Search Results (3,168)

This study addresses a two-dimensional anomalous solute transport process within a two-zone fractal porous medium. A mathematical formulation is developed to characterise transport phenomena in a non-homogeneous porous domain. The medium consists of two interacting regions: one containing mobile fluid and the other containing immobile fluid, between which mass transfer occurs. In the mobile-fluid region, solute transport is governed by the convection–diffusion equation. In contrast, the immobile-fluid region is described using a first-order kinetic model. The problem of solute injection through a designated boundary point is formulated and numerically implemented. The effects of anomalous transport behaviour on solute migration and filtration characteristics are examined. The study further evaluates the pressure field, filtration velocity distribution, and solute concentration in both zones. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer accounting for the majority of cases and exhibiting persistent challenges related to therapy resistance and metastatic progression. Increasing evidence indicates that dysregulated G protein-coupled receptor signaling and ion channel activity function cooperatively as master regulators of tumor cell proliferation, migration, survival, and therapeutic response. Cannabinoids, including phytocannabinoids such as delta-9-tetrahydrocannabinol and cannabidiol, as well as endogenous endocannabinoids, are uniquely positioned to modulate both G protein-coupled receptors and ion channels, thereby influencing key oncogenic signaling networks. This review synthesizes current knowledge on the role of major ion channel families, including transient receptor potential channels, potassium channels, and sodium channels, and principal G protein-coupled receptor pathways involved in lung cancer progression. We further discuss how cannabinoids reprogram these interconnected signaling systems through canonical cannabinoid receptors, non-classical targets such as G protein-coupled receptor 55 and adenosine receptors, and direct modulation of ion channel activity. Special attention is given to G protein-coupled receptor–ion channel coupling within membrane microdomains and to the capacity of cannabinoids to act as biased ligands, redirecting downstream pathways, such as the phosphoinositide 3-kinase–protein kinase B–mechanistic target of rapamycin and epidermal growth factor receptor signaling, toward apoptosis and reduced metastatic potential. Emerging strategies, including cannabinoid-based combination therapies, selective receptor biasing, and targeted delivery systems, are also highlighted. Altogether, cannabinoid-driven rewiring of G protein-coupled receptor and ion channel signaling represents a promising mechanistic framework for developing innovative therapeutic approaches against lung cancer. Full article

Characterizing surface runoff and the transport process of non-point source pollutants (NSPs) carried by this runoff is crucial for identifying key source areas, estimating pollution loads entering water bodies, and implementing pollution control, which is particularly important in regions dominated by smallholder farming in China. Currently, most of the commonly used NSP models originated from international countries and have shortcomings such as high data requirements, high generalization degrees, and requiring the calibration of numerous parameters in the application process. Therefore, a distributed non-point source pollution model based on the time-varying gain and stormwater runoff response was constructed, designed for application at the watershed scale. This study describes the construction of the model, introducing its principles and structure through three key modules: a rainfall–runoff module, a soil erosion module, and a pollutant migration and transformation module. The proposed model was used to simulate the rainfall–runoff, soil erosion, and nutrient migration and transformation processes at different spatiotemporal scales. Although it achieved the best performance at the monthly and annual scales, its simulation results at the daily and hourly scales still met the relevant requirements, with relative errors within 20% and Nash–Sutcliffe Efficiency (NSE) coefficients of approximately 0.7. The annual sediment delivery ratios for the Yangliu Small Watershed and the basin above the Ankang section in 2022 were determined to be 0.445 and 0.36, respectively. The pollutant processes corresponding to different runoff events in the Yangliu Small Watershed were simulated, and the average NSE for total nitrogen (TN), ammonia nitrogen (NH₃-N), nitrate nitrogen (NO₃-N), total phosphorus (TP), and soluble reactive phosphorus (SRP) were determined to be 0.69, 0.74, 0.79, 0.71, and 0.71, respectively. For the basin above the Ankang section, the NSE coefficients for the simulation of NH₃-N and TP pollutant processes were 0.78 and 0.83, respectively. The model demonstrated robust applicability across various spatial (ranging from small to large watersheds) and temporal (hourly−daily−monthly−annual) scales, and exhibited stability across different basins in a semi-humid region of China. The model is characterized by a parsimonious parameter set, ease of calibration, and strong spatiotemporal versatility, thus providing an efficient and reliable tool for non-point source pollution simulation. Full article

Background: research suggests that adolescents with a migrant background may be particularly vulnerable to behavioral addictions, including problematic gaming and Internet use. Methods: we compared Italian (ITA) and non-Italian (WIC) students on Internet Gaming Disorder (IGD) and Internet Addiction (IA) and examined whether coping strategies and interpersonal-relationship quality were associated with these outcomes, using robust linear models estimated with the GENLIN procedure in IBM SPSS Statistics 31 and regression-based models on observed variables. A total of 535 students (64.5% female; aged 9–18) completed the Video Games Addiction Questionnaire (VGA), the Internet Addiction Test (IAT), the Children’s Coping Strategies Checklist–Revised (CCSC), and the Assessment of Interpersonal Relations (AIR). Results: robust generalized linear models showed that WIC adolescents reported significantly higher IGD levels than their Italian peers, while no differences emerged for IA. Gender differences were evident only in unadjusted models, with males reporting higher IGD and females higher IA; however, these effects were not significant once age and nationality were considered simultaneously. Age was positively associated with IA but not with IGD. Avoidance coping was associated with higher levels of both IGD and IA, whereas active coping was negatively associated with IGD. Relationship quality was not associated with IGD but showed protective effects for IA: better relationships with mothers and with both male and female peers were associated with lower IA scores. Overall, the findings highlight that IGD and IA follow partially distinct developmental patterns. Migrant background emerged as a specific vulnerability factor for IGD, while IA appears more closely linked to age-related processes, coping styles, and interpersonal-relationship quality. Conclusions: the results call for differentiated prevention and intervention approaches targeting the distinct etiological mechanisms of each problematic behavior, focusing on coping and migration-related stress and belonging for IGD, and on strengthening coping repertoires and relational resources for IA. Full article

This paper investigates the formation mechanism and key influencing factors of freckle defects that arise during the directional solidification of a novel third-generation nickel-based single crystal superalloy turbine blade. A combined experimental and multi-physics numerical simulation approach was adopted. The results indicate that freckle formation primarily originates from solutal convection, which subsequently triggers a cascade of processes, including the development of convection-induced segregation channels, flow-driven dendrite fragmentation, and the migration and aggregation of dendrite fragments. The severity of freckling is closely dependent on both the casting’s position within the furnace and its local geometric characteristics. Castings located in regions with poorer heating conditions exhibit lower temperature gradients and slower solidification rates, significantly increasing their susceptibility to freckle formation. Similarly, on a given casting, the side subjected to less favorable heating is more prone to freckle initiation. The freckle number varies non-monotonically along the blade height, increasing from 3 to a maximum of 16, with a temporary decrease near the platform and a final reduction near the top. This trend is mainly attributed to thickness-dependent channel segregation, as well as freckle propagation into the interior and coalescence at higher positions. This study provides a crucial theoretical basis for understanding the formation mechanism of freckle defects in nickel-based single crystal superalloys and offers valuable guidance for optimizing blade manufacturing processes, reducing solidification defects, and enhancing blade quality and service performance. Full article

Nuclear lamins are the core molecular bridge linking the extracellular mechanical microenvironment to intranuclear gene regulation, and play a central regulatory role in cellular mechanosensation and mechanotransduction. Here, we systematically integrate the latest global research progress on nuclear lamins, delineating the cascade regulatory mechanism by which lamins mediate the transmission of mechanical signals across the nuclear envelope and the subsequent regulation of chromatin remodeling and epigenetic modification, with a focus on the molecular characteristics and functional specificity of distinct nuclear lamin subtypes and their interaction modes with the Linker of Nucleoskeleton and Cytoskeleton complex (LINC complex) and chromatin. Existing studies have established that nuclear lamins are mainly divided into three categories: A-type lamins (Lamin A/C), B-type lamins (Lamin B1, B2), and germ cell-specific subtypes. Among these, A-type lamins directly determine the mechanical stiffness of the nucleus and serve as the core mediators of intranuclear mechanical signal transduction. Each subtype of B-type nuclear lamins has a well-defined, non-redundant functional division: Lamin B1 and Lamin B2 indirectly maintain nuclear structural stability and regulate epigenetic status by anchoring facultative heterochromatin and constitutive heterochromatin, respectively. Notably, Lamin A/C distributed in the nucleoplasm also bears significant mechanical tension, which challenges the long-standing view that the mechanical functions of nuclear lamins are restricted to the nuclear envelope region. After mechanical force is transmitted across the nuclear envelope to nuclear lamins via the LINC complex, it can regulate the spatial conformation of chromatin and epigenetic modifications, thereby determining core cellular life activities including proliferation, differentiation, and migration. Dysregulation of this pathway is closely associated with a wide spectrum of human diseases, including cardiovascular diseases, progeria, muscular dystrophy, and neurodevelopmental disorders. Taken together, this review systematically delineates the hierarchical regulatory network of the “LINC complex–nuclear lamina–chromatin” axis, advances our understanding of the fundamental principles of cellular mechanobiology, and provides a theoretical framework for deciphering the pathological mechanisms and developing targeted therapeutic drugs for related diseases. Full article

Background/Objectives: Vascular inflammation and impaired endothelial regeneration contribute to chronic degenerative disorders, including ocular neovascularization and retinal degeneration. Nutritional bioactives that modulate molecular pathways governing angiogenesis and tissue remodeling represent promising adjunct strategies for vascular health. This study investigated whether cocoa powder (CP) regulates hypoxia-driven molecular signaling and attenuates vascular inflammation and degeneration. Methods: The vascular-modulatory effects of CP were examined in human umbilical vein endothelial cells (HUVECs) and in murine models of alkali-induced corneal neovascularization and N-methyl-N-nitrosourea (MNU)-induced retinal degeneration. Hypoxia-inducible factor-1α (HIF-1α) signaling and downstream angiogenic targets were assessed by Western blotting and quantitative PCR. Endothelial migration, tube formation, and transwell assays were performed to evaluate angiogenic responses. In vivo, oral CP (50 or 200 mg/kg) was administered, and vascular growth, inflammatory and remodeling markers, and retinal structural integrity were analyzed by histology, immunofluorescence, and protein expression. Results: At non-cytotoxic concentrations (0.1–1.0 μg/mL), CP suppressed hypoxia-induced HIF-1α protein stabilization without altering HIF-1α mRNA levels and reduced expression of VEGFA, EPO, and GLUT1. CP significantly inhibited VEGF-A-induced endothelial migration, network formation, and chemotactic invasion. In alkali-injured corneas, CP reduced the neovascularized area and downregulated VEGF, MMP2, MMP9, α-smooth muscle actin, and Ninj1, indicating attenuation of vascular inflammation and fibrotic remodeling. In the MNU model, CP preserved outer nuclear layer thickness, reduced glial activation (GFAP), maintained rhodopsin expression, and decreased MMP9 induction. Conclusions: CP functions as a nutritional modulator of hypoxia-responsive and inflammatory pathways, suppressing pathological angiogenesis while supporting structural preservation in degenerative vascular conditions. These findings highlight the translational potential of dietary polyphenol-rich interventions in regulating vascular inflammation and regeneration. Full article

Ballast compaction is a critical factor influencing ballast bed condition and the operational safety of heavy-haul railways. However, existing quantitative evaluation methods often suffer from overly idealized simulation models and limitations in signal processing and assessment frameworks. To address these issues, this study proposes a quantitative analysis approach for ballast compaction by integrating non-uniform medium simulation modeling, wavelet–Singular Value Decomposition (SVD) joint denoising, frequency–wavenumber (F-K) migration imaging, and wavelet packet decomposition (WPD)-based feature extraction. Forward simulations were conducted based on the constructed model, and the proposed methodology was validated using 1.5 GHz (gigahertz, 1 GHz = ${10}^9$ Hz) ground penetrating radar (GPR) data acquired from compaction experiments. The results demonstrate that wavelet–SVD joint denoising effectively suppresses deep coherent noise caused by strong reflections from sleepers, significantly enhancing the identification of deep effective signals and ensuring accurate localization and feature extraction of compaction zones. The Geometric Mean of WPD High/Low-Frequency Energy Ratio (GMHLFER) exhibits a strong positive correlation with the degree of compaction. In simulations, as the proportion of compacted material increased from $9\%$ to $21\%$, the GMHLFER rose from 21.555 to 26.581. In field tests, the value increased from 22.012 to 26.012 as compaction severity progressed from slight to severe, demonstrating stable responses across full-gradient compaction conditions and indicating high robustness and sensitivity. The proposed method provides an effective approach for quantitative characterization of ballast compaction in heavy-haul railways, and offers a promising technical pathway for intelligent inspection and condition assessment of railway ballast beds. Full article

Glioblastoma cells sustain tumor growth by releasing inflammatory cytokines that modulate the tumor microenvironment (TME). Targeting the cytokine expression profile of glioblastoma multiforme (GBM) and tumor-supportive cells represents a promising therapeutic strategy. Lactoferrin, a natural compound with recognized anticancer properties, has been poorly investigated regarding its role in modulating GBM cytokine profiles and TME cellular activity. This study evaluated lactoferrin’s ability to modulate GBM inflammatory signaling and pro-tumorigenic functions of tumor-associated astrocytes. U87MG glioblastoma cells were treated with human lactoferrin (10 μg/mL) for 72 h, and DI-TNC1 astrocytes were exposed to conditioned medium from treated and untreated U87MG cells for 24 h. Results demonstrate that lactoferrin inhibits GBM cell proliferation, migration, and stemness-related pathways while modulating inflammatory profiles through NF-κB pathway interference, downregulating pro-tumorigenic cytokines IL-6, IL-1β, IL-4, and IL-10. Increased TGF-β expression in lactoferrin-treated cells likely reflects a compensatory mechanism rather than enhanced malignancy. Furthermore, lactoferrin attenuates pro-tumorigenic effects of tumor-associated astrocytes by reducing NF-κB activation and expression of TGF-β, TNF-α, IL-4, and IL-10. This innovative study provides evidence supporting non-cytotoxic approaches targeting GBM-TME interactions, highlighting lactoferrin’s potential to attenuate glioblastoma malignancy and astrocyte inflammatory signaling, suggesting its therapeutic potential for GBM treatment. Full article

Extracellular vesicles (EVs) derived from microbial sources, including beer yeast (Saccharomyces cerevisiae), have recently attracted increasing attention as bioactive nanostructures with potential biomedical and cosmetic applications. In this study, EVs were isolated from Saccharomyces cerevisiae (beer yeast) using an electrokinetic ion-binding filtration system, followed by tangential flow filtration (TFF)-based buffer exchange. Their physicochemical characteristics and hair follicle-related biological activities were systematically evaluated. Nanoparticle tracking analysis demonstrated a mean particle size within the typical EV range, and zeta potential analysis confirmed a negatively charged surface. Cryo-transmission electron microscopy further verified the presence of lipid bilayer-enclosed nanovesicles. Biological activity was assessed in human dermal papilla cells, keratinocytes, and dermal fibroblasts, which collectively represent key components of the hair follicle microenvironment. At non-cytotoxic concentrations, yeast-derived EVs enhanced dermal papilla cell proliferation and promoted keratinocyte migration. The EVs attenuated pro-inflammatory cytokine expression under stimulated conditions and upregulated collagen-related gene expression in dermal fibroblasts. In addition, measurable antioxidant activity was observed. Collectively, these findings indicate that S. cerevisiae-derived extracellular vesicles exhibit multifunctional bioactivity relevant to the regulation of hair follicle-associated cellular processes. This study supports the potential of microbial EVs as scalable bioactive platforms for modulating hair follicle microenvironmental homeostasis. Full article

Background/Objectives: The G protein-coupled oestrogen receptor (GPER) has anti-tumorigenic effects in several human cancers. However, its role in prostate cancer (PCa) remains incompletely defined. The present study investigated GPER’s role in targeting the hallmarks of PCa. Methods: Tissue microarrays were used to analyse GPER immunoexpression in PCa samples. Non-neoplastic (PNT1A) and neoplastic (LNCaP, DU145 and PC3) prostate cells were treated with the GPER-specific agonist, G1. Cell viability, proliferation, cell cycle, apoptosis, migration and invasion were evaluated. Glucose consumption, lactate production, lactate dehydrogenase activity and oxidative status were determined spectrophotometrically. Results: GPER immunoreactivity was higher in PCa than in benign prostatic hyperplasia and inversely correlated with PSA serum levels. G1 modulated GPER subcellular location in prostate cells, being detected at the cell membrane, endoplasmic reticulum, and residually in the nucleus. GPER activation decreased cell viability and proliferation, induced cell cycle arrest at G2/M phase, and increased PCa cells apoptosis. Additionally, GPER activation inhibited the migration and invasion of DU145 cells, and long-term exposure to G1 reduced epithelial–mesenchymal transition, an effect not observed in PC3 cells, indicating the importance of cell-specific contexts. Our results also showed that G1 treatment modulated the metabolic profile of PCa cells, changing glucose, amino acids and lipid metabolism. Finally, G1 increased oxidative stress in PCa cells. Conclusions: Overall, this study demonstrated that GPER activation affects a broad range of PCa hallmarks. These findings support an anti-cancer role for GPER in PCa and encourage further exploration of its action in regulating metabolism and as a therapeutic target. Full article

Atherosclerosis (AS) is a cardiovascular disease characterized by diverse etiological factors and complex pathological mechanisms. In recent years, the role of long non-coding RNAs (lncRNAs) in AS has received increasing attention. Research shows that lncRNAs regulate key biological processes involved in AS, such as vascular endothelial function, proliferation and migration of vascular smooth muscle cells (VSMCs), macrophage polarization, and lipid metabolism, through various mechanisms, including epigenetic modification, transcriptional regulation, and post-transcriptional control. As important components of traditional medicine, Chinese herbal monomers and compounds have been found to modulate the expression of lncRNAs, thereby improving vascular endothelial function, reducing lipid deposition, and inhibiting inflammatory responses, ultimately exerting anti-atherosclerotic effects. This review systematically examines the role of lncRNAs in the disease mechanism of AS and summarizes recent advances in Traditional Chinese Medicine (TCM) interventions targeting lncRNA expression for the treatment of AS, offering new insights and directions for the prevention and management of AS with Chinese medicine. Full article

Background/Objectives: Alloantigen H is one of thirteen systems in the chicken. Little is known about this system which has two serological alleles. The objectives of this study were (1) to identify the genetic region encoding the chicken alloantigen H, and (2) to develop DNA detection-based methods to aid H system allele identification. Methods: SNP genotypes from Axiom chicken SNP arrays were established for samples with known H system serological types. Sources of DNA included two elite Hy-Line White Leghorn lines segregating for alloantigen H, non-pedigreed samples from the Northern Illinois University (NIU) DNA bank, plus inbred line samples. Sequence information was also available for the commercial and inbred lines. Results: GWAS results from the elite Hy-Line lines and NIU DNA bank samples showed a very strong peak in the same 4.20–4.30 Mbp region on chromosome 24. Predicted cell membrane expression and the presence of non-synonymous SNP were criteria to identify candidate genes. Seven genes in this region have membrane-associated products: MCAM (CD146), THY1, MFRP, CLDN25, KCNJ14L, ABCG4, and PDZD3. However, only MCAM had an SNP variation that matched the serological haplotypes. Lines known to be segregating for the H system had concordance rates between serological results and SNP haplotype of 95% for both the elite HYL lines and 99% for the NIU samples, indicating that the MCAM (CD146) gene encodes the chicken H blood system. Conclusions: The gene product is a cell adhesion molecule affecting multiple activities including angiogenesis, development, cell differentiation, cell migration, signaling transduction, and immune responses. Long, short, and soluble isoforms are found in chickens. The described DNA-based typing methods facilitate future investigations to examine H haplotype frequencies in lines with identified differential responses such as growth or immune responses. Determining H haplotype association with egg production, feed conversion, and other traits with economic importance will aid in determining the significance of this immune-related gene in overall poultry health. Full article

This study analyzes the performance of the double robust estimator to compute the treatment effect, not only at the mean but also in the tails in a Monte Carlo experiment. While previous research focused on shifting the regression component of the double robust estimator toward the tail, here we focus on the behavior of the propensity score away from the mean. Investigating the tails of the regression outcome allows for a closer look at the observations that are either highly or poorly responsive to treatment. Examining the tails of the propensity score distribution scrutinizes the observations with a higher or lower probability of being treated, which can be non-constant and even asymmetric. The goal is to assess the behavior of the double robust estimator when both components are computed away from the sample mean, in the tails of the treatment and control distributions. A case study on Italian education concludes the analysis. We find a positive double robust difference in higher education across regions, larger at the top location, due to the significant internal migration of qualified workers toward the northern regions. Women’s employment is higher for highly educated women, and gender has a significant impact: the analysis of the mismatch between probabilities and outcomes signals that women achieve higher education at rates exceeding their probabilities; they are more likely to exceed their predicted likelihood of attaining higher education. Full article

Background/Objectives: The effects of silver-coated dressing on wound healing, including cytotoxicity, are controversial due to the limited and incongruous results of in vitro versus in vivo research. Multiple factors intervene in wound healing processes and scarring, including pro/anti-inflammatory and pro/anti-fibrosis markers. Herein, to elucidate reported differences between in vitro and in vivo results, the effects of silver-coated dressing on 2D and 3D mono- and cocultures of fibroblasts and adipose-derived stem cells (ADSC) were investigated. Methods: Migration profiles in 2D and 3D assays, α-smooth muscle actin and proliferation marker Ki-67 expression, TGF-β1, TGF-β3, IL-6 and IL-10 levels and/or gene expression were assessed on four culture constructs. Results: In 2D systems at 24 h, silver-treated ADSC monocultures displayed better migration abilities compared to cocultures with high fibroblast ratio. In contrast, changes in the sprouting pattern between treated and untreated samples were non-significant in 3D constructs. TGFβ-1 levels decreased post-treatment, while TGFβ-3 increased, especially in 3D models. IL-6 gene expression was up-regulated following silver exposure in 3D models, mainly for stem cells in mono- and cocultures. Conclusions: Experiment data on 3D constructs suggest that silver-coated dressings do not significant impede wound healing, whereas cytotoxic effects were more pronounced in the 2D cultures. These inconsistencies, also noted in the literature, invite a methodological discussion of the 2D setup implications, recommending 3D constructs as a more appropriate evaluation standard where observable effects are closer to in vivo conditions and more relevant for transfer to clinical applications. Full article