Biomolecules最新文献

Swida wilsoniana is an important oil-producing tree species whose fruits are rich in unsaturated fatty acids with high nutritional and medicinal value. Lipases are involved not only in lipid mobilization but also potentially in the regulation of fatty acid composition and oil accumulation in plants. In this study, the fatty acid composition of S. wilsoniana fruits was analyzed using gas chromatography-flame ionization detection (GC-FID), and the three most abundant fatty acids were selected as molecular docking ligands. Based on overall multi-ligand docking performance (including mean affinity across the three ligands), three key lipases-SwL5, SwL8, and SwL12-were identified as having the strongest interactions with these fatty acids. Phylogenetic analysis revealed that SwL5 and SwL12 belong to lipase family II, while SwL8 is classified into family VI. Molecular dynamics simulations were further performed to evaluate the binding stability and to characterize the structural basis of substrate recognition, including key interacting residues. This study provides theoretical insights into the molecular regulation of fatty acid composition in S. wilsoniana, and offers potential gene targets for the genetic improvement of oil quality traits.

Cell fate determination depends on precise and timely control of gene expression programs governed by enhancers, which act as central regulatory elements within chromatin landscapes. Recent studies reveal that enhancers occupy distinct functional states, including poised, primed, and active configurations, and that these states dynamically transition during lineage specification. These transitions, in turn, coordinate chromatin accessibility and transcriptional competence, establishing when and how developmental genes become activated. Beyond individual enhancers, some fate-defining loci employ modular and shadow enhancer architectures that cooperatively regulate transcriptional dose, maintain threshold stability, and buffer developmental programs against stochastic and environmental variation. Comparative analyses across neural, cardiac, and hematopoietic systems illustrate how these enhancer modules are selectively deployed to achieve lineage-specific precision and robustness. Furthermore, enhancer timing, persistence, and quantitative thresholds collectively encode developmental tempo and stability, ensuring faithful progression of cell fate transitions. By considering molecular state transitions together with cooperative enhancer architecture, this review organizes current views on how enhancers may help translate transient cues into stable lineage outcomes, thereby linking chromatin dynamics to developmental precision.

In this study, the synergistic effects of dietary Bacillus velezensis AAHM-BV2301, silica nanoparticles (SiNPs), and chitosan (CS) on the growth performance, innate immunity, gut microbiota, and disease resistance of Asian seabass (Lates calcarifer) fingerlings were evaluated. A total of 400 fish (11.25 ± 2.12 g) were assigned to five dietary treatments for 30 days: control, BV (1 × 10⁸ CFU/kg feed), BVSiNP (1 × 10⁸ CFU/kg + 2 mg SiNP/kg), BVCS (1 × 10⁸ CFU/kg + 15 g CS/kg), and BVSiNPCS (combined additives at the same concentrations). The growth indices (WG, SGR, RGR, and FCR) significantly increased in the fish fed BVSiNPs, whereas the level of innate immunity increased across all the supplemented groups, with BVCS and BVSiNPCS having the strongest respiratory burst and lysozyme activities. The tissue-specific modulation of immune-related genes (α2M, HSP70, Mx, and C3) was most pronounced in BVSiNP-fed fish, particularly in the gills and liver. Gut microbiome profiling revealed enrichment of Cetobacterium somerae in response to BV-based treatments, whereas BVSiNPCS induced the greatest increase in microbial richness and network connectivity. Postchallenge survival against Vibrio vulnificus was significantly greater in the BV and BVSiNP groups (p < 0.05). Overall, SiNPs acted as functional enhancers of the B. velezensis probiotic, supporting improved growth, immune activation, and microbiota restructuring. These results highlight the potential of nanoparticle-integrated synbiotics for microbiome-targeted health management in aquaculture.

Spinal cord injury (SCI) is a debilitating condition resulting in a range of neurological impairments up to complete loss of function below the level of injury. With current clinical management limited to decompression and stabilisation of the injury, there is urgent need to develop effective restorative treatments. In animal models, cell transplantation therapies are being tested that utilise different cell types including olfactory ensheathing cells (OECs), a type of glial cell, to support and promote regeneration. While OECs have a unique combination of properties highly suitable for SCI repair, their efficacy and consistency need to be improved. Evidence suggests a combinational approach using growth factors or compounds alongside OECs may stimulate their innate properties and alter the internal milieu of an injury site in favour of neural repair. Naturally, there is intricate interplay between various growth factors and OECs during development of the olfactory system, and in injury and repair events, which regulate their migration, phagocytosis, and proliferation. Therefore, exploiting different growth factors to selectively enhance OECs' therapeutic potential could lead to restorative treatment of SCI. While some studies have already explored using growth factors to treat SCI in animal models, an optimal 'cocktail' has yet to be identified. In seeking to identify such a cocktail, this review presents the current understanding of SCI and the therapeutic potential of OECs and explores combined use of growth factors and OECs to improve treatment outcomes.

Background: Amyloid-related imaging abnormalities (ARIA) have gained significance in the context of anti-amyloid therapies (AATs), exhibiting clinical and radiological manifestations that overlap with Cerebral Amyloid Angiopathy-related inflammation (CAA-ri). This review aims to elucidate the similarities and differences between spontaneous (sARIA) and drug-induced ARIA (dARIA).

Methods: We conducted a narrative review comparing sARIA and dARIA, focusing on their underlying mechanisms, clinical presentations, and implications for diagnosis and treatment.

Results: Both sARIA and dARIA are characterized by similar pathophysiological mechanisms involving amyloid deposits and neuroinflammation. Notably, ARIA can manifest as ARIA-E (edema) or ARIA-H (hemorrhage), with varying incidence rates in clinical trials. The review highlights that while sARIA occurs independently from treatment, dARIA is associated with AAT and can lead to significant symptomatic presentations.

Conclusions: Understanding the continuum between sARIA and dARIA is crucial for improving diagnostic criteria, risk stratification, and therapeutic approaches. The proposed unified framework emphasizes the need for consensus in managing these conditions and advancing future research in amyloid-related diseases.

Mesothelial cells line serosal cavities and internal organs, playing a vital role in maintaining serosal integrity and homeostasis. Their remarkable plasticity and ability to undergo mesothelial-to-mesenchymal transition (MMT) position them as key regulators of tissue repair. However, when normal repair processes fail, mesothelial cells can acquire a profibrotic phenotype. They actively contribute to all stages of fibrosis development, including inflammation, fibrin accumulation, myofibroblast differentiation, and extracellular matrix (ECM) remodeling. Fibrotic progression involves multiple cell types, and communication among them is essential for its perpetuation. Mesothelial cells are implicated in bidirectional crosstalk with fibroblasts, macrophages, lymphocytes, and endothelial cells of the serosal microenvironment through direct contact, paracrine signaling, and extracellular vesicle exchange. These interactions regulate immune cell recruitment, cytokine balance, endothelial permeability, and ECM deposition, while, in turn, immune and endothelial cells modulate mesothelial activation, proliferation, and transition. Understanding this complex network of intercellular communication provides new insights into fibrosis pathogenesis and reveals promising targets for antifibrotic therapies.

The intestine is considered a habitat for both bacteria and parasites. In this study, many fecal bacterial isolates and the protozoan Blastocystis sp. were recovered from stool samples of individuals with gastrointestinal conditions. Isolated bacteria were tested for extracellular protease production, and the most potent producer was identified by 16SrDNA gene sequencing as P. aeruginosa FZM498. The enzyme was extracted and purified to electrophoretic homogeneity by the DEAE-Sepharose ion-exchanger and SDS-PAGE revealed a major band at 42.15 KDa. It exhibited maximal activity at 35 °C with thermostability at 60 °C (T_1/2 = 200.04 min). It was most active at pH 8.0 and stable at 5.0-9.5. Enzymatic activity was greatly stimulated in the presence of Fe²⁺ ions, but was repressed by Zn²⁺ and Hg²⁺ ions. Inhibition by PMSF, TLCK, aprotinin, benzamidine, and SBTI protease reagents suggests a serine protease family. The V_max and K_m dynamic constants against azocasein were 36.232 U/mL and 0.0072 mM, respectively. It exhibited the lowest K_m value against the synthetic substrate D-Val-Leu-Lys-pNA among all substrates, indicating a plasmin-like activity. Interestingly, when tested against Blastocystis sp., cysts appeared progressively shrunken, ruptured, and mycelial-like, indicating complete structural collapse with leakage of intracellular contents. The importance of this research is that it is the first study to test the anti-Blastocystis activity of an extracted bacterial serine protease from the gut. This could be a promising, eco-friendly, natural alternative as an anti-Blastocystis agent. The objective of this study was to isolate, purify, and biochemically characterize an extracellular serine protease produced by gut-associated bacteria, as well as to assess its in vitro anti-Blastocystis efficacy as a potential natural and ecologically friendly antiparasitic therapy.

Microtubules are hollow cylindrical polymers made up of tubulin. This heterodimeric protein, tubulin, exists in multiple forms: tubulin isotypes and tubulin isoforms. Distinct α- and β-tubulin genes give rise to tubulin isotypes, which differ in their amino acid sequences and cellular expression patterns. The tubulin post-translational modifications (PTMs) encode regulatory information within the microtubule lattice, modifying its biophysical characteristics and shaping interactions with motor proteins and microtubule-associated proteins. Different tubulin isotype compositions and post-translational modification patterns generate distinct tubulin isoforms. These isoforms are tissue-specific and regulate the functions of microtubules in specialized cells and cellular components such as cilia. Tubulin isoforms control cellular transport, regulate mechanosensitivity and shape the cytoskeleton, impacting the cellular functions and homeostasis. This review discusses the tubulin PTMs, including acetylation, methylation, palmitoylation, polyamination, glutamylation, glycylation, tyrosination, phosphorylation, SUMOylation, and ubiquitination, with emphasis on how isotype diversity and PTM-driven regulation together modulate microtubule behaviour, intracellular transport, and cellular functions.

Flow velocity is a key environmental factor that exerts multifaceted effects on fish growth and adaptation. Through long-term natural selection, fish have evolved adaptability to specific flow conditions, which not only relate to oxygen supply and food acquisition but also play a decisive role in reproduction, development, and population maintenance. To investigate the genomic mechanisms through which hydrodynamic environments drive divergence in closely related species, we focused on two sister species, Hemiculter bleekeri and Hemiculter leucisculus, which are adapted to contrasting flow regimes. We generated high-quality, chromosome level telomere-to-telomere (T2T) genomes and integrated comparative genomic analyses, we investigated the genetic basis underlying body shape regulation and reproductive strategies, aiming to decipher the adaptive evolutionary patterns of these species in response to differing hydrodynamic conditions from an integrated genotype phenotype perspective. We integrated PacBio HiFi, Hi-C, and Oxford Nanopore Technologies (ONT) ultra-long read sequencing data to construct high-quality T2T reference genomes for both species. The final genome assemblies are 0.998 Gb for H. bleekeri and 1.05 Gb for H. leucisculus, with each species possessing 24 chromosomes and all chromosomal sequences assembled into single contigs. Contig N50 values reached 40.45 Mb and 40.66 Mb, respectively, and both assemblies are gap-free. BUSCO assessments yielded completeness scores of 99.34% for both genomes, confirming their high continuity and accuracy. Integrated morphometric and genomic analyses revealed distinct adaptive strategies in two Hemiculter Species. H. bleekeri has evolved a streamlined body, underpinned by expansions in body shape related genes, and a pelagic egg strategy. In contrast, the adhesive egg strategy of H. leucisculus is supported by expansions in adhesion-related gene families. This divergence reflects adaptation to distinct flow velocity. By combining high-quality chromosome-level T2T genomes with morphometric and comparative genomic approaches, this study establishes a comprehensive framework for understanding the molecular mechanisms underlying adaptive evolution in freshwater fishes inhabiting contrasting flow velocity.

Thrombospondin-1 (TSP1) is a multifunctional glycoprotein that plays a crucial role in angiogenesis and vascular remodeling. Ser93 of TSP1 has recently been identified as a novel phosphorylation site, influencing angiogenic properties; however, the underlying signaling mechanism remains unclear. Here, we investigated the functional impact of Ser93 phosphorylation using phosphomimetic (TSP1^S93D) and phosphonull (TSP1^S93A) mutants. Endothelial cell (EC) migration was analyzed using scratch assay and electric cell-substrate impedance sensing. Activation of key pathways (Akt, p38, ERK, and FAK) was analyzed by immunoblotting. TSP1 secretion was quantified by ELISA. Downstream effects on smooth muscle cells were examined by Western blot using conditioned media of endothelial cells. Expression of TSP1^S93D significantly impaired endothelial migration and wound closure, associated with reduced phosphorylation of FAK and paxillin. Upstream of FAK signaling, TSP1^S93D showed enhanced binding to integrin β1 and promoted its clustering. In contrast, TSP1^S93D stimulated smooth muscle cell proliferation, migration, cytoskeletal remodeling, and phenotypic switching toward a synthetic, pro-inflammatory state characterized by elevated marker protein expression. Together, these findings demonstrate that the impaired angiogenic properties induced by TSP1^S93D result from the modulation of integrin β1-FAK pathways in ECs, suppressing endothelial motility while promoting smooth muscle activation, suggesting a role in early vascular remodeling and inflammation.