Search Results (185)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem cell disease characterized primarily by intravascular hemolysis, thrombosis, and bone marrow failure. Complement inhibitors are commonly used in clinical treatment and show limited efficacy, highlighting the urgent need to identify new therapeutic targets and explore alternative treatment strategies to provide theoretical guidance for clinical practice. Methods: We established a PNH cell model and constructed an miRNA–mRNA regulatory network to identify key miRNAs and core target genes. Single-cell sequencing data were analyzed to further clarify the critical genes. Finally, integrated drug database analysis identified potential therapeutic agents for PNH, which were validated by molecular docking and molecular dynamics simulations. Results: Using CRISPR/RNP technology, we successfully constructed a PIGA-knockout (PIGA-KO) THP-1 cell model. Differential expression analysis identified 1979 differentially expressed mRNAs (DEmRNAs) and 97 differentially expressed miRNAs (DEmiRNAs). The multiMiR package in R was used to predict the target genes of DEmiRNAs, from which those experimentally validated through dual-luciferase reporter assays were selected. After integration with the DEmRNAs, an miRNA–mRNA regulatory network was constructed, comprising 26 miRNAs and 38 mRNAs. Subsequent miRNA pathway enrichment analysis identified hsa-miR-23a-3p as a key miRNA, with CXCL12, CXCL8, HES1, and TRAF5 serving as core target genes. The integration of single-cell sequencing datasets (PRJNA1061334 and GSE157344) was performed, followed by cell communication and enrichment analysis. This approach, combined with clinical relevance, identified the neutrophil cluster as the key cluster. Intersection analysis of neutrophil cluster differential analysis results with key modules from hdWGCNA further clarified the critical genes. Drug prediction using EpiMed, CMap, and DGIdb identified Leflunomide, Dipyridamole, and Pentoxifylline as potential therapeutic agents. Molecular docking and molecular dynamics simulations showed stable binding of these potential drugs to the critical molecules, indicating a viable molecular interaction foundation. Conclusions: Leflunomide, Dipyridamole, and Pentoxifylline may serve as promising therapeutic agents for PNH, and the hsa-miR-23a-3p/CXCL8 regulatory axis could play a pivotal role in the pathogenesis and progression of PNH. Full article

Background: Recently, compounds such as pyrimidine, pyridazine, 1,2,4-triazepine, 1,3,4,6-oxatriazepine, pyridazino[1,2-a]pyrimidine, and pyridazino[1,2-c] pyrimidine, as well as their derivatives, have attracted attention due to their diverse biological activities. Objective: This study focuses on the synthesis of new heterocyclic compounds that feature a seven-membered ring, including pyridazinopyrimido[2,1-c] [1,2,4]triazepine-tetraones (4), pyridazinopyrimidotriazepine-triones (5–8), aminopyri-dazinopyrimido[2,1-c][1,2,4]triazepine-tetraone (9), and 6-amino-8-imino-pyridazino pyrimido[2,1-c] [1,2,4]triazepine-trione (10). These new compounds were synthesized starting from 1-(4-oxo-1,4-dihydropyrimidine)-1,2-dihydropyridazine-3,6-dione (3) and were then evaluated for their antimicrobial activity. Methods: A new series of pyridazino[1,2-a]pyrimido[2,1-c][1,2,4]triazepines and 1,3,4,6-oxatriazepines were synthesized using modern techniques and advanced technology, achieving yields between 72% and 90%. Results: All new compounds were confirmed through IR, ¹H NMR, ¹³C NMR, and mass spectroscopy (MS) and tested for in vitro antimicrobial activity. Compounds (8-10) exhibited excellent antimicrobial activity. Computational analysis provided a comprehensive evaluation of the broad-spectrum inhibitory potential of four lead compounds (6, 8, 9, and 10) against key microbial and fungal targets. These compounds demonstrated consistently superior binding affinities compared to control drugs cefotaxime and nystatin across a range of enzymes essential for pathogen viability and virulence. Conclusions: The structure–activity relationship (SAR) study established a correlation between the tested compounds and their antimicrobial activity. Molecular docking analysis indicated that the in silico results strongly suggest that compounds (6, 8, 9, and 10) are promising multi-target agents capable of disrupting essential bacterial processes and critical fungal pathways, making them excellent candidates for the development of novel antimicrobial therapeutics. These consistent findings support the conclusion that both practical and theoretical studies of the new compounds align with their antimicrobial effectiveness. Full article

One significant trend in the research of plant treatment methods is that regarding the use of natural-based methods in plant protection. In this study, antimicrobial activity and changes in MdPR10 gene expression were tested for a total of five plant pathogens in a model of apple fruits, where strawberry and ivy EOs were used. The vapor-phase chemical composition of both EOs was profiled using HS-GC-MS. qRT-PCR was applied for a bacterial response analysis, together with disk diffusion assays, and minimum inhibitory concentrations were determined. To elucidate the molecular basis of the antibacterial potential of essential oils (EOs), docking analyses were performed. For Xanthomonas arboricola and Pectobacterium carotovorum, the presence of EOs resulted in the downregulation of MdPR10. Strawberry EO was more effective against weakly virulent strains of bacteria; ivy EO had greater inhibitory effects. HS-GC-MS detected 13 volatiles in strawberry EO—dominated by ethyl butyrate, ethyl 2-methylbutanoate, ethyl hexanoate, and ethyl 3-methylbutanoate—and 16 in ivy EO, characterized by monoterpenes and monoterpenoids with 1,8-cineole as the principal component. P-cymene showed the most potent binding activity against D-alanine–D-alanine ligase. Ivy EO has the potential to be effective as a natural preservative alternative mainly in postharvest technology. Full article

Zinc oxide nanoparticles (ZnO NPs) are increasingly applied in medicine, cosmetics, and environmental technologies, yet their interactions with blood cells remain poorly understood, raising cross-species safety concerns. Using frog (nucleated) and human (anucleate) erythrocytes as comparative models, we show that cellular architecture fundamentally shapes responses to ZnO NPs exposure. Human erythrocytes exhibited a dose-dependent progression from membrane deformation to eryptosis and hemolysis, reflecting the pronounced vulnerability of anucleate cells. In contrast, frog erythrocytes sustained nuclear DNA damage while largely preserving membrane integrity, highlighting the protective or reparative role of the nucleus. Molecular docking revealed energetically favorable interactions of ZnO NPs with ERα-LBD and DNA (ΔG = −4.28 and −5.68 kcal/mol, respectively), while quantum chemical analyses indicated electron-accepting properties and a narrow HOMO–LUMO gap, suggesting efficient macromolecular interactions and intracellular ROS generation. Together, these findings demonstrate that the presence of a nucleus shifts the primary target of nanoparticle toxicity from membrane to genome, providing novel mechanistic insights. This comparative study offers a robust framework for understanding nanomaterial reactivity across taxa and informs One Health-oriented risk assessments. Full article

This study employed deep eutectic solvents (DES) combined with ultrasonic-assisted extraction technology to green and efficiently extract flavonoids from honeysuckle, and systematically evaluated its inhibitory mechanism on α-amylase (α-AMY). Through comparative screening of six DES systems and traditional solvents, DES-4 (Choline chloride–propylene glycol) was identified as the optimal extraction solvent. After single-factor and response surface optimization, the yield of honeysuckle flavonoids (HF) was significantly increased to 9.12 ± 0.08% under the conditions of ultrasonic power 300 W, solid–liquid ratio 1:32 (g/mL), and extraction time 60 min. HPLC-MS analysis revealed that luteolin (4.59 ± 0.09 mg/g) and quercetin (3.05 ± 0.02 mg/g) were the main active components, and they exhibited strong antioxidant activity. Enzyme kinetics and Lineweaver–Burk analysis indicated that the inhibition type of HF on α-AMY was reversible mixed inhibition. Fluorescence spectroscopy, thermodynamic analysis, and molecular docking results further revealed that HF primarily bound to α-AMY through hydrogen bonds and van der Waals forces (ΔH = −63.80 kJ/mol, ΔS = −0.19 J/mol·K), causing static fluorescence quenching and altering its hydrophobic microenvironment and spatial conformation. This study aims to provide new theoretical basis for the green and efficient extraction of HF and its development and application in functional foods and natural medicines. Full article

Quantum computers, due to their superposition and entanglement properties, provide significant advantages in solving certain problems compared with classical computers. Therefore, it is crucial to identify issues that can be efficiently solved by noisy intermediate-scale quantum (NISQ) systems. Xanadu has introduced the X8 quantum chip, based on integrated photonic technology, along with important photonic platforms such as Strawberry Fields and Gaussian Boson Sampling (GBS), to solve specific computational problems. In this review article, after reviewing Boson Sampling (BS) and Gaussian Boson Sampling (GBS), we discuss the relationship between GBS and graph theory, including how graphs can be encoded in GBS. Some applications of GBS, particularly molecular docking and molecular vibrations, are also considered. The future goal of this study is to identify problems that can be represented as small graphs and solved using GBS with a limited number of optical modes. Full article

CRISPR-Cas systems have transformed genome engineering with their exceptional precision, programmability, and affordability. Although they originate from microbial defense mechanisms, expanding their use, especially in therapeutics, requires a chemically oriented framework that allows for tunable, reversible, and safe gene editing. This review offers a multidisciplinary look at recent progress in the structural, synthetic, and computational aspects of CRISPR-Cas technologies. Structural analyses examine the domain architectures of Cas enzymes, including the recognition (REC), nuclease (HNH and RuvC), and PAM-interacting domains, emphasizing the catalytic importance of divalent metal ions. Comparative insights into Cas9, Cas12, and Cas13 demonstrate functional diversity across DNA- and RNA-targeting systems, supported by high-resolution structural data on guide RNA pairing and conformational dynamics. The review highlights advances in chemical modulation, such as anti-CRISPR proteins, small-molecule inhibitors, and stimuli-responsive switches, focusing on structure–activity relationships. Additionally, bioorganic delivery systems like lipid nanoparticles, polymers, and cell-penetrating peptides are discussed for their role in improving in vivo delivery through formulation chemistry. Computational chemistry methods—molecular docking, molecular dynamics simulations, and virtual screening—are identified as critical tools for discovering and optimizing modulators. The use of AI-driven tools is proposed as a promising direction for rational CRISPR design. Overall, this chemistry-focused perspective emphasizes the importance of molecular control in developing the next generation of programmable and safe CRISPR-based therapies. Full article

This study integrates network toxicology with molecular docking technology to systematically elucidate the key molecular mechanisms and signaling pathways by which bisphenol A (BPA) induces obesity. By cross-referencing multiple databases—including the Comparative Toxicogenomics Database (CTD), SwissTarget prediction platform, and PharmMapper—potential BPA target genes were identified, yielding a total of 1326 candidate targets. Obesity-related genes were collected from GeneCards and OMIM databases, yielding 4570 disease-associated targets. Among these, 653 overlapping genes were identified as potential mediators linking BPA exposure to obesity. Protein interaction networks were constructed using STRING and Cytoscape, and the MCC algorithm identified five core hub genes: STAT3, MYC, TP53, IL6, and mTOR. Validation using random datasets demonstrated significant upregulation of these genes in the obesity group (p < 0.05), highlighting their potential central role in BPA-induced obesity effects. Functional enrichment analysis via GO and KEGG pathways indicated that BPA may promote obesity by interfering with endocrine signaling, activating lipid metabolism, and stimulating atherosclerosis pathways. Molecular docking analysis using CB-Dock2 confirmed strong binding affinity between BPA and core targets, providing structural evidence for their potential interactions. This study elucidates the potential biological mechanism by which BPA exacerbates obesity through endocrine disruption and metabolic reprogramming, employing a multidimensional approach encompassing cross-target analysis, pathway enrichment, and molecular interactions. It provides an innovative systems toxicology framework and empirical basis for assessing metabolic health risks induced by environmental pollutants. Full article

Insecticide resistance has become a critical issue threatening global agricultural production and food security. Previous studies have primarily focused on resistance mechanisms such as target-site mutations, enhanced metabolic detoxification, and reduced cuticular penetration. However, growing evidence in recent years indicates that odorant-binding proteins (OBPs) and chemosensory proteins (CSPs)—beyond their roles in chemoreception—also play key roles in the development of insecticide resistance. Research has revealed that these proteins significantly modulate insect susceptibility to insecticides through various mechanisms, including direct binding to insecticides, regulation of detoxification metabolic pathways, and influence on behavioral adaptations in pests. This review also systematically summarizes modern research strategies employed to investigate OBPs/CSPs functions, including high-throughput omics technologies, RNA interference, CRISPR-Cas9 gene editing, and molecular docking, while discussing the potential of targeting these proteins for developing novel insecticides and resistance management strategies. Although significant progress has been made in laboratory studies, the practical application of OBPs/CSPs-mediated resistance mechanisms still faces multiple challenges. Future research should prioritize multi-gene targeting strategies, cross-species functional validation, and field trial implementation to facilitate the development of green and precise pest control approaches based on OBPs and CSPs, thereby offering new pathways for sustainable agriculture. Full article

Background/Objectives: Thyroid cancer (TC) is the most common type of endocrine neoplasm and is increasing in incidence, particularly papillary thyroid carcinoma (PTC). Early-stage disease has a favorable prognosis; however, advanced forms, such as anaplastic thyroid carcinoma, complicate treatment. Long non-coding RNAs (lncRNAs), longer than 200 nucleotides and non-coding, together with microRNAs, have emerged as major regulators of TC pathogenesis. This review summarizes data on how dysregulated lncRNAs influence the hallmarks of cancer in thyroid malignancies. Methods: We reviewed the literature on the role of lncRNAs and microRNAs in TC, focusing on their functions as competing endogenous RNAs (ceRNAs), regulators of PI3K/AKT and Wnt/β-catenin pathways, and controllers of epigenetic alterations. Results: Dysregulated lncRNAs contribute to hallmarks including sustained growth, evading suppressors, resisting death, replicative immortality, angiogenesis, invasion, metabolic reprogramming, immune evasion, genomic instability, and tumor-promoting inflammation. ceRNA mechanisms amplify immune evasion by regulating checkpoint proteins and cytokines, altering immune cell activity. Altered lncRNA profiles correlate with aggressiveness, metastasis, and prognosis. Notable lncRNAs, such as H19, MALAT1, and DOCK9-AS2, dysregulate oncogenic pathways and represent potential biomarkers. Conclusions: Advances in therapeutics suggest inhibiting oncogenic lncRNAs or restoring tumor-suppressive lncRNAs via RNA interference, antisense oligonucleotides, or CRISPR/Cas9 editing. New technologies, including single-cell RNA sequencing and spatial transcriptomics, will improve understanding of heterogeneous lncRNA–microRNA networks in TC and support precision medicine. LncRNAs signify both molecular drivers and clinical targets for thyroid cancer. Full article

Molecular docking has emerged as a pivotal computational approach in agri-food research, offering a rapid and targeted means to discover bioactive molecules for crop protection and food safety. Its ability to predict and visualize interactions between natural or synthetic compounds and specific biological targets provides valuable opportunities to address urgent agricultural challenges, including climate change and the rise in resistant crop pathogens. By enabling the in silico screening of diverse chemical entities, this technique facilitates the identification of molecules with antimicrobial and antifungal properties, specifically designed to interact with critical enzymatic pathways in plant pathogens. Recent advancements, such as the integration of molecular dynamics simulations and artificial intelligence-enhanced scoring functions, have significantly improved docking accuracy by addressing limitations like protein flexibility and solvent effects. These technological improvements have accelerated the discovery of eco-friendly biopesticides and multifunctional nutraceutical agents. Promising developments include nanoparticle-based delivery systems that enhance the stability and efficacy of bioactive molecules. Despite its potential, molecular docking still faces challenges related to incomplete protein structures, variability in scoring algorithms, and limited experimental validation in agricultural contexts. This work highlights these limitations while outlining current trends and future prospects to guide its effective application in agri-food biotechnology. Full article

Ozonation is an emergent green technology that modifies the chemical composition and bioactivity of natural oils, creating new opportunities for functional and biomedical use. In this study, the chemical changes and in vitro activities of lettuce (Lactuca sativa) oil before and after ozonation were evaluated. Gas chromatography–mass spectrometry (GC–MS) revealed an increase in both the number and diversity of constituents in ozonated oil, with (Z)-13-docosenamide and trans-13-octadecenoic acid as predominant components. Fourier-transform infrared (FTIR) spectra showed overall similarity between native and ozonated oils, but with three additional characteristic bands in the ozonated sample. Bioassays demonstrated that ozonation enhanced anti-Helicobacter pylori activity (inhibition zone 21.3 ± 0.3 mm), supported bactericidal effects, and improved antibiofilm and antihemolytic properties. The antioxidant capacity of ozonated oil was modestly increased (IC₅₀ = 3.95 ± 0.4 µg/mL), while butyrylcholinesterase inhibition was more markedly enhanced (IC₅₀ = 2.58 ± 0.6 µg/mL), compared to that of the non-ozonated oil (IC₅₀ = 6.14 ± 0.3 µg/mL and IC₅₀ = 4.38 ± 0.4 µg/mL, respectively). Molecular docking suggested strong interactions of major ozonation-derived compounds with human BuChE and H. pylori urease, providing mechanistic support for the observed activities. Overall, these results indicate that ozonation modestly but consistently enhances the biological potential of lettuce oil through compositional shifts, highlighting its promise for development as a safe functional food ingredient with possible biomedical applications. Full article

Parkinson’s disease (PD) is a neurodegenerative disease that is closely related to genetic and environmental factors, among which pesticide exposure is considered an important risk factor. Fresh jujube and hawthorn, as widely consumed fruits, may contain pesticide residues, but the potential effects of long-term low-dose intake on PD are not yet clear. This study combines network toxicology and molecular docking technology to elucidate the molecular mechanism of PD induced by residual pesticides in fresh jujube and hawthorn. Firstly, common risk pesticides (such as organophosphates and pyrethroids) in fresh jujube and hawthorn were screened through the database. Subsequently, a “pesticide target—PD” interactive network was constructed using network toxicology to predict key targets and related pathways. Finally, molecular docking technology was used to verify the binding ability of pesticide molecules to PD-related proteins. The results indicate that some pesticides (such as chlorpyrifos and cypermethrin) may increase the risk of PD by affecting lipid metabolism and oxidative stress response. This study provides a new approach for assessing the neurotoxicity of pesticide residues and suggests the need to pay attention to the potential impact of dietary pesticide exposure on PD, providing a scientific basis for food safety regulation and PD prevention strategies. Full article

The main objective of the study was to choose the best salicylic acid-based monomers through in silico research to improve the antibacterial effects of dental prostheses, refine the synthesis process of such monomers, and examine their antibacterial and antifungal properties in vitro, forecast the long-term stability in an oral biological environment using molecular docking software and synthesizing new copolymers. Based on their strong antibacterial activity and low toxicity compared to other derivatives, the allyl ester of salicylic acid (AESA) and the allyl ester of acetylsalicylic acid (AEASA) were chosen as the study objects. Salicylic and acetylsalicylic acids were esterified with allyl alcohol and allyl bromide in a variety of solvents and temperatures to synthesize AESA and AEASA. The optimal conditions were identified with a yield of 78%. IR spectroscopy was used to confirm the chemical structure of synthesized molecules. In the presence of peroxybenzoyl, the regularities of the polymerization process between the obtained monomer and oligoethylene macromonomer (PEMM) were examined. To obtain new antibacterial oligomers containing a salicylic group and to study their physico-chemical properties, a technology for obtaining the copolymers of AESA with PEMM was developed, and their physical, mechanical, and antimicrobial properties were studied. Full article

Nelumbinis folium (N. folium) exhibits hypolipidemic effects and shows great potential for application in lipid-lowering drugs and healthcare products. This study aimed to investigate the mechanism underlying the hypolipidemic effects of the alkaloid fraction of N. folium (AFN). Animal experiments demonstrated that AFN significantly reduced blood lipid levels and ameliorated liver damage in hyperlipidemic mice. RNA-seq analysis identified 26 reverse-regulated differentially expressed genes (DEGs), which were primarily involved in the PPAR signaling pathway, fat digestion and absorption, and fatty acid degradation. Using UPLC-MSⁿ, 30 plasma-absorbed components were identified, including 13 prototype alkaloids. Among these, three key active components—nuciferine, N-nornuciferine, and N-methylisococlaurine—were screened via network topology analysis. Molecular docking revealed strong binding affinities between these compounds and key targets. The results showed that N-methylisococlaurine bound to SLC27A4 and CPT1A with strong affinity, while nuciferine and N-nornuciferine bound to ACADVL and PPARA. RT-qPCR results confirmed that AFN modulates the expression of FABP1, SLC27A4, PPARA, CPT1A, ACAA2, APOC3, and APOA4. These findings suggest that AFN exerts its hypolipidemic effects through multi-component, multi-target, and multi-pathway mechanisms. Full article