of 3.34 and 4.53 mg mL⁻¹) and tyrosinase (with IC₅₀ ranging from 3.82 to 5.47 mg mL⁻¹) was reported for acetone and methanol extracts, respectively. UHPLC-HRMS-based profiling revealed the presence of lipidic molecules, such as glycolipids, phospholipids, and betaine lipids with polyunsaturated carbon chains, together with carotenoids, including canthaxanthin and adonixanthin, which are likely responsible for the observed bioactivities. Full article

In this paper, we present enabling concepts for Zero Defect Manufacturing (ZDM) based on flexible human–robot interaction. We introduce the Human–Robot Multistation System (HRMS) as a novel framework for flexible, human-initiated task allocation across multiple workstations. A HRMS is defined as one or more workstations that support human–robot collaborative task execution and integrate intelligent perception and interaction systems with coordination logic, enabling alternating or collaborative task execution. These components allow human workers to interact with the system through a gesture-based modality and to receive task assignments. An agent-based task scheduler responds to human-initiated ‘Ready’ signals to pace activities ergonomically. We built a laboratory demonstrator for an Industry 5.0 ZDM final inspection/rework use case and conducted a first pilot study (n = 5, internal participants) to evaluate system usability (SUS), perception (Godspeed), mental workload (NASA-TLX), completion times, and error rates. Results indicated technical feasibility under laboratory conditions and acceptable usability, with SUS 70.5 ± 22 (‘OK’ toward ‘Good’), overall GQS 3.2 ± 0.8, RAW NASA-TLX 37 ± 16.3, mean job throughput time 232.5 ± 46.5 s, and errors in 9/10 jobs (E1–E4). In simulation, a proximity-aware shortest-path heuristic reduced walking distance by up to 70% versus FIFO without productivity loss. We conclude that HRMS is feasible with acceptable user experience under lab constraints, while recurrent task-level failures require mitigation and larger-scale validation. Full article