Search Results (4,629)

Animal welfare monitoring is essential in pig production. On-farm animal welfare (AW) assessments may provide a comprehensive overview but are resource-intensive. Abattoir-based assessments allow pigs from multiple farms to be inspected in a single facility. However, data on the relationship between these assessments remain limited, especially for heavy pigs (160–170 kg). This study investigates these associations in Italian heavy pig production. At the abattoir, 18,333 pig carcasses from 185 batches across 86 farms were scored for tail, skin (cranial and caudal) and ear lesions. On-farm AW assessments (management, structures and animal-based measures) were obtained from the national surveillance system (ClassyFarm). Tail lesion scores were higher in pigs with intact tails, whereas ear scores showed the opposite trend, suggesting a substitution effect between tail and ear biting. This indicates that tail docking is insufficient to fully prevent abnormal behaviours. Higher skin and ear scores were associated with suboptimal management, but tail scores were not, likely due to the multifactorial nature of tail biting. Herd size had no significant effect on welfare indicators. These results highlight the complexity of assessing AW and the importance of combining abattoir and farm data to obtain a more integrated monitoring system. Full article

The emergence of variant strains of Avian orthoreovirus (ARV) has caused substantial economic losses in the poultry industry worldwide, but the molecular features of goose-origin strains and viral transmission among different avian species remain poorly understood. Here, we describe a goose-origin avian orthoreovirus strain, SD0407, associated with growth retardation and joint swelling. Complete genome analysis identified ten double-stranded RNA segments. Sequence comparison indicated that SD0407 is closely related to previously reported duck-origin reovirus strains. Phylogenetic and recombination analyses showed that most segments clustered with duck-origin strains, indicating close genetic relatedness among waterfowl-origin orthoreoviruses. Sequence and structural analysis of the σC attachment protein revealed ten unique amino acid substitutions, including D250 within the DE-loop region involved in receptor-binding. Molecular docking suggested that σC interacts with the conserved AnxA2-S100A10 heterotetrameric receptor complex, providing a possible structural basis for receptor compatibility across avian species. Although SD0407 replicated efficiently in goose embryo fibroblasts, it did not induce expression of type I, II or III interferons. Transcriptome profiling revealed weak activation of innate immune signaling and downregulation of metabolic and cytoskeletal genes, consistent with effective suppression of antiviral responses. These findings demonstrate that SD0407 combines structural variability with immune evasion to enhance host adaptability and underscore the importance of sustained ARV surveillance in waterfowl populations. Full article

A new series of eight novel etodolac-based 1,3,4-oxadiazoles was synthesized, characterized, and tested in silico in multidimensional routes, starting with etodolac, a well-known nonsteroidal anti-inflammatory medication (NSAID). In silico studies were performed prior to synthesis using the molecular docking technique in CCDC GOLD suite software (2025.3) to assess the interactions with two key targets involved in cancer pathogenesis: the crystal structure of the epidermal growth factor receptor EGFR tyrosine kinase domain (PDB ID: 4HJO) and the matrix metalloproteinase (MMP-9) complex (PDB ID: 5CUH). ADME studies were performed to assess the physicochemical properties of the synthesized molecules. Importantly, biotransformation prediction also indicated that the derivatives possess high metabolic stability, with hydroxylation of the thio-ether group as the primary predicted biotransformation route. All compounds were characterized using melting point, FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopy. In vitro and/or in vivo experiments are needed to confirm this preliminary anticancer study. Full article

Background/Objectives: Curcumin derivatives have attracted interest due to their redox-modulating properties and potential applications in aquatic organisms, yet their molecular interactions and environmental safety remain insufficiently characterized. This study aimed to evaluate the redox-related molecular behavior and ecotoxicological profile of curcumin derivatives, with emphasis on their interaction with glutathione S-transferase from L. vannamei. Methods: Molecular docking and molecular dynamics simulations were performed to assess binding stability and interaction patterns between the derivatives and LvGSTmu. In parallel, computational predictions were used to estimate environmental persistence, bioaccumulation (BCF/BAF), and acute and chronic aquatic toxicity across multiple trophic levels. Results: Docking and dynamics analyses indicated stable ligand–protein interactions, particularly for CURNO, which showed favorable binding behavior without destabilizing the protein structure. Ecotoxicological predictions suggested low bioaccumulation potential and limited persistence for most derivatives, with CURH and CURNO showing higher sediment persistence. Toxicity responses varied by organism and exposure time but did not differ significantly among derivatives relative to curcumin. Conclusions: The derivatives retained redox-related molecular features while presenting an overall acceptable predicted environmental profile. CURNO emerged as a promising candidate, although its environmental behavior supports the need for further monitoring and experimental validation. Full article

Background: The ability of synthetic plastics to persist in the environment and the accumulation of microplastics has intensified the need to explore biological mechanisms capable of interacting with, and possibly degrading, polymeric materials. Microbial enzymes that have extensive catalytic flexibility represent promising candidates in this context. Aim: This study set out to examine the molecular interaction patterns and dynamical stability of Pseudomonas aeruginosa elastase (LasB) with representative structural fragments of typical synthetic plastics to assess the suitability of the enzyme to polymer-derived substrates. Methods: The crystallographic structure of LasB (PDB ID: 1EZM) was retrieved from the Protein Data Bank and pre-prepared with the help of AutoDock4.2.6 Tools. Those polymer-derived ligands that were associated with the major industrial plastics such as polyamide (PA), polyvinyl chloride (PVC), polycarbonate (PC), poly-ethylene terephthalate (PET), polymethyl methacrylate (PMMA), and polyurethane (PUR) were retrieved in the PubChem database and geometrically optimized with the help of the MMFF94 force field. AutoDock Vina, with a specific grid box around the catalytic pocket, including Zn²⁺ ion, was used to perform molecular docking simulations. PyMOL and BIOVIA Discovery Studio software were used to analyze binding conformations, interaction residues and types of intermolecular contacts. Phosphoramidon, a known metalloprotease inhibitor, served as a positive control to confirm the docking protocol. Additional assessment of the structural stability and conformational behavior of the enzyme–ligand complexes was conducted by molecular dynamics (MD) simulations with the Desmond engine and explicit solvent model in a 50 ns trajectory using the OPLS4 force field. RMSD, RMSF, radius of gyration, hydrogen bonding analysis and solvent accessibility parameters were used to measure structural stability. Results: The docking experiment showed varying binding affinities with the test polymers. Polycarbonate (−5.774 kcal/mol) and polyurethane (−5.707 kcal/mol) had the highest in-teractions with the LasB catalytic pocket, polyamide (−5.277 kcal/mol) and PET (−4.483 kcal/mol) followed PMMA and PVC, which had weaker affinities. The following were the important residues involved in interaction networks: Glu141, His140, Val137, Arg198, Tyr114, and Trp115 that were implicated in interaction networks with hydrophobic interactions, π-cation interactions and van der Waals forces that were the major stabilization forces. MD simulations had stabilized complexes, and RMSD values were found to be within acceptable ranges of stability, and ligand-specific changes (around 1.0-3.2 A), which is also in line with stable protein-ligand systems. Phosphoramidon used as a positive control had an RMSD of 1.205 A which is within this stability range. PCA determined various ligand-bound conformational states of LasB with PA in com-pact state, PC and PVC in intermediate states and PUR, PMMA and PET in ex-panded conformations, indicating structur-al stability and adaptability of the binding pocket. Conclusion: These findings show that LasB has a structurally flexible catalytic pocket that can accommodate a wide range of polymer-derived ligands. These results offer an insight into the recognition of enzymes with polymers at the molecular level and also indicate that LasB might help in the interaction of microorganisms with synthetic plastics in environmental systems. Full article

Background/Objectives: Poly(ADP-ribose) polymerase 1 (PARP1) is an important therapeutic target in DNA repair-deficient cancers, but discovery of new inhibitors remains constrained by scaffold convergence, tolerability limits, and acquired resistance. This study aimed to develop an interpretable, reliability-stratified cheminformatics workflow for PARP1 potency prioritization and structure-based follow-up. Methods: A curated ChEMBL dataset of 3339 PARP1 inhibitors was encoded using RDKit 2D descriptors and Avalon fingerprints (1143 initial features), then reduced to 132 informative variables by Random Forest-based feature selection. Five regression models were optimized, including a stacked ensemble. Model interpretation was performed using permutation feature importance and SHAP. External near-domain corroboration was assessed using a stringent PubChem similarity expansion (Tanimoto > 0.90) around sub-10 nM seed compounds, followed by comparison with retrievable experimental PARP1 activity values. Top scaffold-diverse candidates were further evaluated by complementary docking against PARP1 (PDB: 4R6E) using AutoDock Vina and cavity-guided docking through the SwissDock platform. Results: The stacked ensemble achieved the best held-out performance (test R² = 0.723; RMSE = 0.610 pIC₅₀ units), with 83.7% of test predictions within ≤0.75 pIC₅₀ units and only 2.7% exceeding 1.5 pIC₅₀ units. PubChem similarity expansion retrieved approximately 32,450 analogs, of which 3349 were predicted to have IC₅₀ ≤ 10 nM. Among 366 compounds with retrievable experimental PARP1 activity values, predicted versus experimental pIC₅₀ showed a positive association (R² = 0.124; Pearson r = 0.479), with RMSE = 0.491 and MAE = 0.330 pIC₅₀ units. Three ligands—CID 168873053, CID 175154210, and CID 172894737—showed the strongest complementary docking support and pocket-consistent poses relative to niraparib. Conclusions: This workflow provides a transparent and practically useful framework for near-domain PARP1 inhibitor prioritization. The combined QSAR, explainability, external corroboration, and docking strategy supports shortlist generation for experimental follow-up. Full article

Sanghuangporus vaninii (Ljub.) is an edible and medicinal macrofungus that has become the main strain for artificial cultivation of Sanghuang. In this study, twenty-six compounds (1–26), including five previously undescribed ergosterols, named sanghusterols A–E (1–5), were isolated from the fruiting bodies of S. vaninii. Their structures were elucidated by spectroscopic methods and electronic circular dichroism (ECD) calculations. Compounds 1, 15, 17, 21 and 25 exhibited potent inhibitory activity against NO production with the IC₅₀ value of 8.3–14.8 μM and dose-dependently decreased iNOS and COX-2 protein expression in RAW264.7 cells. Molecular docking studies confirmed the capacity of compounds 1, 15, 17, 21 and 25 to interact with iNOS and COX-2 proteins. These findings may provide a solid phytochemical and pharmacological basis for developing the mushroom as potential anti-inflammatory agents. Full article

Molecular docking is a foundational technique in computational drug discovery, widely used to generate binding hypotheses, prioritize compounds, and support target-selectivity studies. The continued growth of open-source docking resources, together with improvements in scoring functions, sampling strategies, and hardware acceleration, has substantially lowered barriers to teaching, early-stage hit identification, and reproducible research. Beyond standalone docking engines, the open-source ecosystem now encompasses browser-accessible tools, preparation and analysis utilities, integrative modeling platforms, and AI-augmented methods for pose prediction, rescoring, and virtual screening. These developments have made docking workflows more accessible, customizable, and transparent across diverse research settings. This review examines open-source docking from a workflow-centered perspective, spanning study design, structural-data acquisition, binding-site definition, receptor and ligand preparation, docking execution, and post-docking validation. It further evaluates how open AI methods are being incorporated into these stages to expand structural coverage, improve screening efficiency, and support contemporary structure-based drug design. Collectively, this review outlines a practical and evidence-based framework for the effective use of open-source docking and virtual-screening pipelines in modern drug discovery. Full article

Chrome tanning of fish skins generates hazardous effluents and carcinogenic Cr(VI) residues; chromium-free routes to valorize collagen-rich by-products from aquaculture and coastal fisheries are therefore needed. We report a 12-stage ecological protocol employing acetic acid/NaCl pickling, Acacia mearnsii tannin, A. podalyriifolia retanning, mashed-papaya enzymatic bating, and cinnamon as antimicrobial/odor adjunct, scaled from bench to pilot using exclusively locally sourced inputs, for Nile tilapia (Oreochromis niloticus) and Patagonian flounder (Paralichthys patagonicus). Three trained operators evaluated macroscopic quality against five predefined criteria adapted from SATRA and ISO 3376 grading conventions, providing a structured feasibility baseline that does not substitute for the standardized instrumental testing designated as priority future work. Both species achieved satisfactory grain stability, complete tannin penetration, pliable handle, and cinnamon-dominant odor without residual amines; dark-brown coloration is a recognized practical limitation for fashion applications. In silico molecular docking (GNINA v1.0) was used to explore the mechanistic plausibility of each ecological substitution, generating testable hypotheses rather than definitive mechanistic conclusions: the multidentate polyphenol proxy (PGG) exhibited consistently superior collagen engagement over the flavanol monomer across both collagen constructs and all three scoring metrics (1CAG: Vina affinity −5.51 ± 0.13 vs. −3.54 ± 0.35 kcal/mol; CNNscore 0.874 ± 0.009 vs. 0.771 ± 0.010; 7CWK: Vina affinity −6.98 ± 1.43 vs. −4.37 ± 0.16 kcal/mol; CNNscore 0.858 ± 0.024 vs. 0.635 ± 0.094). Dipeptide probes were reproducibly accommodated in the papain catalytic cleft, with the closest configuration reaching 3.997 Å from the catalytic nucleophile (OCS25-SG). Trans-cinnamaldehyde occupied the quorum-sensing pocket with reproducible placement (CNNscore 0.718 ± 0.034) but without score-based selectivity over structural decoys, a result interpreted as hypothesis-generating for future microbiological validation. The protocol is reproducible from bench to pilot and generalizable across two species with distinct dermal architectures. Quantitative physical-mechanical testing (shrinkage temperature, tensile strength, elongation, tear load), CIELab colorimetric analysis, and effluent characterization (COD, BOD₅, total phenolics) are designated as priorities for future validation. Full article

Vanillin is widely used in foods, but its poor water dispersibility and limited stability reduce its flavor performance during processing and storage. In this study, soy protein isolate (SPI) was used as a food-grade carrier to prepare soy protein isolate–vanillin (SPIV) complexes via a pH-shifting strategy. SPI and vanillin were first adjusted to pH 9.0, where SPI unfolded and vanillin was deprotonated and dispersed in the solution and then readjusted to pH 7.0 to form SPIV complexes. Vanillin was incorporated into SPI at different loading levels of 0.5, 1.0, 2.5, and 5.0 mg/mL, corresponding to 9–50 wt.% relative to SPI. The binding efficiency of vanillin decreased from 91.03 wt.% to 69.43 wt.% with increasing vanillin loading. Moderate loading preserved the globular morphology of SPI, whereas excessive loading (≥33.33 wt.%) induced vanillin nanocrystal formation and aggregation. Spectroscopic analyses and molecular docking indicated that vanillin interacted with soy proteins through a combination of covalent and noncovalent interactions. Compared with free vanillin, SPIV showed improved color, light, and thermal stability. Among the tested samples, SPIV2 exhibited the most favorable interfacial behavior and application performance, producing more stable emulsions and higher flavor scores in simplified beverage and soy milk models. These findings establish a loading-dependent structure–function relationship in SPIV complexes and provide practical guidance for the design of soy protein-based carriers for flavor stabilization and delivery. Full article

Sulfated peptides, such as PSK, PSY, CIF, and RGF, are crucial regulators of plant growth, development, and stress responses, with their activity dependent on post-translational tyrosine sulfation by tyrosylprotein sulfotransferase (TPST). This study explores the evolutionary history and the interaction mechanisms between TPST and sulfated peptides in plants. Systematic analyses of multi-species genomes show that TPST can be traced back to the chlorophyte lineage, whereas PSK, a sulfated peptide, appears to have emerged in gymnosperms. TPST is evolutionarily conserved, typically present in low copy numbers across plant lineages, while its peptide substrates have expanded in angiosperms. In Liriodendron chinense, TPST-sulfated peptide gene promoters are enriched with cis-regulatory elements linked to abscisic acid, gibberellin responsiveness, and anaerobic induction. Synteny analyses revealed collinearity between sulfated peptide genes in L. chinense, Magnolia biondii, Arabidopsis thaliana, and Populus trichocarpa, but not with Oryza sativa. Molecular docking identified key TPST-PSK interaction sites in the sulfotransferase domain, with several critical residues facilitating binding. Transcriptomic and co-expression network analyses revealed that LcTPST was expressed at lower levels than its peptide precursor genes, while LcPSK2 remained highly expressed after the torpedo stage of somatic embryogenesis. Stress conditions significantly increased PSK-associated module connectivity, enriched in transcription factors such as WRKY, bHLH, bZIP, and MADS. This study provides insights into the evolutionary, structural, and regulatory aspects of the TPST-sulfated peptide system in plants. Full article

Sulfur fumigation, as a highly effective method for preservation and appearance enhancement, has been widely applied in fruits, vegetables, and food products. However, excessive sulfur fumigation can pose safety risks. Currently, there is limited research on the bound sulfites produced by sulfur fumigation, and no consensus has been reached regarding their structure and toxicity. Using ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS), a total of 34 compounds were identified in 12 lily bulb samples subjected to different sulfur fumigation durations. These derivatives were all hypothesized to form via nucleophilic addition to carbon–carbon double bonds. Based on multivariate statistical analysis, 9 characteristic markers were established to rapidly differentiate between non-fumigated (NF) and sulfur-fumigated (SF) samples. The practicality of this strategy was validated using 18 commercial batches. Molecular docking simulations predicted that the modifications might enhance toxicity toward liver injury-related targets, both by altering the spatial conformation of the compounds and because the sulfonic acid group itself serves as an ideal hydrogen-bond acceptor. Overall, mild fumigation led to a gradual accumulation of free sulfur dioxide in lily bulbs, increased the total content of phenolic components and antioxidant capacity, and did not generate excessive bound sulfur dioxide. However, with further extension of fumigation time, the content of sulfur-containing derivatives rose rapidly, accompanied by a noticeable decline in antioxidant activity. This study elucidates the sulfur-driven chemical transformation mechanisms in lily bulbs and establishes a targeted methodology for the quality control and safety assessment of processed herbal products. Full article

Thyroid hormones (THs) and estrogen (E2) play essential roles in neuronal differentiation and plasticity during brain development. S-equol, a plant-derived isoflavone metabolite, is a selective E2 receptor (ER) ligand that exhibits neurotrophic effects; however, its interaction with TH receptor (TR) signaling remains unclear. In this study, we investigated the effects of S-equol on TRβ-associated transcriptional activity and neuronal morphogenesis in mouse neuroblastoma-derived Neuro-2a cells or rat C6 glioma cells. Luciferase reporter assays demonstrated that S-equol significantly enhanced T3-induced TRβ transcriptional activity in a concentration- and time-dependent manner. Additionally, exposure to S-equol or T3 alone promoted neurite outgrowth and wound closure, whereas co-exposure to both compounds resulted in a more significant enhancement of these processes. Furthermore, mRNA expression levels of synapse-related genes (Dlg4, Syn1, Syp, Camk2b, and Bdnf) were significantly increased by S-equol co-exposure in the presence of T3. In silico docking analysis revealed that S-equol exhibited moderate to high binding affinity for TRβ (−8.7 kcal/mol), ERα, and ERβ, suggesting a structural basis for TR–ER crosstalk. Collectively, these findings indicate that S-equol functions as a dual-acting modulator that may modulate T3 signaling involving TR–ER interaction. Although S-equol may exert beneficial effects on neurodevelopment, it may also act as an endogenous endocrine modulator that alters the fine regulation of TH action during development, warranting careful evaluation from physiological and toxicological perspectives. Full article

Excessive alcohol consumption causes millions of deaths annually, yet current pharmacological treatments for alcohol use disorders show limited efficacy and poor adherence, creating an urgent need for new therapeutic alternatives. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde, a key mediator of the rewarding effects of alcohol in the brain, making ALDH2 activation a promising therapeutic target. This study investigated whether flurbiprofen, an FDA-approved nonsteroidal anti-inflammatory drug that activates ALDH2, reduces alcohol intake compared to the experimental ALDH2 activator Alda-1 and the structurally similar NSAID ibuprofen. Male alcohol-preferring UChB rats received oral flurbiprofen (2.5–10 mg/kg), Alda-1 (5 mg/kg), or ibuprofen (5 mg/kg) during acquisition and chronic phases of voluntary alcohol consumption under a two-bottle free-choice paradigm. Both flurbiprofen and Alda-1 reduced alcohol intake by approximately 60% and similarly increased ALDH2 activity 3–4-fold in brain and liver tissues. Ibuprofen showed modest effects (25% alcohol intake reduction). In vitro assays confirmed that flurbiprofen and Alda-1, but not ibuprofen, activated ALDH2 in PC-12 cells. Enzymatic assays and molecular docking revealed that Alda-1 lacks cyclooxygenase-inhibitory activity, unlike flurbiprofen, suggesting that ALDH2 activation is the primary mechanism underlying reduced alcohol consumption. These findings identify flurbiprofen as a clinically available ALDH2 activator with significant translational potential for treating alcohol use disorders. Full article

Aberrant protein glycosylation is a key driver of colorectal cancer (CRC) progression, contributing to tumour growth, metastasis, and immune evasion. In this study, computational approaches were employed to explore the potential of Brefeldin A as an inhibitor of two glycosylation-associated regulatory proteins: Protein Kinase C alpha (PrKCα) and Mitogen-Activated Protein Kinase 1 (MAPK1). Using computational docking and structural analyses, Brefeldin A was predicted to bind effectively to both targets, thereby inhibiting their enzymatic activities. Detailed investigations revealed that Brefeldin A interacts favourably within the active sites of MAPK1 and PrKCα, forming stable complexes by optimal binding interactions. Key residues contributing to binding stabilisation were identified in both MAPK1 and PrKCα. For MAPK1, residues such as Lys114 and Ser153 played a significant role in hydrogen bonding interactions, while for PrKCα, Gln105, Asn154, and Asp167 were notably involved. These interactions included both hydrogen bonds and hydrophobic contacts, which collectively contributed to the strength and specificity of ligand binding. The identification of these residues provides insight into the molecular mechanisms underlying the stabilisation of the Brefeldin A-kinase complexes. Binding affinity estimations showed that Brefeldin A bound to MAPK1 exhibited a binding energy of −22.18 ± 4.50 kcal/mol. In contrast, the Brefeldin A bound to PrKCα demonstrated a slightly stronger binding energy of −23.90 ± 5.36 kcal/mol. Collectively, these findings underscore Brefeldin A’s potential as a novel inhibitor targeting glycosylation-related proteins in CRC, offering a promising therapeutic strategy to impede CRC progression. This work not only proposes Brefeldin A as a promising therapeutic lead but also supports glycosylation inhibition as a valuable approach for CRC control, with broader implications for drug discovery in glycan-related oncogenic pathways. Full article