Search Results (2,055)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by Aβ accumulation, tau pathology, and associated oxidative and inflammatory changes, including matrix metalloproteinase (MMP) involvement. This study investigated plasma markers of oxidative damage, carbonyl stress, antioxidant status, and activities of MMP-9 and MMP-2 in AD patients and controls. Spectrophotometric and fluorescent assays were used to assess oxidative and carbonyl stress markers, while MMP activities were measured by gelatin zymography. AD patients exhibited significantly increased protein oxidation, carbonyl stress, and GSH/GSSG ratio, along with reduced total antioxidant capacity and superoxide dismutase activity. Plasma MMP-2 activity was elevated in AD patients, whereas MMP-9 activity showed no significant difference. Notable sex-specific patterns were observed: MMP-2 activity was higher in women with AD than in control women, while MMP-9 activity was increased in men with AD compared with control men. Fructosamine levels were elevated in men regardless of AD status and in AD women versus control women. APOE ε4 status had no significant effect on oxidative stress markers or MMP-9 activity, though higher MMP-2 activity in non-carriers with AD suggests its potential protective role. These findings support the relevance of peripheral biomarkers in AD and indicate sex-dependent pathways that may guide personalized therapeutic strategies. Full article

Glauber’s salt is a promising phase change material for thermal energy storage due to its high latent heat capacity of 234 J/g and melting point of 34 °C, making it well-suited for low-temperature heating applications. However, its practical use has been limited by phase separation and associated loss of performance during repeated thermal cycling. This study aimed to address this limitation through a novel stabilisation approach. The material was encapsulated within an emulsion matrix designed to physically constrain the salt and inhibit separation during melting and to form a phase change dispersion. The phase change dispersion was subjected to 100 controlled heating–cooling cycles whilst monitoring the latent heat capacity and phase transition plateaus. The phase change dispersion retained its thermal properties throughout testing, showing no measurable degradation in storage capacity nor shift in phase transition temperature. These results demonstrate that this encapsulation mechanism can effectively maintain the functional performance of Glauber’s salt under repeated thermal cycling. This approach may form the basis for more durable salt hydrate-based storage media and has potential relevance for applications in building heating, waste heat recovery and renewable energy integration. By improving stability, this method helps unlock the long-term operational viability of phase change materials. Full article

As an indigenous goat breed unique to southern China, Leizhou Black Goats (LZBGs) are highly valued for their rapid growth, high reproductive performance, and superior meat quality. However, their offspring frequently exhibit symptoms of muscle atrophy and malnutrition, suggesting potential genetic defects underlying these adverse phenotypes. As a unique extracellular matrix component, collagen Q (COLQ) is specifically enriched within the synaptic basal lamina at vertebrate neuromuscular junctions (NMJs), where it anchors acetylcholinesterase (AChE) to facilitate efficient acetylcholine hydrolysis, ensuring precise neuromuscular signaling. The current investigation sought to characterize the spectrum of genetic polymorphisms within the COLQ gene and assess their correlation with key production traits, including growth performance and meat quality parameters, in the LZBG population. Previously, through whole-genome sequencing and transcriptome sequencing analyses of an LZBG population, we identified four SNPs in the COLQ gene, namely, two missense mutations (SNP1: p.238A/S and SNP3: p.47G/S), one intronic variant (SNP2), and one synonymous mutation (SNP4: p.101P/P). Population genetic analysis revealed strong linkage disequilibrium between SNP1 and SNP2. Computational modeling of protein structures predicted that the identified missense mutations may lead to alterations in protein conformation. Association analyses demonstrated significant correlations of SNP1 and SNP3 with growth and meat quality traits (p < 0.05), where SNP3 reduced COLQ expression by 0.64-fold in homozygotes. Association analysis revealed that both SNP1 and SNP3 showed significant correlations with growth and meat quality traits in LZBGs (p < 0.05). Notably, SNP3 (p.47G/S) was found to regulate COLQ gene expression, reducing its levels by 0.64-fold in homozygous individuals, suggesting its potential as a genetic marker for selecting goats with superior growth performance and muscular development characteristics. The identified genetic variants establish a foundation for marker-assisted selection in LZBG breeding programs with particular relevance to growth performance enhancement, while also advancing the understanding of COLQ’s functional mechanisms in muscle development. Full article

Arabinogalactan proteins (AGPs) and extensins influence cell wall assembly and regulate plant cell mechanical properties through interactions with extracellular matrix polymers. These proteins may play a key role in the biochemical events underlying postharvest treatments aimed at controlling fruit texture and turgor loss associated with senescence-related disorders. We studied the temporal and spatial accumulation patterns of extensin and AGP isoforms constitutively expressed along with the profiling of nucleotide sugars UDP-galactose, UDP-arabinose, UDP-glucuronic acid, and UDP-rhamnose in Mara des Bois strawberries under different storage conditions. We also assessed the expression timing of AGP-encoding genes (FvAFP4, FvAGP5) and genes involved in key steps of post-translational glycosylation (FvP4H1, FvGAT20, FvGAT7). Whereas extensins are down-regulated, AGPs are transcriptionally regulated by cold and cold-high CO₂ and post-translationally modulated after transfer to 20 °C. Based on their subcellular localization, molecular properties, isoform-specific glycosylation, UDP-sugar availability, and timing-regulated expression, AGPs are likely involved in cell wall assembly and modulation of mechanical properties. Consequently, they may influence fruit texture and enhanced softening resistance, potentially counteracting senescence-associated disorders through CO₂-responsive signaling mechanisms. Conversely, the decrease in both UDP-galactose levels and AGPs gene expression in non-cold-stored senescent strawberries at 20 °C further supports their relevance in AGPs biosynthesis regulation and underscores their potential as markers for improving postharvest storage strategies. Full article

Breast cancer is the most prevalent solid tumor diagnosed in women worldwide, remaining a leading cause of cancer-related mortality. Among its subtypes, triple-negative breast cancer (TNBC) is characterized by high aggressiveness and heterogeneity, accounting for approximately 90% of breast cancer-related deaths. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR) and the insulin-like growth factor I receptor (IGF-IR), are critical cell growth and survival regulators, with their dysregulation closely related to therapy resistance in breast cancer. Studies on RTK targeting have shown promise, and recently attention has shifted toward developing more physiologically relevant preclinical models. Unlike traditional two-dimensional (2D) cell cultures, 3D models such as spheroids better mimic the complex nature of the tumor microenvironment (TME), offering a more accurate representation of tumor behavior and progression. This study utilized both 2D and 3D culture models to assess the effects of EGFR and IGF-IR inhibition, individually and in combination, in two TNBC cell lines with distinct metastatic potential. The results demonstrate that both receptors play critical roles in regulating key cellular functions, including migration, expression of epithelial-to-mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs). The use of 3D spheroid models enabled the evaluation of additional functional properties, such as spheroid growth and dissemination, revealing treatment-dependent responses to combined receptor inhibition. Overall, this dual-model approach underscores the importance of incorporating 3D culture systems in preclinical cancer research and provides new insights into the regulatory roles of EGFR and IGF-IR in TNBC progression. Full article

Background/Objectives: Cofilin, a key regulator of actin cytoskeleton dynamics, contributes to neuroinflammation, synaptic damage, and blood–brain barrier disruption in ischemic stroke. Despite its established role in stroke pathology, cofilin remains largely untargeted by existing therapeutics. This study aimed to identify potential cofilin-binding molecules by repurposing LIMK1 inhibitors through an integrated computational strategy. Methods: A cheminformatics pipeline combined QSAR modeling with four molecular fingerprint sets and multiple machine learning algorithms. The best-performing QSAR model (substructure–Random Forest) achieved R²_train = 0.8747 and R²_test = 0.8078, supporting the reliability of compound prioritization. Feature importance was assessed through SHAP analysis. Top candidates were subjected to molecular docking against cofilin, followed by 300 ns molecular dynamics simulations, MM-GBSA binding energy calculations, principal component analysis (PCA), and dynamic cross-correlation matrix (DCCM) analyses. Network pharmacology identified overlapping targets between selected compounds and stroke-related genes. Results: Three compounds, CHEMBL3613624, ZINC000653853876, and Gandotinib, were prioritized based on QSAR performance, binding affinity (−6.68, −6.25, and −5.61 Kcal/mol, respectively), and structural relevance. Docking studies confirmed key interactions with Asp98 and His133 on cofilin. Molecular dynamics simulations supported the stability of these interactions, with Gandotinib showing the highest conformational stability, and ZINC000653853876 exhibiting the most favorable energetic profile. Network pharmacology analysis revealed eight intersecting targets, including MAPK1, PRKCB, HDAC1, and serotonin receptors, associated with neuroinflammatory and vascular pathways in strokes. Conclusions: This study presents a rational, integrative repurposing framework for identifying cofilin-targeting compounds with potential therapeutic relevance in ischemic stroke. The selected candidates warrant further experimental validation. Full article

The rapid increase in electronic waste poses a significant environmental issue, with copper-rich residues considered among the most valuable fractions. Extracting copper of high purity from these materials is critical for advancing sustainable resource utilization. In this work, an oxidative refining approach employing a FeO–CaO–SiO₂ slag matrix was investigated to purify copper-bearing sludge. The method facilitated stable slag generation and ensured distinct separation between the metallic phase and slag. Although Fe and Si were removed effectively at relatively low processing temperatures, complete removal of Sn and S occurred only at 1300 °C, with traces of copper oxides persisting in the refined alloy. Overall, the findings suggest that the proposed slag system offers a reliable strategy for producing high-purity copper from secondary sources, underscoring its relevance in sustainable recycling of copper-enriched wastes. Full article

Achieving precise drug release in the colon remains a key objective in therapies for inflammatory bowel disease (IBD). Natural polysaccharides, including high-amylose starch (HAS) and pectin, offer relevant characteristics for localized drug delivery due to their biocompatibility, biodegradability, and adaptability. In this work, high-esterified pectin (HEP) was incorporated during the retrogradation of HAS to further form cohesive films without the need for organic solvents or high temperatures. The resulting matrices showed improved mucoadhesive performance, particularly under colonic conditions, where hydrophobic ester groups in HEP enhanced tissue adherence. This feature is critical for prolonged residence time in inflamed mucosa. Variations in HEP content directly influenced matrix density, fluid interaction, and mechanical resistance, without compromising film integrity. The high degree of esterification limited pH-dependent swelling and promoted alternative release mechanisms potentially related to enzymatic degradation. Such behavior contrasts with traditional low-esterified pectin (LEP) systems, suggesting that HEP may act as a structural modifier rather than a neutral excipient. Despite its widespread use in food systems, HEP remains underexplored in pharmaceutical matrices, especially in combination with retrograded starch (RS). The physicochemical and biointerfacial properties observed here underscore their applicability for the rational design of colonic delivery systems and provide a foundation for formulation strategies tailored to chronic intestinal disorders. Full article

Hamamelis virginiana (witch hazel) is traditionally used in dermatology for its antibacterial and anti-inflammatory effects. However, the number of studies on its chemical composition and potentials in skin protection remains limited. This study aimed to investigate the qualitative and quantitative composition of polyphenolic compounds in the leaves and bark of the plant, as well as to explore their antioxidant, anti-inflammatory, and extracellular matrix (ECM)-protective activities in skin-relevant cell models. Human dermal fibroblasts and keratinocytes were exposed to oxidative and inflammatory stimuli and pretreated with leaf and bark extracts. ROS levels, antioxidant enzyme activity (SOD, GPx, CAT), pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), and inhibition of collagenase, hyaluronidase, and elastase were assessed. Both extracts strongly reduced ROS levels, enhanced SOD activity, and significantly decreased pro-inflammatory cytokines. Bark extract also exhibited potent inhibitory activity against collagenase and elastase. UPLC-DAD-MS analysis revealed that both plant parts contained high levels of tannins; however, the leaf extract showed a more diverse composition, including more complex tannin forms and a significant amount of flavonoids from the quercetin and kaempferol class. In conclusion, H. virginiana leaf and bark extracts demonstrate multifunctional antioxidant and anti-inflammatory properties, supporting their potential use in cosmeceuticals and dermatological formulations targeting skin aging and inflammation. Full article

Background: Irradiation (IR) targets cancer cells, but also the tumor microenvironment, including the tumor’s blood vessels. In addition to tumor endothelial cell (TEC) apoptosis, IR can lead to TEC activation, potentially increasing immune cell infiltration. However, the changes underlying the IR-induced activation of endothelial cells (ECs) are poorly understood. This study investigated dose- and time-dependent molecular and functional responses of murine and human EC lines to IR in vitro and TECs in vivo in murine tumor models of colorectal carcinoma. Methods: HUVEC, EA.hy926, and Hulec5a, as well as murine bEND.3, 2H11, and SVEC4-10 EC lines, were irradiated with single doses of 2–10 Gy. EC proliferation and survival after IR were assessed by staining all nuclei (Hoechst 33342) and dead cells (propidium iodide) every 24 h for 5 days using the Cytation 1 Cell Imaging Multi-Mode Reader. RNA sequencing analysis of HUVECs irradiated with 2 Gy and 5 Gy at 24 h and 72 h after IR was conducted, focusing on processes related to EC activation. To validate the RNA sequencing results, immunofluorescence staining for proteins related to EC activation, including Stimulator of Interferon Response cGAMP Interactor 1 (STING), Nuclear factor kappa B (NF-κβ), and Vascular cell adhesion molecule 1 (VCAM-1), was performed. To validate the in vitro results, the response of TEC in vivo was analyzed using publicly available RNA sequencing data of TECs isolated from MC38 colon carcinoma irradiated with a single dose of 15 Gy. Finally, murine CT26 colon carcinoma tumors were immunofluorescently stained for STING and NF-κβ 24 and 48 h after IR with a clinically relevant fractionated regimen of 5 × 5 Gy. Results: Doses of 2, 4, 6, 8, and 10 Gy led to a dose-dependent decrease in proliferation and increased death of ECs. RNA sequencing analysis showed that the effects on the transcriptome of HUVECs were most pronounced 72 h after IR with 5 Gy, with 1014 genes (661 down-regulated and 353 up-regulated) being significantly differentially expressed. Irradiation with 5 Gy resulted in HUVEC activation, with up-regulation of the immune system and extracellular matrix genes, such as STING1 (log₂FC = 0.81) and SELE (log₂FC = 1.09), respectively; and down-regulation of cell cycle markers. Furthermore, IR led to the up-regulation of immune response- and extracellular matrix (ECM)-associated signaling pathways, including NF-κβ signaling and ECM–receptor interaction, which was also observed in the transcriptome of irradiated murine TECs in vivo. This was confirmed at the protein level with higher expressions of the EC activation-associated proteins STING, NF-κβ, and VCAM-1 in irradiated HUVECs and irradiated TECs in vivo. Conclusions: IR induces changes in ECs and TECs, supporting their activation in dose- and time-dependent manners, potentially contributing to the anti-tumor immune response, which may potentially increase the infiltration of immune cells into the tumor and thus, improve the overall efficacy of RT, especially in combination with immune checkpoint inhibitors. Full article

This paper provides an in-depth analysis of the microstructural characteristics and the chemical content of Polybutylene Terephthalate (PBT) composites that have different contents of Glass Fiber (GF). Blending of VALOX 420 (30 wt% GF/PBT) with unreinforced VALOX 310 allowed the composites to be prepared, with control of the concentration and distribution of the GF. The GF reinforcement and PBT matrix were characterized by an advanced microstructural spectrum and spatial analysis to show the influence of fiber density, dispersion, and chemical composition on performance. Findings indicate that GF content has a profound effect on microstructural properties and damage processes, especially traction effects in various regions of the specimen. These results highlight the significance of accurate control of GF during fabrication to maximize durability and performance, which can be used to inform the design of superior PBT/GF composites in challenging engineering applications. The implications of these results are relevant to a number of high-performance sectors, especially in automotive, electrical, and consumer electronic industries, where PBT/GF composites are found in extensive use because of their outstanding mechanical strength, dimensional stability, and thermal resistance. The main novelty of the current research is both the microstructural and chemical assessment of PBT/GF composites in different fiber contents, and this aspect is rather insufficiently studied in the literature. Although the mechanical performance or macro-level aging effects have been previously assessed, the Literature usually did not combine elemental spectroscopy or spatial microstructural mapping to correlate the fiber distribution with the damage mechanisms. Further, despite the importance of GF reinforcement in achieving the right balance between mechanical, thermal, and electrical performance, not much has been conducted in detail to describe the correlation between the microstructure and the evolution of damage in short-fiber composites. Conversely, this paper will use the superior spatial elemental analysis to bring out the effects of GF content and dispersion on micro-mechanisms like interfacial traction, cracking of the matrix, and fiber fracture. We, to the best of our knowledge, are the first to systematically combine chemical spectrum analysis with spatial mapping of PBT/GF systems with varied fiber contents—this allows us to give actionable information on material design and optimized manufacturing procedures. Full article

Brazil nuts (Bertholletia excelsa), mainly from the Amazon, are notable for their exceptionally high selenium (Se) content and are widely consumed as a natural dietary supplement. They also contain potentially harmful elements, including barium (Ba), and exhibit an unusual capacity to accumulate radioactive radium (Ra). In this study, we quantified the concentrations of Se, Ba, strontium (Sr), lanthanum (La), europium (Eu), and the radionuclides ²²⁶Ra and ²²⁸Ra, and assessed their in vitro bioaccessibility—data largely unavailable for these elements to date. Se was highly bioaccessible (≈85%), whereas Ba and Ra, both chemo- and/or radiotoxic, exhibited low bioaccessibility (≈2% each). Nuclear magnetic resonance (NMR) spectroscopy revealed Se to occur predominantly as selenomethionine (SeMet), alongside phytate, amino acids, peptides, and other polar low-molecular-weight compounds. The influence of Brazil nut flour (BNF) on Eu(III) speciation in simulated gastrointestinal fluids, and the effect of chelating agents such as ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), and the hydroxypyridinone 3,4,3-LI(1,2-HOPO) were investigated using time-resolved laser-induced fluorescence spectroscopy (TRLFS). Results indicate that the food matrix has only a minor impact on the decorporation efficacy of these chelators. These findings provide novel insights into the bioaccessibility and chemical speciation of nutritionally and toxicologically relevant elements in Brazil nuts. Full article

Achieving high mechanical performance in fiber-reinforced composites is essential for developing reliable and sustainable strengthening systems that aim to enhance service life and reduce the waste of resources. In particular, fiber rope composites, with their inherent flexibility and excellent structural properties, offer significant potential as reinforcement elements in strengthening applications. The mechanical properties of these composites could be further enhanced using a remarkably basic and fundamental method. In this study, this fundamental and effective method, nanoparticle modification, is presented at its most basic level. This research presents an experimental investigation into the mechanical behavior of 8 mm diameter carbon, basalt, and glass fiber rope composites, produced in both unmodified and graphene nanoplatelet (GNP)-modified forms. GNPs were reinforced into an epoxy matrix at weight fractions of 0.5%, 1%, and 2% to enhance the mechanical properties of the fiber rope composites. Fiber rope composites were fabricated using controlled mixing, molding, and curing techniques. Subsequently, a series of mechanical tests, including flexural, compressive, and buckling tests, were conducted to evaluate the impact of nanoparticle reinforcement on structural performance. The findings reveal that GNP modification leads to notable improvements in mechanical properties, suggesting that such enhanced composites may contribute to more resilient and long-lasting strengthening solutions. These results underscore the relevance of nanoparticle-enhanced composites in the context of material efficiency and end-of-life considerations in structural systems, particularly through extended usability and improved performance. Full article

Background/Objectives: Methamphetamine (METH), a potent psychostimulant, exerts harmful effects on the vascular system by promoting oxidative stress, inflammation, and endothelial injury. While its impact on the blood–brain barrier is well documented, its influence on the retinal microvasculature remains less understood. This study investigated the effects of METH on syndecan-1 expression and endothelial function in primary rat retinal microvascular endothelial cells (RRMECs) and isolated ophthalmic arteries. Methods: We assessed METH-induced changes in mRNA and protein expression levels of syndecan-1, matrix metalloproteinase (MMP)-2, and MMP-9. Endothelial function was evaluated using scratch migration assays and trans-endothelial electrical resistance (TEER) measurements. The mechanistic involvement of MMP-9 and trace amine-associated receptor 1 (TAAR-1), a known receptor for METH, was examined using selective pharmacological inhibitors. Results: METH exposure significantly decreased syndecan-1 expression and increased MMP-9 levels. These changes were accompanied by impaired endothelial migration and reduced TEER in RRMECs. Similar findings were confirmed in cultured ophthalmic arteries, reinforcing the translational relevance of our in vitro results. Inhibition of MMPs restored syndecan-1 expression and rescued endothelial function. Furthermore, TAAR-1 antagonism protected against syndecan-1 degradation, reduced MMP-9 upregulation, and improved endothelial migration and barrier resistance. Conclusions: Our findings suggest that METH induces loss of syndecan-1 and retinal vascular integrity by promoting TAAR-1–mediated MMP-9 upregulation. Targeting the TAAR-1/MMP-9 axis may offer a promising therapeutic strategy for preventing METH-induced microvascular damage in the retina. Full article

This paper establishes a rigorous theoretical framework for analyzing the existence and uniqueness of solutions to Cohen–Grossberg bidirectional associative memory neural networks (CGBAMNNs) incorporating four distinct types of time-varying delays: leakage, neutral, distributed, and transmission delays. This study makes three key contributions to the field: First, it overcomes the fundamental challenge posed by the system’s inherent inability to be expressed in vector–matrix form, which previously limited the application of standard analytical techniques. Second, the work develops a novel and generalizable methodology that not only proves sufficient conditions for solution existence and uniqueness but also, for the first time in the literature, provides an explicit representation of the unique solution. Third, the proposed framework demonstrates remarkable extensibility, requiring only minor modifications to be applicable to a wide range of delayed system models. Theoretical findings are conclusively validated through numerical simulations, confirming both the robustness of the proposed approach and its practical relevance for complex neural network analysis. Full article