Search Results (28,808)

Ovarian function relies on a network of well-coordinated molecular mechanisms that regulate follicular development, oocyte maturation, ovulation, and corpus luteum function. When these processes are disrupted, infertility can result. Extracellular matrix (ECM) remodeling represents a central regulatory component in these processes and is essential for follicle rupture and oocyte release. This mechanism involves metalloproteinases (MMPs), mainly MMP-2 and MMP-9, which degrade the ECM and allow the necessary structural changes. Other ECM-modulating proteases, such as ADAM and ADAMTS families, also contribute to this process. Their activity is tightly regulated by tissue inhibitors of metalloproteinases (TIMPs), ensuring that tissue remodeling occurs in a controlled manner. Disruption of the balance between MMPs and TIMPs increases the risk of infertility-related conditions such as polycystic ovary syndrome (PCOS), endometriosis, luteinizing hormone (LH) deficiency syndrome, and ovarian aging. In addition to the ECM, other factors, including intracellular signaling pathways, oxidative stress (OS), and mitochondrial function, contribute to ovarian physiology and directly affect oocyte quality and viability. This narrative review focuses on the molecular mechanisms governing ovarian function, with particular emphasis on the remodeling of the ECM by MMPs during ovulation, and examines how their disorders contribute to infertility. A deeper understanding of these mechanisms may lead to the identification of new therapeutic targets and the improvement of assisted reproduction outcomes. Full article

Brain organoids represent three-dimensional structures that allow for human-specific studies in brain development, pathology and therapeutics. These self-organizing systems, formed through the differentiation of human pluripotent stem cells, can mimic important cellular and molecular events of brain development and therefore serve as a platform for the investigation of neurodevelopmental and neurodegenerative diseases, brain injuries, and tumorigenesis. Although brain organoids show promising perspectives in the study of human physiology, existing brain organoid platforms are hindered by issues of under vascularization, immaturity and protocol variability. Nevertheless, the rapid development of new bioengineering, microfluidic and multi-omics tools and approaches allows us to overcome existing problems and increase the physiological significance of these organoids. Brain organoid transplantation and functional studies further enhance the applications of brain organoids in drug screening, disease modeling and personalized medicine. Here, we provide an overview of recent developments in the field of brain organoid cultures, functional characteristics and translational applications. Full article

Overcoming the inherent permeability–selectivity trade−off is essential to broaden the practical application of polyamide (PA) reverse osmosis (RO) membranes in brackish water desalination. In this study, we developed a facile and cost-effective alkaline (NaOH) post-treatment method to fabricate high−performance loose-structured RO membranes. The NaOH post−treatment hydrolyzed part of the amide bonds within the membrane, converting them to negatively charged carboxyl groups. This process led to a slight increase in pore size and the formation of a looser structure. Molecular weight cut−off (MWCO) measurements confirmed that the pore size slightly increased from 0.19 nm to 0.21 nm, while X−ray photoelectron spectroscopy (XPS) and zeta potential measurements confirmed the conversion of amide bonds to carboxyl groups, which further enhanced the surface electronegativity. The synergistic effects of pore size enlargement and surface charge modification were elucidated as the key mechanisms for performance enhancement. The TPA membrane exhibited a 2−fold increase in water permeance (from 1.05 to 3.21 L m⁻² h⁻¹ bar⁻¹), while the enhanced surface negative charge contributed to maintaining a high NaCl rejection of 98.5%. Additionally, the membrane also exhibited excellent pH stability as well as long-term stability over 100 h of continuous operation. This easily scalable post−treatment strategy offers a low−cost route to fabricate loose-structured membranes, with significant potential to enhance efficiency and reduce costs in brackish water desalination. Full article

Ice adhesion on exposed structures remains a major operational challenge, motivating the search for passive, material-based anti-icing strategies. Molecular dynamics offers a controlled way to investigate ice–surface interactions beyond the limits of experimental setups. In this work, we develop a simulation framework to model the impact of solid hexagonal ice droplets on metallic substrates. Ice impacts are simulated across a range of velocities (10–120 m/s), temperatures (120–250 K), and face-centred cubic surface materials (gold, copper, silver, aluminum, and nickel). Using LAMMPS, mW water force-field, EAM/Alloy metal potentials, and Lennard-Jones water–surface interactions, we quantify phase evolution through angular order parameter and quasi-liquid layer measurements, complemented by the CHILL+ algorithm in OVITO. By isolating all external factors, we show that melting increases with velocity and temperature and correlates with substrate properties: metals with high thermal diffusivity and low Young’s modulus tend to decrease post-collision ice melting. The ratio of the former to the latter, a derived index of merit Υ, significantly correlates with melting percentage and identifies silver as the most effective anti-ice material examined. Statistical analyses strongly suggest that these surface properties influence interfacial melting, supporting the use of this modelling framework for screening and designing anti-icing materials. Full article

Oral infections caused by antibiotic-resistant bacteria represent an emerging biomedical hazard and growing challenge for modern dentistry. To address this issue, Ag– and Cu–ZnO nanocomposites (NCs) were synthesized using ZnO carrier to combat the oral pathogens Streptococcus mutans and Streptococcus sobrinus. A comprehensive analysis of chemically synthesized metal oxide nanocomposites (MONCs) was performed, combining physicochemical characterization (TEM, XRD, ζ-potential, DLS, pH, and PFO/PSO kinetic models) with biological toxicity assessment (MIC, ATR–FTIR, SEM, and FAMEs) to better understand their antimicrobial mechanisms. The results confirmed that the synthesized nanoproducts fulfill the criteria for nanomaterials (NMs) (particle size < 100 nm). Among them, Ag–ZnO exhibited the highest antibacterial activity against both strains (MIC = 50 mg L⁻¹). Kinetic modeling revealed faster and more efficient Ag ion release from Ag–ZnO NCs compared to Cu from Cu–ZnO NCs. Molecular analyses indicated strong MONC–bacterial interactions at the cell surface, leading to changes in protein secondary structures, alterations in lipid composition, and disruption of Gram-positive bacterial membranes. Additionally, Ag–ZnO inhibited chain and cluster formation in both bacterial species, while Cu–ZnO affected only S. sobrinus. Overall, Ag– and Cu–ZnO NCs show strong potential as antimicrobial agents against oral pathogens. Full article

In this paper, to remove the water lock effect in tight gas reservoirs, amphipathic polymer-modified titanium quantum dots (PTQs) were synthesized via in situ polymerization, showing a hyper-branched structure and an excellent synergistic effect with the nonionic fluorocarbon surfactant to break the water lock. The molecular structure, fluorescent property, and micromorphology of the PTQs were obtained. The surface activity and wettability alteration of rock are discussed. Results show that PTQs have zwitterionic hydrophilic groups and the hydrophobic structure of long-chain groups on their molecular structure. PTQ fluid, with a median particle size of 3.6 nm, showed strong green fluorescence and had excellent dispersibility in 50,000 mg/L of standard saline fluid at 120 °C. Additionally, the surface tension decreased to 18.6 mN/m at a PTQ concentration of 0.08%. At a 0.1% concentration, PTQ fluid altered the water wettability of tight sandstone to 67.2°, which resulted in lower capillary resistance. Furthermore, the surfactant (PHPE) had a good synergistic effect with the PTQs to decrease surface tension and alter the wettability of the sandstone surface, leading to lower surface tension and significant amphiphobicity. The strong surface activity of PTQs results from their specific molecular structure, which enables electrostatic attraction, quantum size effects, hydrogen bonding, and van der Waals forces between the inter-polar molecules of PTQs and the surface of sandstone to forcefully eliminate the water lock effect. This study offers key guidance for the development of a high-performance water-lock-breaking agent and application of titanium quantum dots in tight gas reservoirs. Full article

Aqueous redox flow batteries (ARFBs) are a promising solution for large-scale energy storage; however, the development of organic posolytes that combine high redox potential with long-term stability remains a significant hurdle. This study introduces sodium 3-(10H-phenoxazin-10-yl)propane-1-sulfonate (POZS), a novel sulfonate-functionalized phenoxazine derivative designed to overcome these limitations. By incorporating hydrophilic anionic sulfonic groups, this molecular engineering strategy enhances the structural stability of redox-active phenoxazine materials. Although POZS shows limited solubility in pure water, its solubility increases to 0.98 M (equivalent to a charge capacity of 26.3 Ah L⁻¹) upon the addition of 1.5 M tetraethylammonium chloride (TEAC). This enhancement suggests that the supporting electrolyte optimizes the ionic environment and mitigates intermolecular aggregation, thereby facilitating higher active species concentration. Electrochemical characterization of POZS reveals a highly positive redox potential of 1.51 V (vs. Zn/Zn²⁺) and rapid electron transfer kinetics (2.02 × 10⁻² cm s⁻¹). When tested in a zinc-based hybrid flow cell, the POZS posolyte demonstrates excellent rate capability (up to 50 mA cm⁻²) and a temporal capacity fade rate of 0.335% per hour over 500 cycles—a nearly five-fold improvement over previously reported quaternized phenoxazines. Post-cycling analyses indicate that while the phenoxazine core remains susceptible to nucleophilic ring substitution, the pendant sulfonate groups ensure that any resulting byproducts remain soluble, preventing the catastrophic depletion typically caused by the precipitation of degraded active species. These findings establish a robust molecular framework for the design of high-potential, durable organic posolytes for sustainable energy storage systems. Full article

The human genome produces a large repertoire of non-coding RNAs (ncRNAs) with important regulatory roles in development, physiology, and most of diseases. Among these, long non-coding RNAs (lncRNAs) have emerged as key modulators of gene expression, chromatin organization, and cellular homeostasis, despite displaying remarkably low primary-sequence conservation across species. This apparent evolutionary paradox questions the limitations of predicting biological function based on conservation, particularly across different biological domains. Here, we examine current evidence on lncRNA evolution, with a focus on their roles in metabolic regulation compared with neurobiological processes. We hypothesize that lncRNAs involved in ancient and conserved pathways such as metabolism may be under stronger evolutionary constraint than those associated with higher-order, species-specific traits, although available data support a more nuanced interpretation. Functional importance often correlates poorly with linear sequence conservation and instead appears to depend on higher-level features, including RNA secondary or tertiary structure, genomic context, regulatory architecture, and interactions with conserved molecular partners. We propose a systematic comparative framework to empirically assess conservation among metabolism- and neuro-associated lncRNAs using phylogenetic, syntenic, structural, and expression-based metrics. Finally, we discuss the therapeutic implications of lncRNA biology, highlighting how a deeper understanding of their evolutionary and mechanistic properties may inform the development of more precise and effective RNA-targeting strategies. Together, these insights underscore the non-coding transcriptome as a critical frontier for both fundamental biology and precision medicine. Full article

Preeclampsia (PE) is associated with systemic oxidative stress and vascular dysfunction, yet its effects on red blood cell (RBC) stability and mechanics remain incompletely understood. Here, we investigate the structural and nanomechanical alterations of RBCs in third-trimester pregnancies complicated by non-severe and severe PE, compared with normotensive controls. RBCs are analyzed using differential scanning calorimetry (DSC) to assess protein thermal stability and atomic force microscopy (AFM) to determine membrane elasticity (Young’s modulus) during in vitro aging. Linear mixed-effects models аre applied to evaluate the effects of disease severity, storage time, and their (group × storage time) interaction. DSC reveals that Band 3 and hemoglobin exhibited pronounced destabilization in PE, with severe cases showing earlier and larger reductions in transition temperatures and heat capacities, indicative of disrupted membrane–cytoskeletal interactions. AFM confirms that these molecular changes translate into functional consequences: control and non-severe PE RBCs show physiological softening over time, whereas severe PE RBCs undergo pathological stiffening. Statistical modeling demonstrates strong time, group, and interaction effects for both thermodynamic and mechanical parameters. Together, these findings identify the Band 3–hemoglobin macrocomplex as a primary target of PE-induced RBC alterations and suggest that combined thermodynamic–nanomechanical profiling can serve as a sensitive approach to detect early subclinical RBC damage not detectable by routine hematological tests. Full article

The crosslinked binders formed by using glycidyl azide polymer (GAP) as the binder matrix and bis-propargyl succinate (BPS) as the curing agent have good application prospects in the field of solid propellants. Aiming at the shortcomings of traditional experimental research, such as high cost, and molecular dynamics (MD) simulation, which are time-consuming for complex combination problems, this study will realize accurate prediction of the mechanical properties of binders through machine learning (ML) based on the molecular simulation dataset. Firstly, 273 sets of GAP-BPS binder models under different conditions were formed based on 21 crosslinking degrees and 13 temperatures, and MD simulation and mechanical property simulation were carried out. Then, the initial conditions of molecular simulation (crosslinking degree, temperature) and structural parameters (free volume) were taken as features, and the bulk modulus and shear modulus were taken as labels to form the dataset. Three machine learning models were trained and evaluated based on this dataset to test their prediction performance. Based on the cross-validation results, the Tabular Prior Data Fitting Network (TabPFN) exhibits the highest average prediction values (the average R² for bulk modulus and shear modulus were 0.9684 and 0.8827, respectively). But the significance analysis reveals that TabPFN significantly outperforms the RF model only in predicting bulk modulus. In subsequent prediction tasks with smaller datasets, TabPFN achieves superior average prediction values compared with RF and XGBoost. Full article

Background/Objectives: To address the limitations of natural curcumin, this study focuses on the functional evaluation of structurally optimized derivatives. We aimed to elucidate structure–activity relationships (SAR) and the stage-specific molecular mechanisms of adipogenesis inhibition using an in vitro cellular assay. Methods: Four novel curcuminoids were synthesized and evaluated in 3T3-L1 preadipocytes against natural curcumin (Curcuminoid I). Efficacy and mechanisms were assessed via cell viability assays, quantitative Oil Red O staining, and time-dependent transcriptional profiling (qPCR/Western blotting) of the KLF family and master regulators. Results: SAR analysis identified Curcuminoid III (symmetric 3,5-dimethoxy-4-hydroxy) as the most potent and safe candidate, whereas Curcuminoid IV exhibited cytotoxicity. Time-course analysis revealed a distinct step-wise inhibition mechanism wherein Curcuminoid III significantly upregulated the differentiation repressor KLF2 at the immediate-early phase. This rapid modulation effectively prevented the subsequent induction of pro-adipogenic factors, including KLF9, KLF15, PPARγ, and C/EBPα, in the mid-stage (3–5 d). Consequently, the expression of the maturation marker aP2 was robustly suppressed by the late stage (5–7 d). Conclusions: The symmetric 3,5-dimethoxy-4-hydroxy substitution pattern appears to confer strong anti-adipogenic activity to Curcuminoid III. Early modulation of the KLF2–PPARγ axis at the onset of differentiation may initiate a cascading inhibitory effect throughout the adipogenic program. These findings highlight the potential of structurally optimized plant-derived bioactive compounds as regulators of metabolic cell fate. Full article

Siponimod, a selective sphingosine 1-phosphate (S1P) receptor modulator, represents a next-generation therapeutic drug for active secondary progressive multiple sclerosis. This study conducted in-depth forced degradation studies of siponimod in solid state subjected to acidic, alkaline, oxidative, photolytic, and thermal conditions, in compliance with ICH guidelines Q1A (R2) and Q3A (R2). An HPLC method was developed to quantify siponimod and separate its degradation products (DPs). The DPs were characterized using LC-HRMS/MS and LC-MSⁿ techniques. Moreover, the toxicological profiles of siponimod and its DPs were evaluated through the in silico tools ProTox 3.0 and ADMETlab 3.0, with molecular docking and dynamics simulations assessing their binding to the S1P1 receptor. Siponimod was stable to light but degraded under acidic, alkaline, oxidative, and thermal stress, producing five products: DP-1 (acidic), DP-2/3 (oxidative), DP-4 (hydrolytic), and DP-5 (thermal). The toxicity prediction suggested that neither siponimod nor its DPs exhibited carcinogenic or mutagenic potential, and the molecular modeling analysis revealed that DP-2 and DP-3 demonstrated favorable binding affinities, with stable dynamic profiles and thermodynamic properties that closely resembled those of siponimod. As far as we know, this is the first study on the structural elucidation of the DPs of siponimod by LC-HRMS/MS and LC-MSⁿ. Full article

Autoimmune diseases arise from the failure of self-tolerance. The recognition of self-antigen peptide–MHC (pMHC) complexes by the T-cell receptor (TCR) is the fundamental event triggering autoimmune pathogenesis. While traditional immunosuppressants provide broad systemic effects, they often compromise global immunity. Emerging molecular strategies aim to selectively disrupt the trimolecular complex—comprising the TCR, the antigenic peptide, and the MHC molecule—to induce antigen-specific tolerance. This review highlights the pMHC–TCR interaction as the primary molecular checkpoint for antigen-specific intervention. We discuss the structural basis of these interactions and their potential to redefine the therapeutic landscape for autoimmune diseases (ADs). We examine the molecular drivers of tolerance breakdown—including genetic susceptibility, molecular mimicry, post-translational modifications (PTMs), and ectopic MHC II expression—that shape the autoreactive T-cell landscape. This review examines current advancements in biological and pharmacological interventions, such as pMHC-decorated nanoparticles and soluble pMHC, to reprogram pathogenic T-cell response. We also explored CAR-T therapy strategies for autoimmune diseases, such as CAR-Treg, designed to precisely modulate pMHC-TCR signaling. Collectively, these precision interventions in immunological synapse assembly during autoimmune response are considered the basis for safer, antigen-specific immunotherapy capable of restoring self-tolerance without global immunosuppression. Full article

In this research, PLA biocomposites reinforced with 20 wt% flax fibers modified with 1, 5, 10, and 20% concentrations of trans-cinnamic acid (TC) were prepared. The materials were systematically characterized to evaluate their structural, thermal, viscoelastic, surface, and functional properties. Thermal stability and phase transitions were analyzed using thermogravimetric analysis (TG) and differential scanning calorimetry (DSC), while viscoelastic behavior and molecular relaxation processes were investigated by dynamic mechanical analysis (DMA). To elucidate failure mechanisms and interfacial quality, fracture surface morphology after tensile testing was observed using scanning electron microscopy (SEM). Surface wettability was determined through water contact angle measurements, and antibacterial activity against Escherichia coli and Staphylococcus aureus was evaluated to assess the functional potential of the developed biocomposites. The results demonstrated that moderate fiber modification improved interfacial adhesion and enhanced thermo-mechanical performance. The highest contact angles were observed for 5% and 10% TC concentrations, indicating increased surface hydrophobicity, while strong antibacterial activity (R ≥ 6) was achieved for 10% and 20% TC. The research confirms that trans-cinnamic acid concentration governs multiple structure–property relationships, enabling controlled tuning of mechanical reinforcement and antibacterial functionality. Full article

Bovine spongiform encephalopathy (BSE) is a fatal transmissible spongiform encephalopathy caused by the misfolding of the host prion protein (PrP), representing a unique intersection between molecular pathology, neuroanatomy, and public health regulation. Although historically framed as a single feedborne epizootic, BSE is now recognized as a spectrum of strain-defined prion disorders encompassing classical and atypical forms with distinct origins, neuroanatomical trajectories, and surveillance implications. This review integrates advances in prion biology, neurodegenerative mechanisms, and anatomical pathways of neuroinvasion to reframe BSE as a heterogeneous disease entity. We synthesize evidence on PrP^C structure, trafficking, and proteolytic processing to explain how normal cellular physiology enables strain-specific conversion to pathogenic PrP^Sc and subsequent neurotoxicity. Distinct patterns of neuroinvasion and regional vulnerability are discussed for classical versus atypical (H- and L-type) BSE, highlighting differences in lymphoid involvement, brainstem targeting, and cortical or cerebellar tropism. We further examine how these biological differences translate into diagnostic sensitivity, surveillance design, and zoonotic risk assessment. By integrating molecular strain diversity with neuroanatomical connectivity, this review underscores the limitations of obex-centered surveillance for atypical BSE and emphasizes the need for proportionate yet precautionary monitoring strategies. These considerations should be interpreted in light of surveillance-dependent detection biases, which influence the apparent distribution of BSE forms. Ultimately, BSE emerges as a critical model for understanding how protein misfolding disorders bridge cellular mechanisms, animal health, and human public health policy. Full article