Search Results (2,938)

In response to the growing complexity of global exploration targets, traditional Euclidean geometric and linear statistical methods reveal inherent theoretical limitations in characterizing hydrocarbon reservoirs as complex geological bodies that exhibit simultaneous local disorder and global order. Fractal theory, with its core parameter systems such as fractal dimension and scaling exponents, provides an innovative mathematical–physics toolkit for quantifying spatial heterogeneity and resolving the multi-scale characteristics of reservoirs. This review systematically consolidates recent advancements in the application of fractal theory to oil and gas resource assessment, with the aim of elucidating its transition from a theoretical concept to a practical tool. We conclusively demonstrate that fractal theory has driven fundamental methodological progress across four critical dimensions: (1) In reservoir classification and evaluation, fractal dimension has emerged as a robust quantitative metric for heterogeneity and facies discrimination. (2) In pore structure characterization, the theory has successfully uncovered structural self-similarity across scales, from nanopores to macroscopic vugs, enabling precise modeling of complex pore networks. (3) In seepage behavior analysis, fractal-based models have significantly enhanced the predictive capacity for non-Darcy flow and preferential migration pathways. (4) In fracture network modeling, fractal geometry is proven pivotal for accurately characterizing the spatial distribution and connectivity of natural fractures. Despite significant progress, current research faces challenges, including insufficient correlation with dynamic geological processes and a scarcity of data for model validation. Future research should focus on the following directions: developing fractal parameter inversion methods integrated with artificial intelligence, constructing dynamic fractal–seepage coupling models based on digital twins, establishing a unified fractal theoretical framework from pore to basin scale, and expanding its application in low-carbon energy fields such as carbon dioxide sequestration and natural gas hydrate development. Through interdisciplinary integration and methodological innovation, fractal theory is expected to advance hydrocarbon resource assessment toward intelligent, precise, and systematic development, providing scientific support for the efficient exploitation of complex reservoirs and the transition to green, low-carbon energy. Full article

Background: Cannabinoids, such as tetrahydrocannabinol (∆-9-THC) and cannabidiol (CBD) have been proposed for topical medicinal use as a treatment for tissue inflammation. In this context, keratinocytes are the first cells that encounter cannabinoids. The present study evaluated the dose–response relationship between different concentrations of THC and CBD and their effects on human skin and gingival keratinocyte growth and migration, to identify suitable non-toxic concentrations of cannabinoids. Methods: Human gingival and skin keratinocytes were exposed to CBD or THC at different concentrations for 24 h, and then cell adhesion, morphology, and growth/viability were assessed. The effects of cannabinoids on keratinocyte migration were evaluated at 6, 12, and 24 h. Cytotoxicity of CBD and THC against keratinocyte cells was assessed using an LHD cytotoxicity test. Cell metabolic profiles were evaluated using Mito and Glyco Stress Assays. The anti-inflammatory effects of cannabis derivatives were assessed against LPS-stimulated keratinocytes. Data analysis was performed by one-way ANOVA. Results: Only high concentrations (10 and 20 μg/mL) of CBD and THC were cytotoxic to gingival and skin keratinocytes, reduced cell adhesion and growth, and were associated with a delay in cell migration after wounding. Cells exposed to high concentrations (20 μg/mL) of cannabinoids displayed high levels of lactate dehydrogenase (LDH) activity and changes in mitochondrial activities. CBD induced a metabolic shift in skin keratinocyte cells toward glycolysis, while reducing mitochondrial oxidative phosphorylation. In contrast, THC did not alter the metabolic profile of skin keratinocytes. Interestingly, both CBD and THC significantly reduced the LPS-induced inflammatory response by decreasing secretion of IL-6 and IL-8 by gingival and skin keratinocytes. Conclusions: Gingival and skin keratinocytes interact differently with cannabinoids. Only high concentrations of cannabinoids were cytotoxic, suggesting that the use of low concentrations of CBD and THC for topical medicinal applications may help control tissue inflammation. Full article

As a common substitute for brominated flame retardants (BFRs), organophosphate flame retardants (OPFRs) have been insufficiently studied in terms of their ecotoxicological impacts on plastic biodegradation processes in invertebrate systems. This study investigated the impact of an OPFR, tris (1-chloro-2-propyl) phosphate (TCPP), on the dietary behavior and gut microbiota of Galleria mellonella (Linnaeus, 1758) (Lepidoptera: Pyralidae) larvae during the biodegradation of rigid polyurethane (RPU), as well as the fate of TCPP. The results show that TCPP interfered with larval feeding activity, hindered the nutritional conversion of food, and triggered metabolic compensation through lipid reserve catabolism. Notably, mass balance analysis revealed that bioaccumulation of TCPP was negligible, with most of it excreted through frass, indicating limited biodegradation of this organophosphate ester. 16S rRNA sequencing indicated that TCPP drove the reconstruction of gut microbiota in larvae and identified three dominant bacteria of Morganellaceae, Enterobacteriaccae, and Staphylococcaceae families, as well as non-dominant bacteria of Klebsiella and Vagococcaceae families, as characteristic microbiota contributing to RPU and TCPP biotransformation. This study serves as a reminder to pay attention to the toxicity, migration, and transformation of OPFRs in biodegradable plastics. Notably, TCPP, a dominant chlorinated OPFR, exhibits environmental persistence with limited biodegradability and low bioaccumulation, traits which hinder the spontaneous attenuation of plastic waste in ecosystems and undermine the sustainability of the plastic lifecycle. This work emphasizes the need to integrate risk assessments of specific additives into the plastic waste management framework and to develop targeted detoxification strategies for promoting a sustainable material lifecycle. Full article

Recent clinical trials have shown significant cardioprotective effects of antidiabetic sodium-glucose cotransporter 2 inhibitors (SGLT2i), including canagliflozin, empagliflozin, and dapagliflozin. These drugs significantly reduce hospitalizations for heart failure with reduced and preserved ejection fraction in both diabetic and non-diabetic patients. Yet, the mechanisms underlying their protective effects, beyond their glucose-lowering properties, remain poorly understood. This study aimed to elucidate the direct effects of SGLT2i on cardiac fibroblasts, key mediators of myocardial fibrosis, ventricular remodeling, and heart failure. Using primary human cardiac fibroblast cultures, we compared the impact of canagliflozin, empagliflozin, and dapagliflozin on fibroblast properties. All three inhibitors significantly prevented myofibroblast differentiation. Notably, only canagliflozin significantly reduced fibroblast proliferation and migration. While all SGLT2i increased AMP-activated protein kinase (AMPK) phosphorylation, their effects on myodifferentiation were AMPK-independent. In contrast, the effect of canagliflozin on migration was partially dependent on AMPK, as demonstrated using the AMPK inhibitor BAY-3827. These findings reveal distinct cellular effects of individual SGLT2i on cardiac fibroblasts, suggesting heterogeneous potential to modulate extracellular matrix remodeling. Among them, canagliflozin may be more potent in preventing myocardial fibrosis in the context of heart failure. Full article

The quality of groundwater, a crucial freshwater resource in cold regions, directly affects human health. This study used groundwater quality monitoring data collected in the central Songnen Plain in 2014 and 2022 as a case study. The improved DRASTICL model was used to assess the vulnerability index, while water quality indicators were selected using a random forest algorithm and combined with the entropy-weighted groundwater quality index (E-GQI) approach to realize water quality assessment. Furthermore, self-organizing maps (SOM) were used for pollutant source analysis. Finally, the study identified the synergistic migration mechanism of NH₄⁺ and Cl⁻, as well as the activation trend of As in reducing environments. The uncertainty inherent to health risk assessment was considered by developing a kernel density estimation–trapezoidal fuzzy number–Monte Carlo simulation (KDE-TFN-MCSS) model that reduced the distribution mis-specification risks and high-risk misjudgment rates associated with conventional assessment methods. The results indicated that: (1) The water chemistry type in the study area was predominantly HCO₃⁻–Ca²⁺ with moderately to weakly alkaline water, and the primary and nitrogen pollution indicators were elevated, with the average NH₄⁺ concentration significantly increasing from 0.06 mg/L in 2014 to 1.26 mg/L in 2022, exceeding the Class III limit of 1.0 mg/L. (2) The groundwater quality in the central Songnen Plain was poor in 2014, comprising predominantly Classes IV and V; by 2022, it comprised mostly Classes I–IV following a banded distribution, but declined in some central and northern areas. (3) The results of the SOM analysis revealed that the principal hardness component shifted from Ca²⁺ in 2014 to Ca²⁺–Mg²⁺ synergy in 2022. Local high values of As and NH₄⁺ were determined to reflect geogenic origin and diffuse agricultural pollution, whereas the Cl⁻ distribution reflected the influence of de-icing agents and urbanization. (4) Through drinking water exposure, a deterministic evaluation conducted using the conventional four-step method indicated that the non-carcinogenic risk (HI) in the central and eastern areas significantly exceeded the threshold (HI > 1) in 2014, with the high-HI area expanding westward to the central and western regions in 2022; local areas in the north also exhibited carcinogenic risk (CR) values exceeding the threshold (CR > 0.0001). The results of a probabilistic evaluation conducted using the proposed simulation model indicated that, except for children’s CR in 2022, both HI and CR exceeded acceptable thresholds with 95% probability. Therefore, the proposed assessment method can provide a basis for improved groundwater pollution zoning and control decisions in cold regions. Full article

Background: Migration phenomena from low- to high-income countries have been constantly increasing in the past years, and migrants living with HIV (MLHIVs) currently represent a non-negligible proportion of the population living with HIV in the European setting. When taken into care, MLHIVs should be screened for tropical diseases capable of asymptomatically persisting for years and leading to severe and/or chronic complications, especially in immunocompromised populations. Methods: We conducted a retrospective study aimed at analyzing the screening ratios and seroprevalences of strongyloidiasis, schistosomiasis, and Chagas disease among MLHIVs who attended a tertiary care hospital outpatient clinic in Florence, Italy. Results: Between 2014 and 2023, 251 MLHIVs were enrolled, of which 85 (33.9%), 137 (54.6%), and 219 (87.3%) were at risk for schistosomiasis, Chagas disease, and strongyloidiasis, respectively. Among individuals at risk for each of these parasitic diseases, 43.4% were screened for strongyloidiasis, 25.9% for schistosomiasis, and 65.0% for Chagas disease, with a seroprevalence of 5.3%, 13.6%, and 0%, respectively. Conclusions: While confirming the relevant burden of neglected parasitic diseases in the MLHIV population, our results suggest the need to improve awareness of these diseases even in the specialist context in order to reduce underdiagnoses and the risk of severe complications, especially in particularly vulnerable groups of the population. Full article

Background: Extensive skin injuries from severe burns or chronic non-healing ulcers overwhelm the body’s natural repair mechanisms, while current therapeutic approaches relying on autologous skin grafting are limited by donor site availability. Three-dimensional epithelial spheroid cultures enhance stem cell regenerative potential, but standardized comparative methodologies are lacking. Methods: We established a comprehensive framework comparing scaffold-free and scaffold-based epithelial spheroid systems using HaCaT keratinocytes. High-throughput approaches utilized BioFloat and ELPLASIA 96-well platforms, while low-throughput 6-well ULA plates generated heterogeneous populations (holospheres, merospheres, paraspheres). Scaffold-based studies embedded spheroids in Matrigel to evaluate outgrowth capacity. ROCK1 inhibitor treatment was assessed for stemness enhancement. Results: High-throughput systems generated uniform spheroids with high reproducibility and consistent circularity. Low-throughput cultures produced heterogeneous populations with distinct size distributions (holospheres: 408.7 μm², merospheres: 99 μm², paraspheres: 14.1 μm²). In Matrigel scaffolds, merospheres and paraspheres migrated outward, forming epithelial sheets, while holospheres remained intact as BMI-1+ stem cell reservoirs. ROCK1 inhibition enhanced holosphere formation, preserved stemness markers, and reduced premature differentiation. Conclusions: This standardized toolbox demonstrates scaffold-free systems optimize scalability for screening while scaffold-based approaches enable physiologically relevant regenerative studies. Integration of both methodologies provides flexibility matching experimental design to scientific objectives, accelerating translation to clinical applications. Full article

This study investigates the mechanisms of hazardous gas outbursts in geologically complex non-coal tunnels. This is a critical safety concern during excavation, particularly at specific locations and during time-sensitive periods. To address this, a gas–solid coupled numerical model is established to simulate gas seepage processes under such conditions. The simulations systematically reveal the spatiotemporal evolutionary patterns of the velocity and direction of the gas seepage and elucidate the migration mechanism driven by excavation-induced pressure gradients. The model specifically analyzes how geological structures, such as rock joints and fractures, control the seepage pathways. The model also demonstrates the dynamic variations in and enrichment behavior of the gas escape velocities near these discontinuities. Field measurements obtained from the Hongdoushan Tunnel validated the simulated emission patterns along jointed fissures. The findings clarify the intrinsic relationships between the outburst dynamics and key factors that include pressure differentials, geological structures, and temporal effects. This work provides a crucial theoretical foundation and practical strategy for the prediction and prevention of hazardous gas disasters in analogous tunnel engineering projects, thereby enhancing overall construction safety. Full article

Given world immigration patterns, understanding immigrant children’s social inclusion is crucial, especially the role of school characteristics. The current study examines how individual- and school-level factors shape immigrant children’s peer relationship In Ireland, a context that has experienced rapid demographic change by remains underexplored in the literature. Drawing on social network theory, we analyse data from 2244 primary school children across 98 schools, using measures of peer group size, friendship nominations, and network centrality to capture social inclusion. Multilevel regression models show that immigrant children report smaller peer groups compared to non-immigrant peers, while minority language use is consistently associated with lower levels of social centrality. Contrary to expectations, school size and urbanicity had limited effects, and classrooms with a higher proportion of immigrant students were associated with reduced inclusion overall, although immigrant children themselves benefitted somewhat from greater classroom diversity. Family affluence was positively associated with all measures of inclusion, highlighting the role of socioeconomic inequalities alongside migration background. The findings underscore the complex and multifaceted nature of social inclusion, showing that both structural and interpersonal dynamics shape immigrant children’s experiences in Irish schools, and pointing to the need for targeted strategies to address linguistic and socioeconomic barriers. Full article

The dual assessment of environmental risks and energy consumption of solid waste is crucial for ensuring environmental safety and energy consumption management. Using risk assessment tools to inform best management practices for reclamation is very important. In this paper, a former Extended Environmental Multimedia Modeling System (EEMMS) combined with the Monte Carlo Method (MCM) of risk assessment was further used for exploring the fate and migration of pollutant leakage in the CFSWMA landfill. Specifically, MODFLOW combined with the EEMMS–MCM system has been applied using Biochemical Oxygen Demand (BOD) as a typical indicator to model the behavior of leachate components. An EEMMS–MCM integrated risk assessment for a 20-year period was conducted. The case study of BOD emissions from the CFSWMA landfill shows that even the leachate did not have a serious impact on Canadian territory during the 20 years; however, non-sorption chemicals are mainly affected by the groundwater flow, whereas sorption chemicals are affected by the partition coefficient (or sorption). Further, this study introduces energy consumption factors such as soil and surface water bodies, and constructs an integrated dual assessment framework for the environmental risks and energy consumption of pollutants. In summary, by integrating the EEMMS pollutant migration model with an environmental risk and energy consumption assessment, a dual assessment of environmental risks and energy consumption is achieved. Full article

Neuroinflammation is a key response to disturbed CNS homeostasis, largely mediated by activated microglia, and excessive microglia-driven inflammation can negatively impact neurogenesis. ZEB1 plays a crucial role in neurogenesis and brain development by influencing neural stem cell (NSC) maintenance, proliferation, and differentiation. This study aimed to evaluate how the knockdown of ZEB1 influences the behavior of NSCs in inflammatory environments. NSCs were isolated from the subventricular zone of rats, and ZEB1 knockdown was achieved using ZEB1 siRNA. A conditioned medium derived from lipopolysaccharide-activated microglia was utilized to induce inflammatory responses in NSCs. The silencing of ZEB1 in NSCs significantly reduced the expression of ZEB1. Furthermore, ZEB1 knockdown in NSCs resulted in a significant decrease in neurosphere formation, cell migration ability, reactive oxygen species generation, and various cytokine levels under both non-inflammatory and inflammatory conditions. These findings reveal the regulatory role of ZEB1 in the modulation of NSC behavior, suggesting that targeting ZEB1 may provide a potential therapeutic strategy for neuroinflammatory CNS disorders. Full article

This study investigates the determinants of Romanian workers’ migration intentions towards Italy, integrating economic, social, and psychological perspectives. Based on a sample of 358 respondents, four hypotheses were tested concerning perceived living standards, working conditions, quality of public services, and anticipated integration difficulties. Data were analysed using descriptive statistics, Spearman’s rho correlation, Mann–Whitney U, Chi-square, ANOVA, and ordinal logistic regression. The results confirm that higher perceived living standards and better working conditions in Italy significantly increase the likelihood of expressing migration intentions, while favourable evaluations of healthcare and education act as additional pull factors. Conversely, anticipated integration difficulties, particularly language barriers and cultural adaptation, reduce migration intentions, indicating that socio-psychological obstacles can counterbalance economic incentives. By combining non-parametric and multivariate analyses, the study demonstrates that migration is a multidimensional process shaped not only by structural opportunities but also by behavioural and psychological appraisals. These findings are consistent with recent research on European labour mobility and contribute to the literature by highlighting the role of subjective perceptions in shaping migration decisions. Implications for policy include the need to address both economic disparities and integration barriers to support more balanced mobility within the European space. Full article

Predicting how vegetation–debris interactions reshape alternate sandbars under a steady subcritical flow remains poorly understood in laboratory-to-field scaling. This study quantified how vegetation density and layout interact with debris geometry to control scouring and deposition and developed an empirical tool to predict normalized bed-level changes. Flume experiments investigated how vegetation–debris interactions regulate the hydromorphodynamics of non-migrating alternate sandbars under a steady subcritical flow (Q = 0.003 m³/s; slope = 1/200). Vegetation patches were configured in two spatial layouts—upstream (apex) and river line (edge), at varying densities, with and without debris (I-type: wall-like; U-type: horseshoe-shaped). Results indicated that dense upstream vegetation combined with I-type debris produced the strongest morphodynamic response, generating maximum scour, corresponding to the maximum bed-elevation changes (Δz) normalized by water depth (h) (dimensionless Δz/h) values of −1.55 and 1.05, and sustaining more than 70% of the downstream morphodynamic amplitude. In contrast, U-type debris promoted distributed deposition with a milder scour, while sparse vegetation yielded weaker, more transient responses. Debris geometry-controlled flow partitioning: the I-type enhanced frontal acceleration, whereas the U-type facilitated partial penetration and redistribution. To integrate these findings into predictive frameworks, an empirical regression model was developed to estimate Δz/h from the vegetation density, distribution, and debris geometry, with an additional blockage index to capture synergistic effects. The model achieved 87.5% prediction within ±20% error, providing a practical tool for anticipating scour and deposition intensity across eco-hydraulic configurations. These insights advance intelligent water management by linking morphodynamic responses with predictive modeling, supporting flood-resilient river engineering, adaptive channel stability assessments, and nature-based solutions. Full article

P2Y₂ receptors are a subclass of G protein-coupled receptors activated by the extracellular nucleotides ATP and UTP. These receptors are widely expressed in multiple tissues—including the brain, lungs, heart, and kidneys—and play pivotal roles in inflammation, wound healing, and cell migration. Through coupling with various G proteins, P2Y₂ receptors initiate diverse intracellular signaling pathways that mediate calcium mobilization, cytokine release, and cytoskeletal reorganization. Recent studies highlight their dual roles in health and disease. In physiological contexts, P2Y₂ receptors contribute to immune modulation and tissue repair. In pathological conditions, they are implicated in Alzheimer’s disease by promoting non-amyloidogenic processing of amyloid precursor protein and in dry eye disease by enhancing mucin secretion while modulating ocular inflammation. They also influence chloride secretion and mucosal hydration in cystic fibrosis and contribute to inflammatory regulation and epithelial repair in inflammatory bowel disease. Additionally, P2Y₂ receptors modulate breast cancer progression by regulating cell adhesion, migration, and matrix remodeling. Their involvement in blood pressure regulation via epithelial sodium channel modulation and their facilitative role in HIV-1 entry further underscore their clinical significance. These multifaceted functions position P2Y₂ receptors as promising therapeutic targets for diverse diseases, warranting further investigation for translational applications. Full article

Background: Type 2 diabetes mellitus (DM) is a major cardiovascular risk factor that induces monocyte dysfunction and contributes to their accumulation in atherosclerotic lesions. Monocyte recruitment and accumulation in the tissues contribute to chronic inflammation and are essential to the pathobiology of diabetes-induced atherosclerosis. However, the mechanisms that drive the accumulation of monocytes in the diabetic environment are not clearly understood. Methods: Primary monocytes from type 2 (T2) DM and non-T2DM individuals were isolated using magnet-assisted cell sorting. To examine the influence of a diabetic milieu on monocyte function, monocytes from T2DM patients, db/db mice, or human monocytes subjected to hyperglycaemia were analysed for their responses to pro-atherogenic cytokines using Boyden chamber assays. Furthermore, the interactions of non-diabetic and diabetic monocytes with TNFα-inflamed endothelium were studied using live-cell imaging under physiological flow conditions. RT-qPCR and FACS were used to study the expression of relevant molecules involved in monocyte-endothelium interaction. Results: CD14⁺CD16⁻ monocytes isolated from T2DM patients or monocytes exposed to hyperglycaemic conditions showed reduced chemotactic responses towards atherosclerosis-promoting cytokines, CCL2 and CX3CL1, indicating monocyte dysfunction. Under flow conditions, the transendothelial migration (TEM) capacity of T2DM monocytes was significantly reduced. Even though these monocytes adhered to the endothelial monolayer, only a few transmigrated. Interestingly, the T2DM monocytes and monocytes exposed to hyperglycaemic conditions accumulated in the ablumen following transendothelial migration. The time period in the ablumen of T2DM cells was prolonged, as there was a significant impairment of the reverse transendothelial migration (rTEM). Mechanistically, the T2DM milieu specifically induced the activation of monocyte integrins, Macrophage-1 antigen (Mac-1; integrin αMβ2 consisting of CD11b and CD18), and Lymphocyte function-associated antigen 1 (LFA-1; αLβ2 consisting of CD11a and CD18). Furthermore, elevated levels of CD18 transcripts were detected in T2DM monocytes. Junctional Adhesion Molecule 3 (JAM-3)–MAC-1 interactions are known to impede rTEM and T2DM milieu-potentiated JAM-3 expression in human coronary artery endothelial cells (HCAEC). Finally, the overexpression of JAM-3 on HCAEC was sufficient to completely recapitulate the impaired rTEM phenotype. Conclusions: Our results revealed for the first time that the enhanced T2DM monocyte accumulation in the ablumen is not secondary to the elevated transmigration through the endothelium. Instead, the accumulation of monocytes is due to the direct consequence of a dysfunctional rTEM, potentially due to enhanced JAM3-MAC1 engagement. Our results highlight the importance of restoring the rTEM capacity of monocytes to reduce monocyte accumulation-dependent inflammation induction and atherogenesis in the T2DM environment. Full article