Search Results (809)

The MATα_HMGbox and HMG-box_ROX1-like domains of the MAT1-1-1 and MAT1-2-1 proteins, respectively, play essential roles in DNA binding and the subsequent regulation of gene transcription, controlling Ophiocordyceps sinensis sexual reproduction. Alternative splicing, differential occurrence and transcription of the MAT1-1-1 and MAT1-2-1 genes have been demonstrated in Hirsutella sinensis (GC-biased Genotype #1 of the 17 O. sinensis genotypes), suggesting self-sterility under heterothallic or hybrid outcrossing. In this study, the MATα_HMGbox domains of MAT1-1-1 proteins in wild-type Cordyceps sinensis isolates were shown to cluster into 5 clades in the Bayesian clustering tree and belong to diverse stereostructure morphs under 19 AlphaFold codes. The HMG-box_ROX1-like domains of MAT1-2-1 proteins, on the other hand, were shown to cluster into 2 branched Bayesian clades and belong to stereostructure morphs under 25 AlphaFold codes. Correlation analysis revealed that 1–3 amino acid substitutions in the DNA-binding domains of the mating proteins resulted in altered hydrophobicity and secondary and tertiary structures of the DNA-binding domains of the proteins, especially altered stereostructures of the hydrophobic cores formed by 3 critical α- helices within the functional domains of the proteins. Fungal origin analysis revealed possible heterospecific fungal sources of mating proteins with stereostructure variations in wild-type C. sinensis isolates, suggesting that alterations in DNA binding function and the subsequent regulation of mating-related gene transcription are involved in ensuring the accuracy and genetic diversity of heterothallic and hybrid reproduction of O. sinensis during the lifecycle of the C. sinensis insect–fungal complex. Full article

Bifidobacterium animalis subsp. lactis is a widely used probiotic, yet its efficacy is highly strain-specific, and growing antibiotic resistance necessitates rigorous safety evaluations. We used whole-genome sequencing and in vitro assays to characterize the safety and probiotic traits of infant feces-sourced strain BD1, which shows preliminary mood-modulating and anti-inflammatory potential. The BD1 genome showed a favorable safety profile. VFDB analysis identified 139 low-similarity homologs, with no major toxins detected. Only four chromosomally encoded antibiotic resistance genes were found; phenotypic testing confirmed resistance solely to tetracycline and mupirocin. Although the tetracycline resistance gene tet(W) was identified in genomic island GI01, the absence of associated mobile genetic elements results in a negligible risk of its mobilization. Functional annotation highlighted a dominant metabolic capacity for carbohydrate and amino acid metabolism. BD1 is rich in CAZymes, enabling superior utilization of diverse substrates (starch, sucrose, galactose). Enrichment in lipid metabolism pathways (glycerolipid, sphingolipid) further suggests potential for enhancing fermented product flavor. In vitro assessment demonstrated moderate gastrointestinal tolerance and strong bile salt tolerance. Surface properties showed pronounced cell surface hydrophobicity and confirmed biofilm-forming potential. In conclusion, BD1 exhibits robust safety, metabolic versatility, and strong probiotic characteristics, supporting its development as a functional probiotic strain. Full article

During gastrointestinal digestion, dietary proteins are hydrolyzed into peptides and free amino acids that modulate enteroendocrine function and satiety-related hormone secretion along the gut–brain axis, thereby contributing to obesity prevention. We investigated whey protein concentrate (WPC) as a source of bioactive peptides and evaluated the effects of its digests on cholecystokinin (CCK) secretion in STC-1 enteroendocrine cells by integrating the standardized INFOGEST in vitro digestion protocol, peptidomics (LC–MS/MS), and in silico bioactivity prediction. In STC-1 cells, the <3 kDa intestinal peptide fraction exhibited the strongest CCK stimulation, positioning these low-molecular-weight peptides as promising bioactive components for satiety modulation and metabolic health applications. Peptidomic analysis of this fraction identified short sequences derived primarily from β-lactoglobulin (β-La) and α-lactalbumin (α-La), enriched in hydrophobic and aromatic residues, including neuropeptide-like sequences containing the Glu–Asn–Ser–Ala–Glu–Pro–Glu (ENSAEPE) motif of β-La f(108–114). In silico bioactivity profiling with MultiPep predicted antihypertensive, angiotensin-converting enzyme (ACE)–inhibitory, antidiabetic, dipeptidyl peptidase-IV (DPP-IV)–inhibitory, antioxidant, antibacterial, and neuropeptide-like activities. Overall, digestion of WPC released low-molecular-weight peptides and amino acids that enhanced CCK secretion in vitro; these findings support their potential use in nutritional strategies to enhance satiety, modulate appetite and energy intake, and improving cardiometabolic health. Full article

A promising direction for the creation of new biologically active derivatives of the alkaloid lupinine is the synthesis of “hybrid molecules” that combine a fragment of the alkaloid and the pharmacophore of 1,2,3-triazole in their structure. From a biological perspective, this work presents the first X-ray diffraction study of a single crystal of (1S,9aR)-1-({4-[4-(Benzyloxy)-3-methoxyphenyl]-1H-1,2,3-triazol-1-yl}methyl)octahydro-2H-quinolizine, a new, recently synthesized 1,2,3-triazole derivative of lupinine. A comparison of theoretically predicted and experimentally observed structural parameters was carried out. The FTIR spectroscopy study and vibrational properties calculations allowed us to interpret the FTIR absorption spectrum and localize specific vibrational modes in quinolizidine, 1,2,3-triazole, and benzene rings. Such information can be fruitful for further characterization of the synthesis process and products. The molecular docking of the compound was performed. It was shown that the studied molecules are capable of interacting with the Mpro binding site via non-covalent and hydrophobic interactions with subsites S3 (Met165, Glu166, Leu167, Pro168) and S5 (Gln189, Thr190, Gln192), which ensure the stabilization of the Mpro substrate. Blocking of the active site of the enzyme in the region of the oxyanion hole does not occur, but stable stacking interactions with the π-system of one of the catalytic amino acids, His41, are observed. Full article

Compositional heterogeneity of oil bodies (OB) from nine high-oleic peanut (HOP) cultivars was systematically characterized. The results demonstrated that nine OB samples exhibited variability in R, G, and B values (red, green, and blue color channels), with the B channel values significantly differing among cultivars, while no significant color variation was observed in their overall appearance. Fats and proteins dominated the dry matter composition of OB, consistent with typical plant OB structural profiles. The high-fat OB of cultivars J572-O, J6-O, Z215-O, and H985-O exhibited outstanding efficiency in loading lipophilic bioactive compounds. OBs from J16-O, G37-O, Z215-O, J572-O, Y37-O, and Y65-O had a distinctive fatty acid profile: high-oleic acid and monounsaturated fatty acids (MUFAs), with reduced linoleic acid, palmitoleic acid, and saturated fatty acids (SFAs). All OB samples contained four tocopherol isomers (α-, β-, γ-, δ-), with α-tocopherol (5.07–12.59 mg/100 g) and γ-tocopherol (6.36–14.81 mg/100 g) as the predominant forms. Essential amino acids (EAAs) and hydrophobic amino acids were detected, with leucine, phenylalanine, and valine being highly abundant. TEAA/TAA and TEAA/TNEAA ratios complied with FAO/WHO standards. J16-O stood out with a balanced fatty acid profile, high tocopherols, and quality protein, making it a promising candidate for functional foods. Full article

Weissella viridescens has been proposed as a probiotic candidate, but strain-level multi-omics evidence remains limited. The complete genome of the human-derived W. viridescens strain Wv2365 was sequenced through a hybrid assembly of Illumina and PacBio sequencing reads and compared with eight publicly available W. viridescens genomes. Pangenome analysis and functional annotation were performed, and metabolites were profiled by broadly targeted metabolomic analysis. In addition, the acid and bile tolerance, auto-aggregation and cell surface hydrophobicity, and antioxidant activity of the strain, as well as both in silico and phenotypic safety, were assessed. Wv2365 carries a single chromosome of 1.57 Mb with 41.3% G+C content. The species has an open pangenome with 803 core genes. Genomic and metabolomic features converged on carbohydrate and amino acid metabolism, including glycolysis/tricarboxylic acid (TCA) cycle and arginine pathways, and a carbohydrate-active enzyme (CAZyme) repertoire dominated by glycosyltransferases. In vitro, Wv2365 tolerated pH 3.0 and 0.3% bile, showed auto-aggregation, surface hydrophobicity, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging. The strain was susceptible to 10 antibiotics tested except for its intrinsic vancomycin non-susceptibility and was non-hemolytic and gelatinase negative. No acquired antimicrobial resistance or virulence genes were found in the genome. These findings indicate that W. viridescens Wv2365 is safe with probiotic traits relevant to gastrointestinal survival, colonization, and redox balance. Full article

Oyster peptides (OPs) have gained increasing attention for their excellent biological activities, especially immunomodulatory effects. In this study, oyster proteins were fermented using Lactobacillus casei to prepare bioactive peptides, and the effects of fermentation parameters (time, temperature, and inoculum amount) on the degree of hydrolysis (DH) were optimized. The optimal fermentation conditions were determined as 30 h, 35 °C, and 5% inoculum amount, resulting in a DH of 28.24%. Structural characterization showed that OPs were mainly composed of low-molecular-weight peptides (<1000 Da) with high hydrophobic amino acid content, and they exhibited good stability during in vitro gastrointestinal digestion. In vitro immunological evaluation using RAW264.7 macrophages demonstrated that OPs significantly enhanced phagocytic activity and nitric oxide (NO) production, and upregulated the mRNA expression levels of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. Mechanistically, OPs exerted immunostimulatory effects by specifically activating the extracellular signal-regulated kinase (ERK) pathway within the mitogen-activated protein kinase (MAPK) signaling cascade, without significant alterations in the phosphorylation levels of p38 and c-Jun N-terminal kinase (JNK). These findings highlight the potential of Lactobacillus casei-fermented oyster peptides as natural immunomodulatory ingredients for functional food development. Full article

Sestrin2 (SESN2) is a highly conserved stress-inducible protein that serves as a central hub for integrating cellular responses to nutrient availability, oxidative stress, and endoplasmic reticulum (ER) stress. A key function of SESN2 is its role as a direct sensor for the branched-chain amino acid (BCAA) leucine, which modulates the activity of the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cell growth and metabolism. While the functional link between leucine and SESN2 is well-established, the precise molecular determinants that confer its high specificity for leucine over other BCAAs, such as isoleucine and valine, remain poorly understood. This study employs an integrated computational approach, spanning atomic interactions to global protein dynamics, combining molecular docking, extensive all-atom molecular dynamics (MD) simulations, and binding free energy calculations, to elucidate the structural and dynamic basis of BCAA-SESN2 recognition. Our thermodynamic analysis reveals a distinct binding affinity hierarchy (Leucine > Isoleucine > Valine), which is primarily driven by superior van der Waals interactions and the shape complementarity of leucine’s isobutyl side chain within the protein’s hydrophobic pocket. Critically, a quantitative analysis of the conformational ensemble reveals that leucine induces a dramatic collapse of the protein’s structural heterogeneity. This “conformational locking” mechanism funnels the flexible, high-entropy unbound protein—which samples 35 distinct conformations—into a sharply restricted ensemble of just 9 stable states. This four-fold reduction in conformational freedom is accompanied by a kinetic trapping effect, which significantly lowers the rate of transitions between states. This process of conformational selection stabilizes a well-defined, signaling-competent structure, providing a comprehensive, atom-to-global-scale model of SESN2’s function. In the context of these findings, this work provides a critical framework for understanding SESN2’s complex role in disease and offers a clear rationale for the design of next-generation allosteric therapeutics. Full article

Resveratrol (RES) suffers from low bioavailability and poor gastrointestinal stability, limiting its health benefits. To overcome these challenges, we developed biomimetic mineralized nanoparticles based on walnut protein peptides (WPP-RES@CaP) for intestinal-targeted RES delivery. WPP with a 31.83% degree of hydrolysis was optimal for RES encapsulation. Subsequent mineralization with 5 mM Ca²⁺ significantly enhanced the encapsulation efficiency (EE) to 95.86%, compared to 73.69% for non-mineralized WPP-RES nanoparticles. The particle size and zeta potential of WPP-RES@CaP were 795 ± 16 nm and −27 ± 1 mV, respectively. Beyond the initial hydrophobic and π-π interactions, mineralization introduced additional stabilizing forces, including metal–ligand coordination, salt bridges, and electrostatic interactions, which collectively enhanced the structural integrity and RES retention of WPP-RES@CaP. During in vitro gastrointestinal digestion, the formation of a CaP shell protected RES and WPP from excessive degradation in the gastric phase. The 77.57% RES in WPP-RES@CaP was continuously released in the intestinal phase, which was higher than that of WPP-RES (49.73%). Meanwhile, the introduction of Ca²⁺ promoted the antioxidant activity of WPP-RES@CaP, which demonstrated higher DPPH and ABTS radical-scavenging activity assays than WPP-RES both before and after digestion. It was probably due to the synergistic effect of more released RES, antioxidant-free amino acids, and peptides. This mineralized peptide-based system provided a strategy for improving the delivery of hydrophobic bioactive compounds in functional foods. Full article

Sweat, which contains a rich array of biomarkers, serves as a vital biological fluid for non-invasive biosensing. Wearable sweat sensors have garnered significant interest owing to their portability and capacity for continuous monitoring. However, there are safety concerns regarding the direct contact of sweat sensors with the skin during the detection process. The chemical substances in the sensor patches may cause contamination of the epidermis when in contact with the skin, leading to skin allergic reactions. Sample collection and biosafety isolation are critical issues in wearable sweat detection. To address this, we develop a cactus-inspired biomimetic Janus membrane capable of unidirectionally transporting and concentrating sweat toward a designated detection zone. Through unidirectional transport from the hydrophobic layer to the hydrophilic layer of the Janus membrane, sweat droplets are enriched at the designated detection point of the conical hydrophilic pattern via Laplace pressure. The bionic osmosis-enrichment sensing patch effectively inhibits direct contact between indicators and skin, eliminating potential epidermal contamination. This achieved the effect of in situ perspiration collection under the premise of biosafety isolation. To rapidly and accurately analyze sweat biomarkers, we employ a deep learning (DL)-assisted fluorescence sensor for efficient and precise detection of biomarker concentrations. A dataset of 4500 fluorescence images are constructed and used to evaluate two DL and seven machine learning (ML) algorithms. The convolutional neural network (CNN) model could easily and accurately classify and quantitatively analyze the total concentration of the amino acid mixture, Ca²⁺ and Cl⁻, with 100% classification accuracy. The consistency between the detection results of actual sweat by the DL-assisted fluorescence method and fluorescence spectroscopy was 91.4–96.0%. This approach demonstrates high reliability in sweat collection and analysis, offering a practical tool for clinical health monitoring, early disease intervention, and diagnosis. Full article

Biochar is one of the most promising crop straw utilization pathways. However, its capacity for adsorbing heavy metals is limited, and there is a potential risk of secondary pollution, highlighting the importance of developing efficient and environmentally friendly bio-modification methods. Here, we utilized glomalin-related soil protein (GRSP), a byproduct from arbuscular mycorrhizal fungi, to modify straw biochar, developing a novel composite material and systematically evaluating its performance in removing copper ion (Cu²⁺) from aqueous solutions. Biochar samples derived from maize, wheat, and rice straw were prepared at three pyrolysis temperatures (300 °C, 500 °C, and 700 °C), followed by surface functionalization with GRSP to produce GRSP-modified straw biochar for Cu²⁺ adsorption experiments. The results demonstrated that the abundant functional groups (e.g., amino and carboxyl groups) in GRSP and the porous structure of the straw biochar exhibited a significant synergistic effect, enhancing the adsorption capacity for Cu²⁺. Notably, the GRSP-modified wheat straw biochar prepared at 700 °C achieved an adsorption capacity of 193.2 mg g⁻¹ for Cu²⁺, representing a 76% improvement over the unmodified material. Fourier transform infrared spectroscopy and scanning electron microscopy with energy-dispersive X-ray spectroscopy revealed that hydroxyl, carboxyl, and ether groups served as key adsorption sites for Cu²⁺, while the hydrophobic-acid precipitation characteristics of GRSP further enhanced the material’s recoverability. By systematically characterizing the material’s microstructure and its adsorption behavior toward Cu²⁺, this study elucidated the role of critical functional groups in the adsorption mechanism. This work not only offers a low-carbon and efficient strategy for agricultural waste valorization and heavy metal pollution control, but also advances the mechanistic understanding of “bio-abiotic” synergy in environmental remediation. Full article

Peptaibols represent a large family of membrane-active, linear fungal peptides, with variable lengths from 5 to 21 α–amino acid residues. As products of nonribosomal peptide synthetase (NRPS) biosynthetic machinery, they encompass several non-proteinogenic amino acids, particularly the Cα–tetrasubstituted residues, such as α–aminoisobutyric acid (Aib) and its homologue isovaline (Iva). Further distinctive features include an N-acyl terminus, such as an acetyl group, and a C-terminus containing an amino alcohol residue (such as phenylalaninol, leucinol, and valinol, among others), which neutralize charges at both termini and confer them a hydrophobic nature. Peptaibols not only represent the most abundant class among nonribosomal peptides, but they have also attracted continuous scientific interest due to their diverse pharmacological properties, including antimicrobial, cytotoxic, antifungal, and antiviral activities. In this review, we present for the first time the recently explored chemodiversity of fungal peptaibiotics derived from marine sources, with a particular focus on peptaibols. We discuss their distinctive structural features, chemical characterization, biosynthetic pathways, and biological activity profiles, with the aim of supporting ongoing research toward their development as potential pharmaceutical agents. Full article

Renin, a key aspartic protease central to the renin–angiotensin–aldosterone system (RAAS), remains a therapeutic target for hypertension despite the withdrawal of the only approved direct renin inhibitor, Aliskiren, due to unfavorable drug–drug interactions and safety concerns. Here, we report a computational protein design-driven evaluation of (S)-3-((3-(1H-imidazol-1-yl)propyl)amino)-2-(((S)-1-carboxy-2-(cyclooctanecarboxamido)ethyl)amino)-3-oxopropanoic acid (N-CDAH), a novel lipophilic cyclooctanoyl- derivative, as a next-generation renin inhibitor scaffold. This scaffold was designed based on the rationale of leveraging the carnosine like backbone while optimizing lipophilicity and metabolic stability. Pharmacokinetic, ADME, and toxicity predictions (SwissADME, pkCSM) revealed greater predicted aqueous solubility, enhanced metabolic stability, and significantly reduced off-target liabilities compared with Aliskiren (specifically, non-inhibition of major CYP isoforms). Molecular docking (AutoDock Vina binding affinity: −8.08 kcal/mol; Maestro Induced Fit Docking score: −11.149 kcal/mol) and molecular dynamics simulations confirmed favorable binding interactions, conformational adaptability, and complex stability within the renin active site. To contextualize its performance within the broader chemical space, the diastereomeric analog of N-CDAH as well as structurally related compounds identified through SwissSimilarity were also examined using computational workflow. The MD analysis (200 ns) demonstrated that the inhibitor is anchored via a dual stabilization mechanism: hydrophobic enclosure coupled with persistent ionic interactions. These integrative in silico results highlight the potential of this derivative to overcome Aliskiren’s pharmacological shortcomings, providing a strong computational rationale for experimental validation and underscoring the role of structure-based drug design in antihypertensive drug discovery. Full article

This study systematically investigates the effects of enzyme type (Alcalase, Trypsin, Protamex) on the properties of rice peptide nanoparticles (RPNs) and their efficacy in stabilizing high internal phase emulsions (HIPEs). RPNs prepared with Alcalase (RPNs-alc) exhibited the smallest particle size (≈379.6 nm), a uniform unimodal distribution, the highest content of hydrophobic amino acid, and the strongest DPPH (2,2-Diphenyl-1-picrylhydrazyl) radical scavenging activity (57.32%). In contrast, RPNs from Protamex (RPNs-pro) showed larger, heterogeneous particles with a bimodal distribution and lower antioxidant capacity. Interfacial characterization revealed that RPNs-alc had a superior three-phase contact angle, indicating enhanced interfacial activity. Structural stability analysis confirmed that hydrophobic interactions and hydrogen bonds are the primary forces maintaining all RPNs. Consequently, HIPEs stabilized by RPNs-alc and RPNs-typ displayed solid-like behavior and a regular network microstructure, leading to exceptional physical stability. Conversely, RPNs-pro led to unstable HIPEs with non-uniform droplets and interfacial aggregation, promoting droplet flocculation. These findings demonstrate that enzyme selection critically determines the functional properties of RPNs, with Alcalase-derived RPNs being the most effective bifunctional particles, offering a viable pathway for valorizing proteolytic by-products in fabricating stable, antioxidant-rich Pickering emulsions. Full article

Background: Accurately predicting protein druggability is crucial for successful drug development, as it significantly reduces the time and resources required to identify viable drug targets. However, existing methods often face trade-offs between accuracy, efficiency, and interpretability. This study aims to introduce a lightweight framework designed to address these challenges effectively. Methods: We present a lightweight framework that embeds proteins into four biologically informed, non-Euclidean metric spaces, derived from analyses of amino acid sequences, predicted secondary structures, and curated post-translational modification (PTM) annotations. These representations capture key features such as hydrophobicity profiles, PTM densities, spatial patterns, and secondary structure composition, providing interpretable proxies for structure-related determinants of druggability. This approach enhances our understanding of protein functionality while improving druggability predictability in a biologically relevant context. Results: Evaluated on an Aspirin-binding protein dataset using leave-one-out cross-validation (LOOCV), our distance-based ensemble achieves 92.25% accuracy (AUC = 0.9358) in the whole-protein setting. This performance significantly outperforms common sequence-only baselines in the literature while remaining computationally efficient. Conclusions: On a refined single-chain subset, our framework demonstrates performance comparable to established feature engineering pipelines, highlighting its potential effectiveness in practical applications. Together, these results strongly suggest that biologically grounded, non-Euclidean embeddings provide an effective and interpretable alternative to resource-intensive 3D pipelines for target assessment in drug discovery. This approach not only enhances our ability to assess protein druggability but also streamlines the overall process of target identification and validation. Full article