Search Results (14,517)

Age-related diseases such as cardiovascular disorders, neurodegeneration, and metabolic syndrome share a unifying pathological signature—persistent low-grade inflammation or “inflammaging”. Among the transcriptional regulators that orchestrate this process, RUNX1 has emerged as a pivotal molecular hub linking inflammation, cellular senescence, and tissue dysfunction. Traditionally recognized for its role in hematopoietic lineage specification, RUNX1 is now known to exert context-dependent regulatory functions across diverse organ systems. Its activation in aged tissues is driven by convergent pro-inflammatory and stress-related pathways—including NF-κB, MAPK, JAK/STAT, and oxidative signaling—that reinforce RUNX1 transcriptional activity through epigenetic reprogramming and chromatin remodeling. Sustained RUNX1 upregulation contributes to cellular senescence, fibrotic remodeling, and regenerative blockade, forming a self-perpetuating cycle of “inflammation amplification–functional decline”. In the cardiovascular, nervous, and hematopoietic systems, aberrant RUNX1 activation underlies fibrosis, neuroinflammation, and clonal hematopoiesis, respectively, establishing RUNX1 as a shared driver of age-associated pathology. The isoform-specific and temporally dynamic regulation of RUNX1 underpins its dual pro- and anti-inflammatory roles, highlighting its translational potential as both a biomarker and therapeutic target. A range of emerging intervention strategies has demonstrated promising capacity to precisely modulate RUNX1 activity. Collectively, these advances position RUNX1 at the intersection of inflammation, epigenetic instability, and tissue degeneration, opening new avenues for targeted intervention in inflammaging and age-related diseases. Full article

Turmeric (Curcuma longa L., Zingiberaceae) is a widely consumed spice and functional food valued for its bioactive constituents. Using an activity-guided strategy, this study identified the dichloromethane fraction as the most potent anti-inflammatory fraction, exhibiting markedly stronger inhibition of reactive oxygen species (ROS) production than ibuprofen (IC₅₀ $\le$ 0.4 vs. 11.2 μg/mL). Bioassay-guided purification yielded bisacurone (1), didemethoxycurcumin (2), and β-turmerone (3), with compounds 1 and 2 reported here for the first time in this fraction. Among them, β-turmerone displayed the strongest anti-inflammatory activity (IC₅₀ = 4.7 μg/mL), consistent with in silico docking and molecular dynamics analyses, revealing greater binding affinity and complex stability with myeloperoxidase (ΔG_bind = −20.90 vs. −18.89 kcal/mol for ibuprofen). Gas chromatography–mass spectrometry (GC-MS) profiling revealed a phytochemical profile dominated by turmerones and curlone, correlating with the observed bioactivity. None of the fractions exhibited acute toxicity in brine shrimp lethality assays, indicating a favorable preliminary safety profile. Our findings demonstrate the value of activity-guided isolation combined with computational validation for identifying turmeric-derived bioactives with promising nutraceutical potential, warranting further in vivo evaluation. Full article

Background: Curcuma bakerii is a species of the family Zingiberaceae, endemic to Bangladesh. This genus of rhizomatous plants is widely distributed in tropical regions worldwide and is valued for its medicinal, aromatic, and culinary properties. Methods: The complete chloroplast (cp) genome of C. bakerii was reconstructed using high-throughput sequencing data. Subsequently, the genome was functionally annotated, assembled, and analyzed to clarify its evolutionary dynamics and structural organization. Results: The study’s findings indicate that the genome size is 162,189 base pairs (bp) and that it has a normal quadripartite structure with a large single-copy (LSC) region also comprises a small single-copy (SSC) region and two inverted repeats (IRa and IRb). The GC content of the genome was 36.18%, consisting of 135 genes: 88 protein-coding, 39 tRNA, and 8 rRNA. The codon usage analysis revealed 22 high-frequency and five optimal codons indicative of codon bias. Analysis of repetitive sequences revealed 213 Simple Sequence Repeats (SSRs), most of which were A/T. Additionally, seven mutation hotspots were reported, with 68.08% of single-nucleotide polymorphisms (SNPs) detected in the coding region and 31.91% in the noncoding region. Nonsynonymous substitutions accounted for 63.78%, while synonymous substitutions accounted for 36.11%. Conclusions: Based on this study, cp genome sequencing is a useful tool for understanding the intrageneric relationships among Curcuma species. The research presents a complete cp genome of C. bakerii from Bangladesh and provides a useful genomic resource for the molecular evolution, phylogeny, and genetic diversity study of the genus Curcuma. Full article

Improving the wettability of coal dust with nonionic surfactants is crucial for mitigating environmental pollution. Here we compare two nonionic surfactants with distinct architectures—n-octyl-α-D-glucoside (OG) and Isooctyl glucoside (APG08)—to dissect how linear versus branched C8 chains govern the wetting of long-flame bituminous coal dust. Sedimentation and contact-angle measurements show that the linear OG, with reduced steric hindrance, assembles into a denser interfacial layer and delivers superior wetting. Corroborating spectroscopic and microscopic analyses (FTIR, XPS, and SEM) reveal that OG treatment increases hydroxyl functionalities and the O-element fraction at the coal surface; OG also drives stronger particle aggregation, consistent with markedly enhanced adsorption on coal. Molecular dynamics simulations further indicate tighter OG adsorption, a more homogeneous coal–water interfacial structure, and stronger binding of water to OG-modified surfaces. Collectively, these results identify chain linearity as a key design lever for nonionic glucosides and establish OG as a more effective wettability promoter for long-flame coal dust. Full article

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder in aged people with multifaceted molecular underpinnings. It poses a severe threat to millions of older adults worldwide. The understanding of the molecular mechanisms of PD development and the performance of its therapeutic strategies has not yet reached a satisfactory level. Methods: This study integrated six transcriptomic datasets to uncover key genes (KGs) and their underlying pathogenic mechanisms, providing insights into potential therapeutic strategies for PD. We designed a comprehensive computational pipeline using various bioinformatics tools and databases to investigate PD-causing KGs, focusing on their functions, pathways, regulatory mechanisms, and potential therapeutic drug molecules. Results: In order to explore PD-causing KGs, we initially identified 303 differentially expressed genes (DEGs) between PD and control samples with 204 upregulated and 99 downregulated DEGs using the LIMMA approach with threshold values at Adj. p-value < 0.05 and abs (log₂FC) ≥ 1.0. Then, protein–protein interaction (PPI) network analysis pinpointed seven top-ranked DEGs (GAPDH, PTEN, CCND1, APOE, ESR1, MAPK3/ERK1, and SNCA) as KGs or central modulators of PD pathogenesis. Regulatory network analysis of KGs identified 3 top-ranked transcription factors (FOXC1, NFKB1, and TFAP2A) and 6 microRNAs (hsa-let-7b-5p, hsa-mir-16-5p, and others) as the pivotal regulators of KGs. Gene Ontology (GO) terms and KEGG pathway enrichment analyses with KGs revealed several crucial biological processes, molecular functions, cellular components, and neurodegenerative pathways associated with the development of PD. Finally, the top five molecules guided by KGs (Nilotinib, Bromocriptine, Withaferin-A, Celastrol, and Donepezil) were identified as promising drug candidates against PD and validated computationally through ADME/T analysis and molecular dynamics simulation studies. Conclusions: The findings of this study may serve as valuable resources for developing effective treatment strategies for PD patients. Full article

Dynamic developmental states of follicles are regarded to be determinants of sexual maturation in fish ovaries. However, it is still a challenge to identify the critical points at which the developmental processes of different types of follicles interact and affect the ovarian development. In this study, four subtypes of the primary follicle (PF) in the ovarian folliculogenesis of zebrafish, i.e., the so-called PF-i, PF-ii, PF-iii, and PF-iv, are first identified by discontinuous NaCl-Percoll gradient centrifugation, as well as their respective morphological features. Then, for the four subtypes of PFs, stage-specific comparative analysis is employed to identify the differentially expressed genes and the differentially methylated regions, which have been validated to be significantly enriched in biological processes encompassing ribosomal biogenesis, meiotic progression, transcriptional regulation, and mitochondrial respiration. Results from transcriptional analysis further demonstrate significant changes in the expression profiles at different developmental stages from the PF-ii to the PF-iii. By molecular biology identification, it is shown that the enhancement of Notch and mTOR pathways can significantly regulate the ovarian development through the pacing effect of primary follicles. Clearly, all these uncovered results could provide a deeper understanding of the initial regulation of ovarian maturation, as well as a new multidisciplinary analytic tool to study follicle candidate regulators in the developmental process of other fish. Full article

Translating the exceptional luminescent properties of AIEgens into efficient and practical sensing devices has long been a major challenge restricting their practical application. In this work, we demonstrate a novel strategy based on phase separation to fabricate stable, high-surface-area sensing films that address the fluorescence quenching typically associated with conventional nanospheres. Fluorescent polysiloxanes bearing tetraphenylphenyl (TPP) side groups were synthesized and processed into fibrous films via electrospinning. Leveraging the intrinsic incompatibility of the polymer, entropy-driven phase separation generated an “sea–island” morphology. This hierarchical structure significantly enlarged the specific surface area and facilitated analyte diffusion, thereby improving the accessibility of active sites. Molecular dynamics simulations not only predicted the formation of this architecture but also clarified the underlying entropy-driven mechanism. Overall, this work provides a solid foundation and conceptual framework for investigating how quantitative regulation of lumogenic unit density and spatial distribution governs sensing performance. Full article

Protein–ligand complexes in crystal structures are well described by an array of bonding interactions among precisely defined functional groups. The present work examines how one representative complex behaves in one-microsecond molecular dynamics simulations, starting from a crystal structure with a native biological ligand bound, and proceeding to simulations of structures derived by docking of that native ligand, and then to docking of selected ligand analogs. The MD behaviors and system energies calculated in RMSD plateau regions using MM/GBSA are similar when initiated from the crystal structure or the structure with the docked native ligand, although independent replicate simulations differ. Despite these similarities, interatomic contact frequencies indicate that some contacts observed in the crystal structure are rarely sampled again; others are sampled only intermittently; and new contacts are recruited that can be more persistent. Docked structures of non-native ligand analogs were chosen for simulation by screening manually for features consistent with known binding interactions, and these displayed behaviors similar to those for the native ligand and, in some cases, similar calculated energies. Overall, ligands appear to cooperate dynamically with the protein in forming the observed interactions. Full article

SARS-CoV-2, the virus responsible for COVID-19, disrupts human cellular pathways through complex protein–protein interaction, contributing to disease progression. As the virus has evolved, emerging variants have exhibited differences in transmissibility, immune evasion, and pathogenicity, underscoring the need to investigate their distinct molecular interactions with host proteins. In this study, we constructed a comprehensive SARS–CoV–2–human protein–protein interaction network and analyzed the temporal evolution of pathway perturbations across different variants. We employed computational approaches, including network-based clustering and functional enrichment analysis, using our custom-developed Python (v3.13) pipeline, BioEnrichPy, to identify key host pathways perturbed by each SARS-CoV-2 variant. Our analyses revealed that while the early variants predominantly targeted respiratory and inflammatory pathways, later variants such as Delta and Omicron exerted more extensive systemic effects, notably impacting neurological and cardiovascular systems. Comparative analyses uncovered distinct, variant-specific molecular adaptations, underscoring the dynamic and evolving nature of SARS-CoV-2–host interactions. Furthermore, we identified host proteins and pathways that represent potential therapeutic vulnerabilities, which appear to have co-evolved with viral mutations. Full article

Smart nucleic acid hydrogels (SNAHs), endowed with stimulus responsiveness, function as programmable molecular switches that can perceive diverse external stimuli and undergo rapid, reversible, and highly specific conformational or performance changes. These dynamic properties have enabled the rational design of biosensors with bionic behaviors, facilitating cascaded “recognition–decision–execution” processes that support advanced biological analysis. Consequently, SNAHs are recognized as a core breakthrough for the next generation of intelligent biosensing units. However, a systematic mapping between SNAH design strategies, specific stimuli, and application fields remains lacking. This review mainly analyzes advances in SNAH-based biosensors over the past five years, proposing flexible and feasible design strategies and key trends in customization. Firstly, we systematically summarize molecular recognition modules involved in the construction of SNAHs, including aptamers, DNAzymes, antibodies, and specific binding peptides. Subsequently, we elaborate on the responses of these modules to external stimuli, so as to further facilitate the signal transduction of signals derived from physical, chemical, and biological sources involving temperature, light, magnetic fields, pH, nucleic acids, proteins, other biomolecules, and pathogens. Additionally, the review outlines the research progress of SNAHs in environmental monitoring, food safety, and medical diagnostics. Finally, we provide an integrated perspective on future opportunities and challenges, highlighting the innovative framework for designing SNAH-based biosensors and offering a practical roadmap for next-generation intelligent sensing applications. Full article

Proteins play an important role in living organisms, and, for most of them, the function depends on their structure. There are some proteins that have similar properties but different structures. An example of this is ice-binding proteins (IBPs), which have different structures but share the ability to bind to ice. Many organisms have evolved such proteins to help them survive in cold environments. Therefore, it is important to study the oligomeric state of the active form in solutions. The activity of IBP is related to the area of their ice-binding site. We have demonstrated the presence of oligomeric forms of protein in solution using multiple techniques, such as mass spectrometry, native gel electrophoresis, atomic force microscopy (AFM), isothermal titration calorimetry (ITC) and small-angle X-ray scattering (SAXS). It is noteworthy that, to date, there have been no reports of the oligomerization of ice-binding protein from Longhorn sculpin. Additionally, our findings suggest that larger molecules may influence the ability of proteins to bind to ice. In our study, the ice-binding protein forms elongated assemblies with limited intermonomer interfaces. The combination of SAXS and AFM data indicates a structure that combines compactness and flexibility and probably consists of four monomeric units. The employment of molecular modelling methodologies resulted in the attainment of a tetrameric complex that is in alignment with AFM data. Details of oligomers observed using the methods in our study emphasize the importance of different techniques that complement each other in resolving structural features. Additionally, we suggest that the protein particles, which were dispersed on the surface, exhibit softness or the form planar complexes with loose quaternary structures. It is conceivable that, depending on ionic strength and/or temperature, the various oligomeric forms of the ice-binding protein form thermodynamically more favorable complexes than their monomeric forms. Full article

Biodegradable microplastics can adsorb organic pollutants in aquatic environments, worsening contamination. However, the molecular mechanisms behind this association remain poorly understood. This study employs molecular dynamics (MD) simulations and density functional theory (DFT) calculations to systematically explore the molecular interactions between polylactic acid (PLA) and the herbicide acetochlor (ACT) in freshwater and a seawater analog. Our simulations reveal that PLA demonstrates a notably higher adsorption capacity for organic pollutants in seawater than in pure water. This improvement stems from three main factors: (i) PLA forms a more compact microstructure under saline conditions, (ii) its specific surface area increases, offering more active adsorption sites, and (iii) surface adsorption between PLA and ACT molecules dominates. DFT calculations support the MD simulation findings, demonstrating stronger PLA–ACT interaction energies in seawater. The adsorption process is mainly driven by two fundamental mechanisms: van der Waals forces and hydrogen bonding. Importantly, dissolved salt ions in seawater act as molecular bridges, facilitating interactions between PLA and ACT. Based on these insights, the study proposes conservative, testable risk indicators and planning/management implications for coastal drainage infrastructure, contributing to broader sustainable development objectives. Full article

We present a comprehensive computational study of the UV-visible absorption spectra of 7-methoxycoumarin and Nile red in aqueous solution. Our fully atomistic workflow couples classical molecular dynamics (MD) with polarizable QM/MM based on fluctuating charges (QM/FQ) and dipoles (QM/FQF$\mu$). Ensemble-averaged spectra are constructed from the snapshots extracted from the MD, embedding solvent fluctuations and specific solute–solvent interactions in the electronic response of organic dyes. The spectral profiles, obtained at the various levels, reflect the underlying solute–solvent interactions and dynamics, and we rationalize them in terms of hydrogen bonding and frontier molecular orbitals involved in the main electronic transitions. Finally, the simulated spectra and solvatochromic shifts are compared with the available experimental data, showing an overall good agreement and demonstrating the robustness of the computational protocol. Full article

Natural Product Synthesis (NPS) is a cornerstone of organic chemistry, historically rooted in the dual goals of structure elucidation and synthetic strategy development for bioactive compounds. Initially focused on identifying the structures of medicinally relevant natural products, NPS has evolved into a dynamic field with applications in drug discovery, immunotherapy, and smart materials. This evolution has been propelled by advances in reaction design, mechanistic insight, and the integration of green chemistry principles. A particularly promising development in NPS is the use of photochemistry, which harnesses light—a renewable energy source—to drive chemical transformations. Photochemical reactions offer unique excited-state reactivity, enabling synthetic pathways that are often inaccessible through thermal methods. Their precision and sustainability make them ideal for modern synthetic challenges. This review explores a wide range of photochemical reactions, from classical to contemporary, emphasizing their role in total synthesis. By showcasing their potential, the review aims to encourage broader adoption of photochemical strategies in the synthesis of complex natural products, promoting innovation at the intersection of molecular complexity, sustainability, and synthetic efficiency. Full article

Background/Objectives: Monkeypox is endemic to the African continent and has recently garnered global attention due to reported outbreaks in non-endemic nations. No approved drug is available for non-severe cases, and some isolates gained resistance to approved antivirals. In this study, we employed a drug repositioning strategy to evaluate the efficacy of existing FDA-approved antiviral drugs if repurposed for use against emerging Monkeypox, representing a cost-effective method for identifying novel therapeutic interventions. Methods: Methodology including Egyptian virus strain isolation, propagation and titration followed by in vitro studies, molecular docking and molecular dynamics simulations combined with binding free energy were carried out. Twenty-three FDA-approved drugs, including Abacavir, Acyclovir, Amantadine, Chloroquine, Daclatasvir, Dolutegravir, Entecavir, Favipiravir, Hydroxychloroquine, Lamivudine, Molnupiravir, Nevirapine, Oseltamivir, Penciclovir, Remdesivir, Ribavirin, Sofosbuvir, Tenofovir, Valaciclovir, Valganciclovir, Velpatasvir, Zanamivir, and Zidovudine, were screened for potential anti-monkeypox activity in vitro. In silico studies were carried out against three monkeypox proteins, Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13, to identify their potential targets. Results: In vitro testing showed that two antiviral drugs are positive. The employed computational methods indicate that remdesivir demonstrated superior binding patterns with elevated scores and stable complexes throughout the simulation. Conclusions: Our findings showed that Remdesivir therapeutic compound is potent against the tested strain of MPXV, and exhibited a robust binding affinity for Thymidylate Kinase, A42R Profilin-Like Protein, and VACV D13 enzymes, and thus may potentially be utilized as antiviral for the treatment of monkeypox virus. Full article