Search Results (3,095)

Background: Biotinidase deficiency (BD) is a common autosomal recessive metabolic disorder in Qatar and the Arab world. It is treatable if detected early, making it essential to understand the genetic variants involved. This study aimed to investigate the carrier frequency of BD-related variants in a healthy Qatari population, reflecting the genetic landscape of the broader Middle Eastern region; classify them using bioinformatics tools; and compare findings with global datasets. Methods: Whole-genome sequencing data from 14,669 participants in the Qatar Genome Program (QGP), a multiethnic cohort including Qatari nationals and long-term residents (≥15 years), were analyzed to identify BTD variants. A total of 723, including 653 single-nucleotide polymorphisms (SNPs) and 70 structural variants (SVs) in BTD associated with BD, were screened against the Qatari cohort and compared with international data. In silico tools were used to assess variant pathogenicity, conservation, and protein stability. Molecular dynamics (MD) simulations were performed to evaluate structural and functional changes in the BTD. Results: A total of 80 SNPs and 3 SVs were identified, among which 21 variants (19 SNPs and 2 SVs) were classified as pathogenic or likely pathogenic, according to ClinVar. The carrier frequency of BTD-related variants in Qatar was 1:20, primarily driven by rs13078881 (D444H). Molecular dynamics (MD) simulations revealed significant conformational changes with H323R, D444H, and P497S, which demonstrated increased flexibility (higher RMSD/RMSF and PCA trace values). Additionally, R209C and D444H showed reduced compactness (higher Rg) and distinct energy minima, suggesting altered conformational states. Conclusions: This study demonstrates a high carrier frequency of pathogenic BTD variants in the Qatari population, underscoring the need to integrate these SNPs and SVs into the national genomic neonatal screening program (gNBS) for enhanced early detection and treatment strategies. The mild structural deviations observed in the D444H mutant through MD simulations may explain its association with milder clinical phenotypes of BTD, offering valuable insights for personalized therapeutic approaches. Full article

Sophorolipids (SLs) constitute a group of unique biosurfactants in light of their unique properties, among which their physicochemical characteristics and antimicrobial activity stand out. SLs can exist mainly in acidic and lactonic forms, both of which display inhibitory activity. This study explores the interaction of non-acetylated acidic SL with bovine serum albumin (BSA). SL significantly enhances BSA’s thermal stability, increasing its midpoint unfolding temperature from 61.9 °C to approximately 76.0 °C and ΔH from 727 to 1054 kJ mol⁻¹ at high concentrations, indicating cooperative binding. Fourier-Transform Infrared Spectroscopy (FTIR) analysis confirms SL’s protective effect against thermal unfolding, enabling BSA to maintain its helical structure at 70 °C, distinguishing it from other surfactants that cause denaturation. Furthermore, SL fundamentally alters the sequence of thermal unfolding events; β-aggregation precedes helical domain unfolding, suggesting protective binding to BSA’s helical regions. Computational docking reveals high-affinity binding (Kd = 14.5 μM). Uniquely, SL binds between BSA domains IB and IIIA, establishing hydrophobic interactions, salt bridges, and hydrogen bonds, thus stabilizing the protein’s 3D structure. This distinct binding site is attributed to SL’s amphipathic character. This work deepens the understanding of the molecular characteristics of SL–protein interactions and contributes to improving the general knowledge of this outstanding biosurfactant. Full article

Functional ingredients such as dietary fibers, probiotics and prebiotics, polyphenols, omega-3 fatty acids, and bioactive peptides are increasingly central to food systems that aim to deliver health benefits beyond basic nutrition. This review explores how molecular structure, physicochemical properties, metabolism, and microbiome interactions affect bioactivity and bioavailability. We highlight advances in green extraction, encapsulation technologies, and 3D/4D printing that enhance the stability and targeted delivery of bioactives. AI-enabled tools for ingredient discovery, structure–activity modeling, and personalized formulation are also discussed. Sensory research and market insights inform strategies to improve consumer acceptance, while clinical studies provide evidence for cardiometabolic, immune, and cognitive benefits. Safety and regulatory aspects are addressed, particularly for emerging proteins and delivery systems. By integrating scientific and technological developments across disciplines, this review provides a comprehensive foundation for future research and commercialization of safe, effective, and personalized functional food products. Full article

The hepatitis D virus (HDV) is a small, defective RNA virus that induces the most severe form of viral hepatitis. Despite its severity, HDV infections are under-diagnosed due to non-standardized and costly diagnostic screening methods. However, limited research has been conducted on characterizing HDV-specific antibodies as alternative tools for diagnosis. Thus, we generated HDV-specific, polyclonal antibodies by immunizing rabbits with the HDV protein, small hepatitis delta antigen (SHDAg), in its oligomeric or denatured form. We identified SHDAg-specific linear epitopes by peptide array analysis and compared them to epitopes identified in HDV-infected patients. Using in silico structural analysis, we show that certain highly immunogenic domains in SHDAg, such as the coiled-coil domain, are masked in the oligomeric conformation of the protein; others, such as the second arginine-rich motif, are exposed. The nuclear localization signal is presumably exposed only by specific interaction of oligomeric HDAg with the HDV-RNA genome. Through surface plasmon resonance analysis, we identified two polyclonal antibodies derived from rabbit antisera with affinities in the lower nanomolar range. These antibodies were used to establish an ELISA that can quantitatively detect HDV virions in vitro and upon further optimization could be used as a promising alternative diagnostic screening method. Full article

P23-77 is a thermophilic bacteriophage that infects Thermus thermophilus bacteria. The genome of the virus is enclosed in an icosahedral capsid. This capsid is made of the small major capsid protein (VP16), the large major capsid protein (VP17), and the minor capsid protein (VP11). In addition to these three structural proteins, membrane-associated proteins (VP15, VP19, VP20, VP22, and VP23) have been identified in the virus and may serve as scaffold proteins to help with viral assembly. Previous studies have expressed VP11, VP16, and VP17 in E. coli. A mixture of these proteins can lead to the formation of complexes. However, the potential to express membrane-associated proteins has never been explored. Here, we demonstrated, for the first time, the expression and co-expression of some membrane-associated proteins with capsid (coat) proteins, both in the natural host and in E. coli. Co-expression of these proteins did not result in the assembly of virus-like particles. We explored further strategies to express and purify some of the proteins for future studies. We observed that the insertion of a purification tag (Strep-II tag, but not a histidine tag) significantly reduced the expression levels of some of the proteins. Six of the eight structural proteins were successfully purified to homogeneity using different approaches. We showed that VP20 and VP22 migrated on SDS PAGE gel at sizes larger than their predicted molecular weights. Predicted 3D structures of the proteins show that most of them are helical in nature with disordered regions. The work presented here will help pave the way for the expression and purification of these proteins. This will help determine their 3D structures and may shed light on the requirements for viral assembly. Full article

Reliable prediction of chemical–protein interactions (CPIs) remains a key challenge in drug discovery, especially under sparse or noisy biological data. We present MM-TCoCPIn, a Multi-Modal Topology-aware Chemical–Protein Interaction Network that integrates three causally grounded modalities—network topology, biomedical semantics, and a 3D protein structure—into an interpretable graph learning framework. The model processes topological features via a CTC (Comprehensive Topological Characteristics)-based encoder, literature-derived semantics via SciBERT (Scientific Bidirectional Encoder Representations from Transformers), and structural geometry via a GVP-GNN (Geometric Vector Perceptron Graph Neural Network) applied to AlphaFold2 contact graphs. Evaluation on datasets from STITCH, STRING, and PubMed shows that MM-TCoCPIn achieves state-of-the-art performance (AUC = 0.93, F1 = 0.92), outperforming uni-modal baselines. Importantly, ablation and counterfactual analyses confirm that each modality contributes distinct biological insight: topology ensures robustness, semantics enhance recall, and structure sharpens precision. This framework offers a scalable and causally interpretable solution for CPI modeling, bridging the gap between predictive accuracy and mechanistic understanding. Full article

The 2022 global mpox outbreak highlighted the risk of sustained human-to-human transmission of monkeypox virus (MPXV) in non-endemic regions, yet genomic surveillance in Asia, particularly in China, remains limited. This study conducted horizontal genomic surveillance of MPXV in Shenzhen from 2023 to 2024 to characterize the phylogenetic structure, mutational patterns, and adaptive evolution of locally circulating strains. Phylogenetic analysis showed 95.2% of strains belonged to the dominant lineage C.1.1, with 4.8% in lineage E.3, forming three distinct genetic clusters that indicate multiple independent introductions and established local transmission chains. Whole-genome mutational analysis identified 146 single-nucleotide polymorphisms (SNPs), 81.5% of which carried APOBEC3-mediated mutation signatures (TC > TT and GA > AA), reflecting host-driven antiviral editing. Notably, dynamic changes in low-complexity regions (LCRs) were observed, implying potential roles in genome plasticity and adaptive evolution. Functional analysis revealed non-synonymous substitution biases in host-interacting proteins OPG064, OPG145, and OPG210, while replication protein OPG105 remained conserved. Structural modeling identified critical substitutions in OPG002 (S54F), OPG016 (R84K), and OPG036 (R48C) that may enhance immune evasion by modulating TNF-α signaling, NKG2D engagement, and Type I interferon antagonism. These findings illuminate unique MPXV evolutionary dynamics in Shenzhen, emphasizing continuous genomic surveillance for non-endemic outbreak preparedness. Full article

Herbs offer people not just sustenance and housing but also serve as a key supplier of pharmaceuticals. This research is designed to assess the antioxidant and antidiabetic properties of green-produced zirconium dioxide and magnesium oxide nanoparticles (ZrO₂ and MgO NPs) utilizing extracts from unripe Solanum trilobatum fruit. ZrO₂ and MgO NPs have garnered considerable interest owing to their superior bioavailability, lower toxicity, and many uses across the healthcare and commercial industries. Scientific approaches, such as diverse spectroscopic and microscopic approaches, validated the creation of agglomerated spherical ZrO₂ and MgO NPs, measuring between 15 and 30 and 60 and 80 nm, with a mixed-phase composition consisting of monoclinic and tetragonal phases for ZrO₂ and a face-centered cubic structure for MgO NPs. UV–vis studies revealed a distinct peak at 378 and 290 nm for ZrO₂ and MgO NPs, suggesting efficient settling through the phytonutrients in S. trilobatum. The antioxidant capacity of ZrO₂ and MgO NPs was evaluated utilizing DPPH and FRAP reducing power assays. The diabetic effectiveness of ZrO₂ and MgO NPs was examined by alpha-amylase and alpha-glucosidase assays. The optimum doses of 500 and 1000 μg/mL were shown to be efficient in reducing radical species. Green-produced ZrO₂ and MgO NPs exhibited a dose-dependent reaction, with greater amounts of ZrO₂ and MgO NPs exerting a more pronounced inhibitory effect on the catalytic sites of enzymes. This work suggests that ZrO₂ and MgO NPs may attach to charge-carrying entities and function as rival inhibitors, therefore decelerating the enzyme–substrate reaction and inhibiting enzymatic degradation. Molecular docking analysis of ZrO₂ and MgO NPs with three proteins (2F6D, 2QV4, and 3MNG) implicated in antidiabetic and antioxidant studies demonstrated the interaction of ZrO₂ and MgO NPs with the target proteins. The results indicated the in vitro effectiveness of phytosynthesized ZrO₂ and MgO NPs as antidiabetic antioxidant agents, which may be used in the formulation of alternative treatment strategies against diabetes and oxidative stress. In summary, the green production of ZrO₂ and MgO NPs with Solanum trilobatum unripe fruit extract is an efficient, environmentally sustainable process that yields nanomaterials with significant antioxidant and antidiabetic characteristics, underscoring their prospective uses in biomedical research. Full article

The integration of emulsion gels in 3D food printing has emerged as a promising strategy to enhance both the structural fidelity and functional performance of printed foods. Emulsion gels, composed of proteins, polysaccharides, lipids, and their complexes, can provide tunable rheological and mechanical properties suitable for extrusion and shape retention. This review explores the formulation strategies, including phase behavior (O/W, W/O, and double emulsions); stabilization methods; and post-printing treatments, such as enzymatic, ionic, and thermal crosslinking. Advanced techniques, including ultrasound and high-pressure homogenization, are highlighted for improving gel network formation and retention of active compounds. Functional applications are addressed, with a focus on meat analogs, bioactive delivery systems, and personalized nutrition. Furthermore, the role of the oil content, interfacial engineering, and protein–polysaccharide interactions in improving print precision and post-processing performance is emphasized. Despite notable advances, challenges remain in scalability, regulatory compliance, and optimization of print parameters. The integration of artificial intelligence can also provide promising advances for smart design, predictive modeling, and automation of the 3D food printing workflow. Full article

Cell–cell communication and extracellular matrix (ECM) organization in a bone microenvironment are essential to replicate the bone microenvironment accurately. In this study, the extracellular matrix (ECM) was emulated by incorporating M13 phages, selected through phage display for displaying engineered peptides that mimic bone matrix proteins, into human osteoblast cultures to develop a three-dimensional bone model (3D BMP-Phage). Comprehensive analysis was performed to investigate: (i) the morphological development of spheroids, assessed by optical microscopy and quantified via fractal dimension analysis using box-counting algorithms; (ii) the biochemical composition of the extracellular matrix, evaluated by Raman spectroscopy; (iii) ECM protein deposition, analyzed through immunofluorescence staining; (iv) matrix mineralization, assessed by Alizarin Red staining and alkaline phosphatase (ALP) activity assay; and (v) osteogenic gene expression, measured by quantitative RT-PCR. The findings demonstrate that the 3D BMP-Phage model, facilitated by a cocktail of bone-mimicking peptides, enhances structural integrity, ECM complexity, mineralization, and osteogenic pathways compared to the control. This novel approach replicates key aspects of the bone microenvironment, providing a valuable platform for advanced physiological and regenerative medicine research under controlled conditions. Full article

In response to the growing demand for sustainable biomaterials in tissue engineering, we investigated the potential of structurally intact brown seaweed scaffolds derived from Laminaria digitata (L.D.) and Laminaria saccharina (L.S.), produced by a detergent-free, visible-light decellularization process aimed at preserving structural integrity. Blades were submerged in cold flow-through and aerated water with red (620 nm) and blue (470 nm) light exposure for 4 weeks. Histology, scanning electron microscopy (SEM), and micro-computed tomography (micro-CT) analyses demonstrated that the light decellularization process removed cells/debris, maintained essential structural features, and significantly increased scaffold porosity. Mechanical property analysis through tensile testing revealed a substantial increase in tensile strength post decellularization, with L.D. scaffolds increasing from 3.4 MPa to 8.7 MPa and L.S. scaffolds from 2.1 MPa to 6.6 MPa. Chemical analysis indicated notable alterations in polysaccharide and protein composition following decellularization. Additionally, scaffolds retained high swelling and fluid absorption capacities, critical for biomedical uses. These findings underscore that the decellularized L.D. and L.S. scaffolds preserved structural integrity and exhibited enhanced mechanical properties, interconnected porous structures, and significant liquid retention capabilities, establishing them as promising biomaterial candidates for soft-tissue reinforcement, wound care, and broader applications in regenerative medicine. Full article

Background: Transcription factors (TFs) critically regulate gene expression, orchestrating plant growth, development, and stress responses. The conserved IDD (INDETERMINATE DOMAIN) TF family modulates key developmental processes, including root, stem, and seed morphogenesis. Dendrocalamus latiflorus Munro, an economically vital sympodial bamboo in southern China, suffers significant yield losses due to prevalent bamboo shoot abortion, impacting both edible shoot production and timber output. Despite the documented roles of IDD TFs in shoot apical meristem expression and lateral organ regulation, their genome-wide characterization in D. latiflorus remains unstudied. Methods: Using IDD members from Arabidopsis thaliana, Oryza sativa, and Phyllostachys edulis as references, we identified 45 DlIDD genes in D. latiflorus. Comprehensive bioinformatics analyses included gene characterization, protein physicochemical assessment, phylogenetic reconstruction, and examination of gene structures/conserved domains. Differential expression of DlIDD genes was profiled between dormant and sprouting bamboo shoots to infer putative functions. Results: The 45 DlIDD genes were phylogenetically classified into three subfamilies and unevenly distributed across 34 chromosomes. Whole-genome duplication (WGD) events drove the expansion of this gene family. Promoter analyses revealed enriched cis-regulatory elements associated with hormone response and developmental regulation. Functional analyses suggested potential roles for DlIDD genes in bamboo shoot development. Conclusions: This study provides a foundation for future research to elucidate the functions of IDD TFs and their regulatory mechanisms in bamboo shoot morphogenesis and lateral bud development within woody monocots. Full article

Authorized SARS-CoV-2 vaccines elicit both antibody and T-cell responses; however, benchmark correlates and update decisions have largely emphasized neutralizing antibodies. Motivated by the complementary role of cellular immunity, we designed a prototype polyepitope DNA vaccine encoding conserved human and mouse T-cell epitopes from non-structural proteins of the original strain SARS-CoV-2 lineage. Epitope selection was guided by in silico predictions for common HLA class I alleles in the Brazilian population and the mouse H-2Kb haplotype. To enhance immunogenicity, the polyepitope sequences were fused to glycoprotein D (gD) from Herpes Simplex Virus 1 (HSV-1), an immune activator of dendritic cells (DCs), leading to enhanced activation of antigen-specific T-cell responses. Mice were immunized with two doses of the electroporated DNA vaccine encoding the gD-fused polyepitope, which induced robust interferon-gamma– and tumor necrosis factor-alpha–producing T cell responses compared to control mice. In addition, K18-hACE2 transgenic mice showed protection against intranasal challenge with the original SARS-CoV-2 strain, with reduced clinical symptoms, less weight loss, and decreased viral burden in both lung and brain tissues. The results experimentally confirm the protective role of T cells in vaccine-induced protection against SARS-CoV-2 and open perspectives for the development of universal anti-coronavirus vaccines. Full article

A comprehensive analysis of the molecular epidemiology of SARS-CoV-2 in the Kandy District of Sri Lanka from November 2020 to March 2022 was conducted to address the limited genomic surveillance data available across the country. The study investigated the circulating SARS-CoV-2 lineages, their temporal dynamics, and the associated mutational profiles in the study area. A total of 280 SARS-CoV-2-positive samples were selected, and 252 complete genomes were successfully sequenced using Oxford Nanopore Technology. Lineage classification was performed using the EPI2ME tool, while phylogenetic relationships were inferred through maximum likelihood and time-scaled phylogenetic trees using IQ-TREE2 and BEAST, respectively. Amino acid substitutions were analyzed to understand lineage-specific mutation patterns. Fifteen SARS-CoV-2 lineages were identified, and of those B.1.411 (36%) was the most prevalent, followed by Q.8 (21%), AY.28 (9.5%), and the Delta and Omicron variants. The lineage distribution showed a temporal shift from B.1.411 to Alpha, Delta, and finally the Omicron, mirroring the global trends. Time to the most recent common ancestor analyses provided estimates for the introduction of major variants, while mutation analysis revealed the widespread occurrence of D614G in the spike protein and lineage-specific mutations across structural, non-structural, and accessory proteins.Detection of the Epsilon variant (absent in other national-level studies) in November 2020, highlighted the regional heterogeneity viral spread. This study emphasizes the importance of localized genomic surveillance to capture the true diversity and evolution of SARS-CoV-2, to facilitate containment strategies in resource-limited settings. Full article

Q-type C2H2 zinc finger protein (ZFP) transcription factors, a plant-specific subfamily of C2H2 ZFP, have been implicated in regulating abiotic stress responses, growth, and developmental processes in plants. Rapeseed (Brassica napus L.) is a crucial oil crop widely used for the production of high-quality vegetable oil, animal feed, and biodiesel. Compared with studies on Q-type C2H2-ZFP genes in other plant species, systematic research has not been performed in B. napus. In this study, a comprehensive genome-wide analysis of Q-type C2H2-ZFPs in B. napus was conducted. A total of 216 Q-type C2H2-ZFP genes were identified, exhibiting extensive and uneven distribution across the 19 chromosomes. Phylogenetic analysis, based on homologs from Arabidopsis, classified these genes into eight distinct subfamilies, with each containing one to three conserved “QALGGH” motifs. Each subfamily exhibited similar motif compositions and gene structures. Evolutionary studies revealed that segmental duplication events played a crucial role in the expansion of the BnaQ-type C2H2-ZFP gene family. Expression pattern analysis in different tissues and under abiotic stress identified BnaA03g09250D, BnaC09g35160D, BnaC03g11570D, and BnaA10g25850D as candidate genes involved in the response to freezing stress. Overexpression of BnaC09g35160D provided preliminary evidence that it enhances freezing tolerance in plants. This comprehensive study of Q-type C2H2-ZFPs in B. napus will enhance our understanding of the BnaQ-type C2H2-ZFP gene family and provide valuable insights for further functional investigations of BnaC09g35160D. Full article