Search Results (275)

This study used all-atom molecular dynamics simulations to investigate the structural dynamics of Ves a 1, a phospholipase from Vespa affinis venom, and its interactions within a lipid membrane environment, both alone and in the presence of the inhibitor voxilaprevir. Simulations conducted over 1 $\mathsf{\mu }$s for triplicate runs demonstrated system stability and convergence of structural properties. Our findings reveal that Ves a 1 engages in dynamic interactions with the lipid bilayer, involving key regions such as its lids, catalytic triad, and auxiliary site. The presence of voxilaprevir was observed to subtly alter these membrane interaction patterns and influence the enzyme’s catalytic area, reflecting the inhibitor’s impact within its physiological context. These results emphasize the crucial role of the lipid bilayer in shaping enzyme function and highlight voxilaprevir as a promising candidate for further inhibitor development, offering vital insights for rational drug design targeting membrane-associated proteins. Full article

Cold environments challenge the structural and functional integrity of membrane proteins, requiring specialized adaptations to maintain activity under low thermal energy. Here, we investigate the molecular basis of cold tolerance in the peptide transporter PepT1 from the Antarctic icefish (Chionodraco hamatus, ChPepT1) using molecular dynamics simulations, binding free energy calculations (MM/GBSA), and dynamic network analysis. We compare ChPepT1 to its human ortholog (hPepT1), a non-cold-adapted variant, to reveal key features enabling psychrophilic function. Our simulations show that ChPepT1 displays enhanced global flexibility, particularly in domains adjacent to the substrate-binding site and the C-terminal domain (CTD). While hPepT1 loses substrate binding affinity as temperature increases, ChPepT1 maintains stable peptide interactions across a broad thermal range. This thermodynamic buffering results from temperature-sensitive rearrangement of hydrogen bond networks and more dynamic lipid interactions. Importantly, we identify a temperature-responsive segment (TRS, residues 660–670) within the proximal CTD that undergoes an α-helix to coil transition, modulating long-range coupling with transmembrane helices. Dynamic cross-correlation analyses further suggest that ChPepT1, unlike hPepT1, reorganizes its interdomain communication in response to temperature shifts. Our findings suggest that cold tolerance in ChPepT1 arises from a combination of structural flexibility, resilient substrate binding, and temperature-sensitive interdomain dynamics. These results provide new mechanistic insight into thermal adaptation in membrane transporters and offer a framework for engineering proteins with enhanced functionality in extreme environments. Full article

Background/Objectives: Silicon dioxide nanoparticles (SiO₂NPs) do not exist in isolation in the environment but can interact with other substances, thus influencing their toxic effects on aquatic organisms. We assessed the combined impact of SiO₂NPs and N-acetylcysteine (NAC), an antioxidant with the potential to counteract nanoparticle-induced oxidative stress (OS). Methods: Behavioral assessments, including the social interaction test and color preference test, were performed to evaluate neurobehavioral changes. OS biomarkers, including malondialdehyde (MDA) levels for lipid peroxidation and the activity of key antioxidant enzymes such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were assessed to evaluate the extent of cellular damage. Results: The results indicate that prolonged exposure to SiO₂NPs induces significant behavioral disruptions, including reduced exploratory behavior and increased anxiety-like responses. Furthermore, biochemical analysis revealed increased OS, suggesting nanoparticle-induced cellular toxicity. NAC co-treatment partially reversed these effects, particularly improving locomotor outcomes and antioxidant response, but was less effective on social behavior. Conclusions: These findings highlight the ecological and health risks posed by SiO₂NPs and point toward the need for further toxicological studies on their long-term biological effects. Full article

Trachinotus ovatus is a euryhaline, warm-water pelagic fish species with strong adaptability, rapid growth, and a high survival rate, making it one of the most important marine aquaculture species in China. In recent years, extensive experience has been accumulated in the cage farming of T. ovatus, but whether it can adapt to deep-sea environments and grow normally remains a current research focus. This study used RNA-Seq sequencing technology to analyze the gene expression changes in the liver of T. ovatus under three conditions: rest (0 cm/s), medium flow velocity (54 cm/s), and high flow velocity (90 cm/s). Through differential expression analysis, Short Time-series Expression Miner (STEM) analysis and protein–protein interaction (PPI) network analysis, a total of 5107 differentially expressed genes (DEGs), three significantly expressed gene profiles (profile6, profile1, and profile5), and 15 hub genes were identified. The results showed that changes in flow speed significantly impacted key biological processes such as energy metabolism, protein homeostasis, and endoplasmic reticulum (ER) stress response. Under moderate and high flow conditions, glycolysis-related genes were upregulated to meet the energy demands of swimming, while the downregulation of the PPARγ-RXRG complex and its downstream genes in the lipid metabolism pathway suggested a limitation in its fatty acid β-oxidation capacity. At the same time, protein synthesis was enhanced, and the unfolded protein response (UPR) was activated to help cope with ER stress. Furthermore, when the flow speed reached 90 cm/s, the expression of UPR- related genes and the anti-apoptotic factor JNK significantly decreased, suggesting that the stress response was nearing its limit and could potentially trigger cell apoptosis. These findings provide new insights into the molecular adaptation mechanisms of T. ovatus to flow speed stress and offer theoretical support for its rational farming in deep-sea cages, suggesting that the water flow speed in farming should not exceed 90 cm/s. Full article

Agricultural organic pollutants have been identified as a key factor contributing to amphibian population decline, particularly during early developmental stages when tadpoles are frequently exposed to neonicotinoids (NEOs) and microplastics (MPs). In this study, Hoplobatrachus rugulosus tadpoles were exposed to imidacloprid (IMI: 0.045, 0.45, and 4.5 mg L⁻¹) and polyethylene-derived MPs (10 mg L⁻¹) from agricultural mulch films, both individually and in combination. We systematically evaluated acute toxicity, bioaccumulation, developmental and oxidative stress responses, and changes in the skin and gut microbiota. The results showed that the 96 h median lethal concentration (LC₅₀) of IMI was 44.8 mg L⁻¹ in the IMI-only group and was 40.5 mg L⁻¹ in the IMI + MPs group, indicating the negligible impact of MPs on acute toxicity. However, in the highest co-exposure group (IMI4.5 + MPs), tadpole body length and weight decreased by 14.7% and 22.6%, respectively, alongside marked changes in oxidative stress, whereby catalase (CAT) and superoxide dismutase (SOD) activities were suppressed, while malondialdehyde (MDA) levels increased by 35%, indicating elevated lipid peroxidation. Furthermore, the micronucleus frequency in erythrocytes was significantly elevated, suggesting genotoxic effects. Microbial community analysis revealed significant shifts in the relative abundance of gut and skin microbiota under IMI + MPs exposure, with a notable enrichment of Proteobacteria, Fusarium, Actinomycetota, and Bacteroidota, indicating the disruption of host–microbiome interactions. This study proposes a comprehensive multi-tiered assessment framework encompassing environmental exposure, bioaccumulation, toxicological endpoints, oxidative stress biomarkers, and microbiome shifts. Our findings provide new mechanistic insights and quantitative evidence on the compound threats posed by IMI and MPs to amphibians in aquatic environments. Full article

Life is defined descriptively by the capacity for metabolism, homeostasis, self-organization, growth, adaptation, information metabolism, and reproduction. All these are achieved by a set of self-organizing and self-sustaining processes, among which energy and information metabolism play a dominant role. The energy metabolism of the human body is based on glucose and lipid metabolism. All energy-dependent life processes are controlled by phosphate and calcium signaling. To maintain the optimal levels of energy metabolism, cells, tissues, and the nervous system communicate mutually, and as a result of this signaling, metabolism emerges with self-awareness, which allows for conscience social interactions, which are the most significant determinants of human life. Consequently, the brain representation of our body and the egocentric representation of the environment are built. The last determinant of life optimization is the limited life/death cycle, which exhibits the same pattern at cellular and social levels. This narrative review is my first attempt to systematize our knowledge of life phenomena. Due to the extreme magnitude of this challenge, in the current article, I tried to summarize the current knowledge about fundamental life processes, i.e., energy and information metabolism, and, thus, initiate a broader discussion about the life and future of our species. Full article

Thermosensitive hydrogel, as a smart polymer material, showed great potential for application in the field of wound repair due to its unique external temperature responsiveness and excellent biocompatibility. Chitosan, a natural macromolecular polysaccharide derived from the deacetylation of chitin, possessed not only strong interactions with biomolecules such as DNA, proteins, and lipids, but also unique biocompatibility and degradability. Chitosan-based thermosensitive hydrogels, prepared by compounding chitosan with surfactants, underwent sol–gel phase transitions at varying external temperatures, which provided an ideal healing environment for wounds. This comprehensive review was initiated by elucidating the sol–gel phase transformation mechanism underlying thermosensitive hydrogels and the intricate process of wound repair. In addition, this review provided a detailed overview of the prevalent types of chitosan-based thermosensitive hydrogels, highlighting their unique characteristics and applications in different types of wound repair. Finally, the challenges and development directions of chitosan-based thermosensitive hydrogels in wound repair were discussed, aiming to provide theoretical support and practical guidance for their future applications in wound healing. Full article

Extracellular vesicles (EVs) are nanometer-sized lipid structures actively secreted by Gram-negative and Gram-positive bacteria, representing a sophisticated microbial adaptation and communication strategy. These structures are involved in biomolecular transport, the regulation of biological processes, the modulation of host–pathogen interactions, and adaptation to hostile environmental conditions. EVs also play a crucial role in virulence, antibiotic resistance, and biofilm formation. This review will explore the biogenesis, composition, and biological mechanisms of outer membrane vesicles (OMVs) secreted by Gram-negative bacteria and membrane vesicles (MVs) generated by Gram-positive bacteria. In detail, the modulation of EVs in response to antibiotic exposure will be addressed. The role of EV morpho-functional adaptations will be studied in antimicrobial resistance, the gene determinant spread, and survival in adverse environments. This study aims to provide a comprehensive overview of the EV role in bacterial physiology, highlighting their ecological, evolutionary, and biotechnological implications. An overview of the enzymes and proteins mainly involved in OMV-mediated resistance mechanisms will also be provided. These insights could open new perspectives for developing therapeutic strategies that counteract EV secretion and biotechnological applications, such as vaccines and drug delivery systems. Full article

Antibiotic resistance has emerged as a critical global public health challenge, prompting increased interest in non-antibiotic antimicrobial strategies such as bacteriophage-derived endolysins. Although endolysins possess strong lytic potential, their application to Gram-negative bacteria remains limited due to the outer membrane barrier. PlyKp104 is a recently identified phage-derived endolysin that exhibits lytic activity against Gram-negative bacteria without the aid of membrane permeabilizers. In this study, the crystal structure of PlyKp104 was determined at a resolution of 1.85 Å. PlyKp104 consists solely of a catalytic SLT domain, and structure-based analysis revealed a putative active site and key structural features associated with substrate binding. Comparative analysis with homologous structures suggested that PlyKp104 belongs to lytic transglycosylase family 1. B-factor analysis and hydrophobic interaction mapping indicated that the domain exhibits high structural stability, supported by conserved hydrophobic residues clustered in motifs I and II. During structure determination, an unidentified electron density was consistently observed near a neutral, hydrophobic surface region. Its shape and environment suggest the presence of a lipid-like molecule, implying a potential lipid-binding site. These findings provide structural insight into PlyKp104 and contribute to the understanding of endolysin mechanisms against Gram-negative bacteria, with implications for future protein engineering efforts. Full article

Intertidal organisms experience daily environmental fluctuations, including changes in temperature, UV radiation, and aerial exposure during low tide, requiring physiological strategies for survival. One adaptation is the “preparation for oxidative stress” (POS), where antioxidants are upregulated preemptively to mitigate oxidative damage. While POS has been documented in over 120 species, in the case of intertidal species, most studies focus on single stressors under controlled-laboratory conditions. This study investigated POS in the sea urchin Echinometra lucunter under natural multi-stress conditions. Sampling occurred over a single day (from 5 a.m. to noon), analyzing three conditions: submerged (S), aerially exposed for 2 h (AE), and reimmersed for 2 h (R). There was a ~4 °C temperature increase in the AE group compared to the S group, with a peak of solar radiation during reoxygenation. Antioxidant enzyme activity—catalase, glutathione transferase (GST), and superoxide dismutase (SOD)—and lipid peroxidation (TBARS) were assessed in gonad and intestine tissues. GST activity increased by fourfold in the intestines of AE individuals, while TBARS was elevated in gonads, where no antioxidant upregulation happened. These results suggest that the POS-response (increase in GST) was triggered by the interaction of temperature and aerial exposure. This research emphasizes the critical importance of field studies in understanding complex, natural multi-stressor environments. Full article

Comparative studies using lysophosphatidic acid (LPA) and the synthetic agonist, oleoyl-methoxy glycerophosphothionate (OMPT), in cells expressing the LPA₃ receptor revealed differences in the action of these agents. The possibility that more than one recognition cavity might exist for these ligands in the LPA₃ receptor was considered. We performed agonist docking studies exploring the whole protein to obtain tridimensional details of the ligand–receptor interaction. Functional in cellulo experiments using mutants were also executed. Our work includes blind docking using the unrefined and refined proteins subjected to hot spot predictions. Distinct ligand protonation (charge −1 and −2) states were evaluated. One LPA recognition cavity is located near the lower surface of the receptor close to the cytoplasm (Lower Cavity). OMPT displayed an affinity for an additional identification cavity detected in the transmembrane and extracellular regions (Upper Cavity). Docking targeted to Trp102 favored binding of both ligands in the transmembrane domain near the extracellular areas (Upper Cavity), but the associating amino acids were not identical due to close sub-cavities. A receptor model was generated using AlphaFold3, which properly identified the transmembrane regions of the sequence and co-modeled the lipid environment accordingly. These two models independently generated (with and without the membrane) and adopted essentially the same conformation, validating the data obtained. A DeepSite analysis of the model predicted two main binding pockets, providing additional confidence in the predicted ligand-binding regions and support for the relevance of the docking-based interaction models. In addition, mutagenesis was performed of the amino acids of the two detected cavities. In the in cellulo studies, LPA action was much less affected by the distinct mutations than that of OMPT (which was almost abolished). Therefore, docking and functional data indicate the presence of distinct agonist binding cavities in the LPA₃ receptor. Full article

Background/Objectives: Seminolipid (sulfogalactosylglycerolipid (SGG)) is abundantly present on the sperm surface and its roles in sperm–egg interaction are well-documented. SGG liposomes have direct affinity for the zona pellucida (ZP), the egg extracellular matrix. SGG is also integral to the formation of sperm lipid rafts, which are platforms on the sperm surface for ZP binding. Our objective was to chemically synthesize a short-chain analog of SGG (SC-SGG with a C6 acyl chain instead of C16 in the natural lipid), which is solubilized in an aqueous environment, and to determine the inhibitory effects of SC-SGG in mouse sperm–egg interaction, and thus fertilization. Methods: SC-SGG was synthesized from a 3-O-galactopyranosyl-sn-glycerol intermediate protected on the sugar moiety through the acylation of glycerol with caproic acid, deprotection and regioselective 3-O-sulfation of the galactose residue. SC-SGG solubilized in a medium was used to treat sperm–egg co-incubates or to pretreat sperm or eggs before co-incubating sperm with eggs or vice versa. Sperm–ZP binding and fertilization (scoring eggs with two pronuclei) were microscopically assessed. Results: SC-SGG was efficiently synthesized with a 78% overall yield. SC-SGG inhibited sperm–ZP binding and fertilization of mouse gametes in a concentration-dependent manner, and at 6 µM SC-SGG, the mouse fertilization was zero. SC-SGG inhibited the fertilizing ability of both sperm and eggs, as shown in the pretreatment experiments. Conclusions: SC-SGG was an effective inhibitor of mouse fertilization in vitro. It warrants development to be a non-hormonal contraceptive. Full article

Significant regional variations in seawater characteristics (temperature, salinity, pH, nutrients) exist across marine environments, yet their impacts on abalone gastrointestinal microbiota and metabolites remain underexplored. This study investigated seawater nutrient and pH interactions on abalone gut ecosystems through comparative analysis of three marine regions (Pingtan (PT), Xiapu (XP), Lianjiang (LJ)). Seawater characteristics revealed distinct patterns: LJ exhibited the lowest total phosphorus (TP: 0.12 mg/L), total nitrogen (TN: 2.8 mg/L), NH₃-N (0.05 mg/L) but the highest salinity (32.1‰) and lowest pH (7.82), while PT/XP showed elevated nutrients (TP: 0.24–0.28 mg/L; TN: 4.2–4.5 mg/L). Microbial diversity peaked in LJ samples (Shannon index: 5.8) with dominant genera Psychrilyobacter (12.4%) and Bradyrhizobium (9.1%), contrasting with PT’s Mycoplasma-enriched communities (18.7%) and XP’s Vibrio-dominant profiles (14.3%). Metabolomic analysis identified 127 differential metabolites (VIP > 1.5, p < 0.05), predominantly lipids (38%) and organic acids (27%), with pathway enrichment in sulfur relay (q = 4.2 × 10⁻⁵) and tryptophan metabolism (q = 1.8 × 10⁻⁴). Stomach-specific metabolites correlated with fatty acid degradation (e.g., inosine diphosphate, r = −0.82 with vibrionimonas) and glutathione metabolism (methionine vs. mycoplasma, r = −0.79). Critically, pH showed negative correlations with beneficial Psychrilyobacter (oleamide: r = −0.68) and positive associations with pathogenic Vibrio (trigonelline: r = 0.72). Elevated NH₃-N (>0.15 mg/L) and TP (>0.25 mg/L) promoted Mycoplasma proliferation (R² = 0.89) alongside cytotoxic metabolite accumulation. These findings demonstrate that higher pH (>8.0) and nutrient overload disrupt microbial symbiosis, favoring pathogens over beneficial taxa. Full article

It has been reported that miR-375-3p plays a critical role in numerous diseases. To elucidate its biological function, particularly its differential expression and specific mechanisms of action in Alzheimer’s disease (AD) and small cell lung cancer (SCLC), this study comprehensively explores the associations between the target genes of miR-375-3p and both AD and SCLC. The focus is specifically on its impact on disease progression and the remodeling of the tumor microenvironment. We utilized databases such as the miRNA TargetScanHuman 8.0 database and the STRING database, to construct a protein–protein interaction (PPI) network for the classification and discrimination of the miR-375-3p gene, resulting in the identification of 14 intersecting target genes. Subsequently, two key genes, ASCL1 and CHD7, along with their associated genes, were further analyzed using Spearman correlation analysis. The identified key genes were then subjected to GO function annotation and KEGG pathway enrichment analysis. It was determined that pathways related to lipid metabolism, autophagy, and cell apoptosis were differentially expressed in the AD and SCLC environments, with nine related pathways identified, among which the PI3K pathway was the most prominent. Finally, we demonstrated that the expression of miR-375-3p significantly differed between the two environments, with higher expression levels observed in AD compared to SCLC. Our study confirmed that miR-375-3p can promote apoptosis, regulate lipid metabolism, influence the progression of neurodegenerative diseases, and inhibit the proliferation and metastasis of tumor cells. These research findings may have significant implications for the future treatment of AD and SCLC. Full article

Xiangxi Yellow Cattle, an indigenous Chinese livestock breed recognized for its exceptional nutrient composition and superior meat characteristics, has gained significant market preference among consumers. This investigation focused on evaluating physicochemical attributes, flavor development patterns, and bacterial population dynamics in chilled beef samples stored at 4 °C over an 8-day period. The research further examined interrelationships between meat parameters, predominant microbial species, and crucial aroma-active substances. Findings revealed a progressive elevation in lipid/protein oxidation levels, biogenic amine accumulation, and TVB-N values as microbial proliferation intensified toward the late storage phase. Microbial analysis demonstrated a final total viable count of 7.17 log10 (CFU/g), with bacterial community dominance distributed among Firmicutes (58.15%), Proteobacteria (29.56%), and Bacteroidota (12.05%). Notably, Brochothrix thermosphacta emerged as the primary spoilage organism in terminal storage phases. Volatile organic compounds (VOCs) in the beef during storage were analyzed, with a total of 66 compounds identified. The critical analysis identified 2,3-butanedione and 2-butanone as microbial metabolism-dependent substances showing strong correlations with meat quality parameters, emerging as freshness markers for beef evaluation. Importantly, the study highlighted the necessity for deeper investigation into microbial–VOC interactions, particularly considering the intricate bacterial ecosystems in aquatic environments. These outcomes enhance our understanding of spoilage mechanisms in Xiangxi Yellow Cattle beef while proposing practical approaches for microbial control in meat preservation systems. Full article