Search Results (371)

Icariin (ICA) is widely recognized for its health benefits. In this work, we examined the intermolecular interactions between ICA and proteinase K (PK) via multi-spectroscopic techniques and molecular simulations. The experimental findings revealed that ICA quenched the fluorescence emission of PK by forming a noncovalent complex. Both hydrogen bonding and van der Waals interactions are essential for the complex’s formation. Then Förster resonance energy transfer (FRET), competitive experiments, and synchronous fluorescence spectroscopy were adopted to verify the formation of the complex. Molecular docking studies demonstrated that ICA could spontaneously bind to PK by hydrogen bonding and hydrophobic interactions, which is consistent with the spectroscopic results. The PK-ICA complex’s dynamic stability was evaluated using a 50 ns molecular dynamics (MD) simulation. The simulation results revealed no significant structural deformation or positional changes throughout the entire simulation period. The complex appears to be rather stable, as seen by the average root-mean-square deviation (RMSD) fluctuations for the host protein in the PK-ICA complex of 1.08 Å and 3.09 Å. These outcomes of molecular simulations suggest that ICA interacts spontaneously and tightly with PK, consistent with the spectroscopic findings. The approach employed in this research presents a pragmatic and advantageous method for examining protein–ligand interactions, as evidenced by the concordance between empirical and theoretical findings. Full article

The inherent hydrophobic nature of PVDF material renders it challenging to establish a stable aqueous hydration layer, thereby limiting its suitability as a substrate for the preparation of nanofiltration (NF) membranes. In this study, we developed a novel modification approach that effectively enhances the hydrophilicity of PVDF substrates through the incorporation of sulfonic acid-doped polyaniline (SPANI) and hyperbranched polyester (HPE) into the PVDF casting solution, followed by cross-linking with trimesoyl chloride (TMC). The introduction of SPANI and HPE, which contain reactive polar amino and hydroxyl groups, improved the hydrophilicity of the substrate, while the subsequent cross-linking with TMC effectively anchored these components within the substrate through the covalent linking between TMC and the reactive sites. Additionally, the hydrolysis of TMC yielded non-reactive carboxyl groups, which further enhanced the hydrophilicity of the substrate. As a result, the modified PVDF substrate exhibited improved hydrophilicity, facilitating the construction of an intact polyamide layer. In addition, the fabricated TFC NF membrane demonstrated excellent performance in the advanced treatment of tap water, achieving a total dissolved solid removal rate of 57.9% and a total organic carbon removal rate of 85.3%. This work provides a facile and effective route to modify PVDF substrates for NF membrane fabrication. Full article

The bis-thiourea chiral solvating agent (CSA) BTDA enables the NMR-based determination of absolute configuration in N-3,5-dinitrobenzoyl (DNB) amino acid derivatives without requiring covalent derivatization. A reliable trend of the sense of nonequivalence and absolute configuration is found in both ¹H and ¹³C NMR spectra. A dual-enantiomer approach, using (R,R)- and (S,S)-BTDA, generates diastereomeric complexes with the enantiopure substrate, and distinct spatial arrangements are reflected in consistent and interpretable Δδ values. The observed chemical shift differences correlate reliably with the stereochemistry of the chiral center and are further supported by ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) experiments and binding constants’ measurements, confirming the formation of stereoselective non-covalent complexes. This methodology extends the logic of Mosher’s analysis to solvating agents and remains effective even in samples containing single pure enantiomers of the amino acid derivative. The BTDA-based dual-CSA system thus represents a robust, non-derivatizing strategy for stereochemical assignment by NMR, combining operational simplicity with broad applicability to DNB derivatives of amino acids with free carboxyl function. Full article

Cyclic voltammetry (CV) is an accessible, readily available, non-expensive technique that can be used to search for the interaction of compounds with DNA and detect the strongest DNA-binding from a set of compounds, therefore allowing for the optimization of the number of cytotoxicity assays. Focusing on this electrochemical approach, the study of twenty-seven camphorimine silver complexes of six different families was performed aiming at detecting interactions with calf thymus DNA (CT-DNA). All of the complexes display at least two cathodic waves attributed respectively to the Ag(I)→Ag(0) (higher potential) and ligand based (lower potential) reductions. In the presence of CT-DNA, a negative shift in the potential of the Ag(I)→Ag(0) reduction was observed in all cases. Additional changes in the potential of the waves, attributed to the ligand-based reduction, were also observed. The formation of a light grey product adherent to the Pt electrode in the case of {Ag(OH)} and {Ag₂(µ-O)} complexes further corroborates the interaction of the complexes with CT-DNA detected by CV. The morphologic analysis of the light grey material was made by scanning electronic microscopy (SEM). The magnitude of the shift in the potential of the Ag(I)→Ag(0) reduction in the presence of CT-DNA differs among the families of the complexes. The complexes based on {Ag(NO₃)} exhibit higher potential shifts than those based on {Ag(OH)}, while the characteristics of the ligand (^AL-Y, ^BL-Y, ^CL-Z) and the imine substituents (Y,Z) fine-tune the potential shifts. The energy values calculated by docking corroborate the tendency in the magnitude of the interaction between the complexes and CT-DNA established by the reaction coefficient ratios (Q_[Ag-DNA]/Q_[Ag]). The molecular docking study extended the information regarding the type of interaction beyond the usual intercalation, groove binding, or electrostatic modes that are typically reported, allowing a finer understanding of the non-covalent interactions involved. The rationalization of the CV and cytotoxicity data for the Ag(I) camphorimine complexes support a direct relationship between the shifts in the potential and the cytotoxic activities of the complexes, aiding the decision on whether the cytotoxicity of a complex from a family is worthy of evaluation. Full article

Seafood (fish, crustacean, and mollusk) allergy represents a critical global health issue. Food processing offers a viable strategy for allergenicity mitigation and serves as a critical intervention for seafood allergy prevention. This paper reviews recent advances in seafood allergen research, with particular focus on molecular properties, epitopes, and structure–allergenicity relationships, which are foundations for designing processing technologies to mitigate allergenicity. Furthermore, an analysis of how various food processing techniques modulate allergen structures and epitopes, ultimately affecting their allergenicity, was conducted. Current World Health Organization (WHO)/International Union of Immunological Societies (IUIS) listings include 44 fish allergens and 60 shellfish allergens, with their characterization enabling targeted processing approaches for allergenicity elimination. Physical processing techniques, including thermal and non-thermal treatment, can dramatically influence the conformational and linear epitopes by altering or destroying the structure of an allergen. Chemistry-based processing techniques (enzymatic-catalyzed cross-linking and glycation), which induce covalent/non-covalent interactions between allergens and various modifiers, can effectively mask epitopes through molecular complexation. Biological processing attenuates allergenicity by inducing protein unfolding, polypeptide chain uncoiling, and enzymatic degradation. Nevertheless, the structure–activity relationship of seafood allergens remains insufficiently elucidated, despite its critical role in guiding processing technologies for allergenicity elimination and elucidating the fundamental mechanisms involved. Full article

Polymethyl methacrylate (PMMA) is a polymer with excellent properties for water remediation. Understanding the molecular interactions between pharmaceuticals, such as β-blockers, and PMMA is essential for optimizing purification technologies. Atomistic calculations provide a detailed understanding of the interaction between molecules without the need for expensive equipment. This study presents a computational analysis of how PMMA interacts with salbutamol and atenolol. Geometrical optimizations were performed using semiempirical and density functional theory (DFT) calculations. To identify interactions between PMMA and pharmaceuticals, we employed the reduced density gradient (RDG) approach, providing insight into intramolecular noncovalent interactions between PMMA’s atoms and pharmaceuticals. Full article

Coronaviruses (CoVs) have recently emerged as significant causes of respiratory disease outbreaks, with the novel coronavirus pneumonia of 2019, known as COVID-19, being highly infectious and triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding virus–host interactions and molecular targets in host cell death signalling is crucial for inhibitor development. Among the promising targets for inhibitor development is the main protease (Mpro), which is essential for viral replication. While current research has focused mainly on covalent inhibitors, growing attention is being given to non-covalent inhibitors due to their potential for lower toxicity and improved resistance to viral mutations. This literature review provides an in-depth analysis of recent in silico approaches used to identify and optimise non-covalent inhibitors of SARS-CoV-2 Mpro. It focuses on molecular docking and robust molecular dynamics (MD) simulation technologies to discover novel scaffolds with better binding affinities. The article summarises recent studies that pre-screened several potential non-covalent inhibitors, including natural constituents like alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones, using in silico methods. The in silico approach, pivotal to developing small molecules of Mpro non-covalent inhibitors, provides an efficient avenue to guide future research efforts toward developing high-performance Mpro inhibitors for SARS-CoV-2 Mpro, representing the latest advancements in drug design. Full article

Nitrogen and sulfur-co-doped carbon dots (N, S-CDs) were synthesized using a simple, eco-friendly hydrothermal technique with L-cysteine as the precursor. The synthesis approach produced highly water-dispersible, heteroatom-doped CDs with surface functional groups comprising amine, carboxyl, thiol, and sulfonic acid. Data analysis of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM) confirmed their amorphous nature, nanoscale dimensions (1–8 nm, average particle size of 2.6 nm), and surface chemistry. Optical examination revealed intense and pure blue fluorescence emission under UV excitation, with excitation-dependent emission behavior attributed to surface defects and heteroatom doping. The N, S-CDs were applied as fluorescent probes for detecting perfluorooctanesulfonic acid (PFOS), a notable component of the perfluoroalkyl substances (PFAS) family, demonstrating pronounced and concentration-dependent fluorescence quenching. A linear detection range of 3.33–20 µM and a limit of detection (LOD) of 2 µM were reported using the N, S-CDs probe. UV-Vis spectral shifts and dye-interaction investigations indicated that the sensing mechanism is regulated by non-covalent interactions, primarily electrostatic and hydrophobic forces. These findings confirm the potential of N, S-CDs to be used as effective optical sensors for detecting PFOS in environmental monitoring applications. Full article

Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, are pivotal regulators of gene expression and contributors to disease pathogenesis. This study elucidated the biogenesis, functional significance, and regulatory network of circRNA_4083, a novel exon-derived circRNA originating from exons 22 and 23 of the MSH3 gene in chicken. Through comprehensive molecular characterization—including Sanger sequencing, RNase R digestion assays, and subcellular localization—we confirmed the robust stability and predominant cytoplasmic localization of circRNA_4083 across diverse chicken tissues. Mechanistic investigations revealed that reverse complementary sequences within flanking intronic regions are indispensable for its circularization, as demonstrated by overexpression plasmids (#1–#4) in DF-1 cells. Functional analyses demonstrated that circRNA_4083 significantly inhibited cell apoptosis and increased cellular viability. Integrative bioinformatics approaches predicted a competing endogenous RNA (ceRNA) network comprising 12 miRNAs and 2132 target genes (FDR < 0.05), with significant enrichment in pathways critical to genomic stability, including non-homologous end joining (NHEJ) and ubiquitin-mediated proteolysis. These findings position circRNA_4083 as a key modulator of cellular viability and genomic integrity, with potential implications for avian leukosis virus-J (ALV-J) pathogenesis and resistance breeding strategies. This work advances our understanding of circRNA-driven regulatory mechanisms in avian species and underscores their relevance in poultry health. Full article

Two-dimensional nanomaterials (2DNMs) exhibit significant potential for the development of functional and specifically targeted biosensors, owing to their unique planar nanosheet structures and distinct physical and chemical properties. Biomodification and biomimetic synthesis offer green and mild approaches for the fabrication of multifunctional nanohybrids with enhanced catalytic, fluorescent, electronic, and optical properties, thereby expanding their utility in constructing high-performance biosensors. In this review, we present recent advances in the synthesis of 2DNM-based nanohybrids via both biomodification and biomimetic strategies for biosensor applications. We discuss covalent and non-covalent biomodification methods involving various biomolecules, including peptides, proteins, DNA/RNA, enzymes, biopolymers, and bioactive polysaccharides. The engineering of biomolecule–nanomaterial interfaces for the creation of biomodified 2DNM-based nanohybrids is also explored. Furthermore, we summarize the biomimetic synthesis of 2DNM-based bio–nanohybrids through pathways such as bio-templating, biomolecule-directed self-assembly, biomineralization, and biomimetic functional integration. The potential applications of these nanohybrids in diverse biosensing platforms—including colorimetric, surface plasmon resonance, electrochemical, fluorescence, photoelectrochemical, and integrated multimodal biosensors—are introduced and discussed. Finally, we analyze the opportunities and challenges associated with this rapidly developing field. We believe this comprehensive review will provide valuable insights into the biofunctionalization of 2DNMs and guide the rational design of advanced biosensors for diagnostic applications. Full article

Precise separation and antifouling capabilities are critical for the application of membrane separation technology. In this work, we developed a multiplayer layer-by-layer assembly strategy to sequentially deposit tannic acid (TA) and lysozyme (Lys) onto polyethersulfone/iron (PES/Fe) ultrafiltration membrane substrates, enabling the simple and efficient fabrication of a biofouling-resistant loose nanofiltration (LNF) membrane with superior dye/salt separation performance. This approach fully leverages the multifunctionality of TA by exploiting its coordination with Fe³⁺ and non-covalent interactions with Lys. The obtained PES/Fe-TA-Lys LNF membrane exhibits a pure water flux of 57.5 L·m⁻²·h⁻¹, along with exceptional dye rejection rates (98.3% for Congo Red (CR), 99.2% for Methyl Blue (MB), 98.4% for Eriochrome Black T (EBT), and 67.6% for Acid Orange 74 (AO74)) while maintaining minimal salt retention (8.2% for Na₂SO₄, 4.3% for MgSO₄, 3.5% for NaCl, and 2.4% for MgCl₂). The PES/Fe-TA-Lys LNF membrane also displays outstanding antifouling performance against bovine serum albumin (BSA), humic acid (HA), and CR, along with strong biofouling resistance against Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) via synergistic anti-adhesion and biofilm inhibiting effects. This work presents a novel and scalable approach to fabricating biofouling-resistant LNF membranes, offering great potential for dye/salt separation in textile wastewater treatment. Full article

The SARS-CoV-2 main protease (Mpro), essential for viral replication, remains a prime target for antiviral drug design against COVID-19 and related coronaviruses. In this study, we present a systematic investigation into the molecular determinants of Mpro inhibition using an integrated approach combining large-scale data mining, cheminformatics, and quantum chemical calculations. A curated dataset comprising 963 high-resolution structures of Mpro–ligand complexes—348 covalent and 615 non-covalent inhibitors—was mined from the Protein Data Bank. Cheminformatics analysis revealed distinct physicochemical profiles for each inhibitor class: covalent inhibitors tend to exhibit higher hydrogen bonding capacity and sp³ character, while non-covalent inhibitors are enriched in aromatic rings and exhibit greater aromaticity and lipophilicity. A novel descriptor, Weighted Hydrogen Bond Count (WHBC), normalized for molecular size, revealed a notable inverse correlation with aromatic ring count, suggesting a compensatory relationship between hydrogen bonding and π-mediated interactions. To elucidate the energetic underpinnings of molecular recognition, 40 representative inhibitors (20 covalent, 20 non-covalent) were selected based on principal component analysis and aromatic ring content. Quantum mechanical calculations at the double-hybrid B2PLYP/def2-QZVP level quantified non-bonded interaction energies, revealing that covalent inhibitors derive binding strength primarily through hydrogen bonding (~63.8%), whereas non-covalent inhibitors depend predominantly on π–π stacking and CH–π interactions (~62.8%). Representative binding pocket analyses further substantiate these findings: the covalent inhibitor F2F-2020198-00X exhibited strong hydrogen bonds with residues such as Glu166 and His163, while the non-covalent inhibitor EDG-MED-10fcb19e-1 engaged in extensive π-mediated interactions with residues like His41, Met49, and Met165. The distinct interaction patterns led to the establishment of pharmacophore models, highlighting key recognition motifs for both covalent and non-covalent inhibitors. Our findings underscore the critical role of aromaticity and non-bonded π interactions in driving binding affinity, complementing or, in some cases, substituting for hydrogen bonding, and offer a robust framework for the rational design of next-generation Mpro inhibitors with improved selectivity and resistance profiles. Full article

The human CHCHD4 protein, which is a prototypical family member, carries a coiled–coil–helix–coiled–coil–helix motif that is stabilized by two disulfide bonds. Using its CPC sequence motif, CHCHD4 plays a key role in mitochondrial metabolism, cell survival, and response to stress conditions, controlling the mitochondrial import of diversified protein substrates that are specifically recognized through an interplay between covalent and non-covalent interactions. In the present review, we provide an updated and comprehensive analysis of CHCHD4 substrates controlled by its redox activities. A particular emphasis has been placed on the molecular and structural aspects of these partnerships. The literature survey has been integrated with the mining of structural databases reporting either experimental structures (Protein Data Bank) or structures predicted by AlphaFold, which provide protein three-dimensional models using machine learning-based approaches. In providing an updated view of the thirty-four CHCHD4 substrates that have been experimentally validated, our analyses highlight the notion that this protein can operate on a variety of structurally diversified substrates. Although in most cases, CHCHD4 plays a crucial role in the formation of disulfide bridges that stabilize helix–coil–helix motifs of its substrates, significant variations on this common theme are observed, especially for substrates that have been more recently identified. Full article

(1) Background: Circular RNAs (circRNAs) are covalently closed single-stranded molecules that play crucial roles in gene regulation, while microRNAs (miRNAs), specifically mature microRNAs, are naturally occurring small molecules of non-coding RNA with 17-25-nucleotide sizes. Understanding circRNA–miRNA interactions (CMIs) can reveal new approaches for diagnosing and treating complex human diseases. (2) Methods: In this paper, we propose a novel approach for predicting CMIs based on a graph attention network (GAT). We utilized DNABERT to extract molecular features of the circRNA and miRNA sequences and role-based graph embeddings generated by Role2Vec to extract the CMI features. The GAT’s ability to learn complex node dependencies in biological networks provided enhanced performance over the existing methods and the traditional deep neural network models. (3) Results: Our simulation studies showed that our GAT model achieved accuracies of 0.8762 and 0.8837 on the CMI-9905 and CMI-9589, respectively. These accuracies were the highest among the other existing CMI prediction methods. Our GAT method also achieved the highest performance as measured by the precision, recall, F1-score, area under the receiver operating characteristic (AUROC) curve, and area under the precision–recall curve (AUPR). (4) Conclusions: These results reflect the GAT’s ability to capture the intricate relationships between circRNAs and miRNAs, thus offering an efficient computational approach for prioritizing potential interactions for experimental validation. Full article

The transcription factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular defense mechanisms against oxidative stress and inflammation. Keap1 (Kelch-like ECH-associated protein 1) regulates Nrf2 activity by ubiquitination-mediated cytoplasmic retention, thereby suppressing its nuclear translocation and subsequent transcriptional activation of genes encoding phase II detoxifying enzymes. Using a structure-based virtual screening approach, we screened ~16,000 natural compounds to identify Keap1-Nrf2 PPI inhibitors. Nine compounds were identified based on their high binding affinities and favorable interactions with Keap1, primarily through non-covalent interactions. To validate the binding stability of these inhibitors, molecular dynamics (MD) simulations were performed, confirming the robustness of the Keap1–inhibitor complexes over time. Subsequent in vitro assays on human epithelial keratinocyte cells (HaCaT) revealed that six of these compounds notably upregulated Nrf2 mRNA expression, regis tering increases from 23% to 50% in comparison to the control. Notably, chebulinic acid emerged as the most potent compound, demonstrating the greatest elevation in Nrf2 expression. Penetration studies further showed that chebulinic acid, when encapsulated in silk fibroin, achieved a 0.14% penetration rate after 24 h though it could not penetrate into the stratum corneum alone. This result highlighted the potential of chebulinic acid in the use of anti-aging skincare formulations. Collectively, our findings affirmed that molecular docking is a reliable and effective approach for the identification of novel anti-aging agents targeting the Keap1-Nrf2 pathway. Full article