Search Results (20,536)

Theaflavin-3,3′-digallate (TF3), a flavan-3-ol derivative found in black tea, exhibits anti-tumor activity, but its mechanism of action in hepatocellular carcinoma (HCC) remains to be elucidated. Here we systematically delineate how TF3 targets Pin1 to suppress HCC through an integrated approach combining computational simulations, enzyme assay and cell-based assays. TF3 spontaneously occupies the active site of Pin1 with a docking score of −8.9 kcal/mol, inhibiting its PPIase activity (IC₅₀ = 60.33 μmol/L) and yielding a binding constant (K_a) of 3.1 × 10⁵ mol/L. Drug affinity responsive target stability (DARTS) assays further corroborated that TF3 directly engages Pin1 within HCC cells. Functionally, TF3 potently suppressed the viability of HepG2, SK-Hep-1 and Huh-7 cells in both dose- and time-dependent manners (IC₅₀ = 61.22, 14.09 and 69.85 μmol/L at 24 h, respectively), and exhibited a modest selectivity window against the viability of L02 and THLE-2 cells (IC₅₀ = 133.43 and 90.29 μmol/L at 24 h, respectively). In addition, TF3 triggers mitochondrial-mediated apoptosis, evidenced by ROS accumulation, loss of mitochondrial membrane potential, an elevated Bax/Bcl-2 ratio, cytochrome c release and enhanced PARP cleavage, and induces G₂/M phase arrest. It also robustly inhibits HCC cell proliferation, invasion and migration, coinciding with downregulation of proteins governing cell cycle progression and invasive behavior. Transcriptome profiling coupled with enrichment analysis discovered that TF3 treatment differentially regulated 5009 genes, which were prominently enriched in pathways linked to apoptosis, cell cycle control, MAPK and PI3K/AKT signaling pathways. Western blotting analysis revealed that TF3 selectively suppresses phosphorylation of p38 and the PI3K/AKT cascade, activating JNK phosphorylation. In summary, our findings indicate that TF3 suppresses HCC proliferation by targeting Pin1, with attendant modulation of the MAPK and PI3K/AKT pathways, thereby presenting a potential candidate for targeted HCC therapy. Full article

Background/Objectives: Sleep is critical for young adults, particularly those with type 1 diabetes (T1D), who face unique challenges in achieving recommended sleep and diabetes health targets. The purpose of this study guided by the theoretical framework of self-regulation theory is to explore how these individuals navigate self-regulatory processes in their sleep behaviors through mechanisms of self-monitoring, self-judgment, and self-evaluation. Methods: A qualitative descriptive design was implemented using semi-structured interviews with 34 young adults (ages 18–30) living with T1D. Data were collected through focused interviews, sleep diaries, actigraphy, and continuous glucose monitoring, followed by thematic analysis to identify sleep behavior self-regulation patterns. Results: Three primary themes were identified: (1) Sleep Behavior Self-Monitoring—highlighting participants’ awareness of their sleep habits and the diabetes-related impacts on these habits; (2) Sleep Behavior Self-Judgment—reflecting how personal and societal standards inform their evaluation of sleep health; (3) Sleep Behavior Self-Evaluation—showing emotional responses associated with sleep out-comes, where good sleep led to positive feelings and motivation, while poor sleep resulted in frustration. Conclusions: Understanding sleep behavior self-regulation among young adults with T1D is crucial for improving sleep health and diabetes management. Targeted interventions incorporating sleep education and self-regulatory strategies may enhance both perceived sleep quality and overall well-being in this population. Full article

Based on the stimulus–organism–response (S–O–R) framework, this study explored the psychological spillover mechanism through which tourism experiences in Museum Agglomeration Areas (MAAs) enhance city image and influence behavioral intentions. Structural equation modeling (SEM) based on survey data yielded several key findings. First, information visibility, content visibility, and the quality of amenities and the operational environment played critical roles in shaping tourists’ internal states, including perceived experiential value, affective response, immersion, and satisfaction. In addition, the social atmosphere emerged as an important factor in enriching these evaluations. Second, accessibility and connectivity were identified as factors that reduce friction along the visitor journey, thereby enhancing experiential continuity and immersion. Third, experiential value and immersion were found to be the primary mediators among the internal-state variables, transmitting the effects of environmental stimuli to city-level perceptions and behavioral intentions, such as revisit and recommendation intentions. These findings suggest that the competitiveness of MAAs lies not merely in spatial agglomeration itself but also in their ability to provide engaging and meaningful content, maintain safe and enjoyable operational environments, and develop integrated circulation and information systems. By conceptualizing MAAs as sites of district-scale tourism experiences, this study extends the application of the S–O–R framework to a multi-site urban cultural context and clarifies how differentiated internal states mediate the spillover from district experience to city-level perceptions and behavioral intentions. Rather than proposing a fundamentally new theoretical framework, the study offers a context-specific refinement of the organism layer and provides empirically grounded implications for design and operational strategies in culturally clustered urban districts. Full article

Dysregulation of microRNA expression in breast cancer (BC) has been associated with molecular disturbances involved in cancer initiation, progression and metastasis. Specific microRNAs also act as endocrine modulators in BC, thereby influencing the biological behavior of the tumor and drug responses. Our objective was to employ bioinformatics tools to identify and characterize microRNAs acting as candidate players involved in epithelial–mesenchymal transition, migration, invasion, and/or hormonal regulation in BC. We systematically integrated microRNA profiling data from three different studies on BC cell lines with different invasive capabilities and from another study on lymph node metastases and matching primary BC, resulting in five microRNA hits—DE-microRNAs miR-146a-5p, miR-222-3p, miR-205-5p, miR-141-3p and miR-200c-3p. This set of microRNAs was evaluated for clinical significance in BC and subjected to target prediction, microRNA–mRNA network construction, functional enrichment analysis and quantification in BC cell lines by qPCR. An upregulated DE-microRNA, miR-222-3p, displayed distinctive pro-metastatic features, supported by its clinical relevance, as well as by the results of the functional enrichment analysis of its target genes. Downregulation of the members of the miR-200 family and miR-205-5p were significantly associated with negative clinical features, while their targets were enriched with genes that were relevant to cancer aggressiveness. These results are in line with the presumed functional relevance of the selected DE-microRNAs in BC. Full article

Attitudes towards animal welfare depend on people’s lifestyles and education levels, yet little is known about the attitudes of nomadic people. We distributed a questionnaire and collected 1660 valid responses, representing individuals with or without nomadic connections and varying education levels and genders. We used ordinal logistic regression to analyze the impact of these two factors on perceptions, attitudes, and behavioral intentions related to animal welfare. Women and those with higher education levels tended to hold more positive attitudes toward animal welfare, but for farm animals, this was only extended to common female reproducing animals, such as cows, sheep, goats, and laying hens, but not other farm animals, such as beef cattle and broiler chickens. This may reflect a greater sensitivity towards reproducing animals. The influence of nomadic connections on attitudes towards animal welfare was not linear—respondents with nomadic connections themselves or family members of the same generation generally had more negative attitudes, while those with grandparents with nomadic connections had more positive attitudes on several animal welfare issues. This may reflect a generational change in the attitudes of nomadic people towards animals. Full article

Constant composition expansion (CCE) experiments provide critical relative-volume and density information describing the thermodynamic behavior of reservoir oils and gases under varying pressure. These properties are vital inputs for hydrocarbon reservoir engineering, as they impact how oil and gas move through the reservoir during production. However, the need for specialized personnel, high-end equipment and measures taken to ensure safety in handling high pressure fluids often render the CCE experiments expensive and slow. This work introduces a Local Interpolation Method (LIM), a proximity-informed, end-to-end CCE fluid properties prediction Artificial Intelligence (AI) model that leverages domain expertise and synthetic Pressure–Volume–Temperature (PVT) data archives that mimics the actual data. The AI model generates surrogate CCE behavior for new fluids, thereby reducing the need for completing laboratory CCE measurements when sufficiently similar fluids exist in the available archive and neighborhood support is strong. Each new fluid is embedded in a compositional–thermodynamic descriptor space, and its response is inferred from a small neighborhood of thermodynamically similar fluids. Within this locality, the LIM combines hybrid local interpolation for key scalar properties (such as saturation-point quantities and expansion endpoints) with shape-preserving reconstruction of monophasic and diphasic relative-volume curves, enforcing continuity at saturation and consistency between relative volume, density and compressibility. The workflow operates purely at inference time and does not require case-specific retraining. Application to a curated archive of CCE tests shows that LIM reproduces key CCE features with very good agreement to existing data across a range of fluid types, indicating that proximity-based AI modeling can substantially reduce reliance on new CCE experiments while maintaining engineering-useful agreement for compositional simulation workflows. Under leave-one-out evaluation on 488 CCE tests, mean curve-level Mean Absolute Percentage Error (MAPE) is 0.07% for monophasic relative volume and 0.07% for monophasic density. For well-supported neighborhoods (Tiers 1–3, n = 376), mean MAPE is 0.04% for both, with 2.65% for derived compressibility and 1.78% for diphasic relative volume. The workflow is automated in software to facilitate reproducible inference on operator-owned archives and can reduce turnaround time and laboratory burden in well-supported neighborhoods. The proposed AI model uses available experimental data owned by each operator and does not use others’ data while respecting the data privacy and data ownership. Full article

In earthquake engineering and hydraulic engineering, the dynamic mechanical behavior of cohesive soils is crucial to ensure structural stability. However, most existing dynamic constitutive models fail to adequately account for the influence of strain history, which is essential for accurately predicting soil behavior under seismic loading. This study conducted a series of cyclic single-shear tests on both in situ and disturbed Changsha cohesive soils. Hysteresis curves were obtained under varying shear strain amplitudes to investigate the degradation patterns of the dynamic shear modulus and the evolution of the damping ratio. Furthermore, multi-cycle loading tests under constant strain amplitude were carried out to clarify the correlation between damping ratio, dynamic shear modulus, and the number of loading cycles. A simplified practical dynamic model, applicable to general cohesive soils, is proposed. This model incorporates the effect of strain history and provides a valuable reference for analyzing the dynamic response of soils subjected to earthquake actions. Full article

Ca²⁺-rich brines strongly destabilize bentonite-based drilling fluids by weakening hydration and increasing filter-cake permeability. In this work, raw sodium bentonite (Na-Bt) and a series of cation-exchanged bentonites (Li-, Mg-, Ca-, and K-Bt) were comparatively investigated to clarify how cation-dependent hydration characteristics and interlayer structure govern filtration behavior under saline conditions. XRD, zeta potential, TG–DTG, BET, and SEM were employed to correlate basal spacing, surface electrostatic properties, thermal/water-loss behavior, surface area and pore-structure characteristics, and filter-cake microstructure with API fluid loss. Among the examined 2 wt% brines, CaCl₂ produced the most severe deterioration and was therefore selected as the representative screening condition. Under 2 wt% CaCl₂, Li-Bt exhibited the lowest FL_API (141 mL), which was substantially lower than that of Na-Bt (265 mL), indicating the most favorable intrinsic resistance to Ca²⁺-dominated salinity. The cation-exchange analysis further showed that Li-Bt and Mg-Bt had relatively higher calculated exchange degrees than Ca-Bt and K-Bt under the present preparation conditions. Based on the 2 wt% CaCl₂ dataset, a descriptor-based relation between FL_API, hydrated ionic radius (r_h), and basal spacing (d₀₀₁) was established, and an Al-modified bentonite provided an out-of-sample verification with close agreement between predicted and measured filtration loss. Additional tests in 1–3 wt% CaCl₂ showed that although absolute fluid loss increased with brine severity, the relative ranking of the cation-exchanged bentonites remained broadly unchanged. TG–DTG, BET, and SEM results further provided complementary evidence for the structural and microstructural differences among the samples. Overall, the results demonstrate that hydration-related response, interlayer structure, and surface/pore characteristics jointly govern the filtration behavior of cation-exchanged bentonites, providing a useful basis for screening salt-tolerant clay materials for Ca²⁺-rich brines. Full article

Understanding how Bitcoin mining is distributed across countries is important for evaluating both the sustainability and resilience of the network. In this study, we examine the evolution of total Bitcoin electricity consumption alongside the geographic distribution of Bitcoin mining. Data are provided by the Cambridge Centre for Alternative Finance (Licensed under CC BY–NC–SA 4.0): Annual data from the Cambridge Bitcoin Electricity Consumption Index (2010–2025) and a monthly panel of country-level Bitcoin hashrate shares for 105 countries (September 2019–January 2022). To assess the degree of decentralization in the global mining network, we employ entropy-based measures, inequality indices, and panel convergence tests. The results indicate that total electricity consumption grew exponentially during the early years of Bitcoin, but later transitioned to a more stable and approximately linear path. Country-level permutation entropy reveals highly volatile and dynamic mining trajectories. The Theil index shows that cross-sectional inequality declines over time, while increasing symbolic entropy reflects a progressively more even cross-country distribution of mining activity. Further evidence from $\sigma$-convergence supports a statistically significant reduction in cross-country dispersion of mining shares. Dynamic panel fixed-effects estimates reveal mean-reverting behavior in relative country shares, consistent with stochastic convergence. Finally, Phillips–Sul analysis points to heterogeneous early transition paths but ultimately supports convergence toward a single global club. The gradual geographical decentralization occurs alongside persistent core–periphery asymmetries in long-run mining shares. Overall, our findings suggest that Bitcoin mining behaves as a globally integrated industry in which computational capacity reallocates rapidly across countries in response to economic and regulatory conditions. Full article

This bibliometric study examines the role of ubiquitous computing and intelligent systems in the treatment of mental and neurological disorders. Ubiquitous computing integrates computational intelligence into everyday environments, enabling seamless monitoring and support of patients. Intelligent systems, including wearable devices, environmental sensors, and mobile health applications, collect real-time data on behavior, physiology, and environmental factors. These systems support early detection of symptom changes, adherence to treatment, and crisis prediction through context-aware analysis. Artificial intelligence (AI) processes the collected data to generate personalized therapeutic feedback and notify healthcare providers when intervention is needed. In mental health care, intelligent environments can monitor mood, sleep, and social interaction patterns, providing valuable objective information about mental health status. In the case of neurological conditions such as Parkinson’s disease or epilepsy, intelligent systems facilitate movement tracking, seizure detection, and cognitive assessment outside of the clinical setting. Integration with electronic health records and telemedicine platforms ensures coordinated and responsive care. Ethical design, privacy protection, and patient consent remain key to successful implementation. In this way, ubiquitous computing is transforming care models by increasing autonomy, precision, and continuity in the treatment of complex neurodegenerative diseases, including those related to neurodegeneration in aging. Full article

Islanded photovoltaic microgrids with limited inertial support can undergo steep frequency excursions after sudden generation loss or abrupt load changes. This paper develops and evaluates a synthetic inertia strategy supported by a supercapacitor energy storage unit for fast frequency containment in this type of system. The proposed approach commands rapid active-power injection or absorption from the measured rate of change of frequency, thereby emulating the immediate inertial contribution usually associated with rotating machines while preserving a simple and physically interpretable control structure. The supercapacitor is represented through a resistance–capacitance model that includes equivalent series resistance and is interfaced through a bidirectional buck–boost power converter subject to practical current, voltage, and power limits. Rather than claiming a fundamentally new storage-support concept, the contribution of this paper lies in providing a transparent and constraint-consistent benchmark that integrates measured operating profiles, explicit supercapacitor limits, hybrid frequency–RoCoF support, and stress-aware comparative assessment under a common set of plant assumptions. The methodology is assessed in time-domain simulations under representative benchmark disturbances, including an approximately ten percent photovoltaic generation loss, a ten percent load increase, and a combined event. Performance is evaluated through the peak rate of change of frequency, frequency nadir, integral error indices, time outside the admissible band, and supercapacitor stress indicators such as current peaks, voltage depletion, and energy throughput. An additional non-ideal assessment is also included to examine the behavior of the RoCoF-based support law under bounded frequency-measurement perturbations and delayed control action. A complementary variability-driven case based on a highly fluctuating measured irradiance window is also used to examine the behavior of the adaptive energy-management mechanism under repeated photovoltaic-power variations. A local small-signal analysis is also included to show that the selected gain region is dynamically plausible in the unsaturated regime. The results show that the proposed adaptive hybrid strategy improves the overall frequency response while maintaining admissible supercapacitor operation, thus providing a stronger methodological basis for rapid frequency support in islanded photovoltaic microgrids. Full article

Men who have used violence against intimate partners remain an under-researched population, despite their potential to advance understanding of motivations and relational dynamics underlying such behavior. This study employed semi-structured interviews and interpretative phenomenological analysis to examine the lived experiences of five adult men with histories of partner violence. A superordinate theme, Chaotic Interpersonal and Systemic Relationships, encompassed five experiential themes describing volatile partnerships shaped by mutual vulnerabilities. Participants commonly reported trauma histories and/or antisocial traits influencing partner selection, with abuse experienced as bidirectional. Disillusionment emerged when participants perceived that the mutual nature of violence was unacknowledged, limiting their engagement in meaningful change. Although behavior change programs were often understood at a conceptual level, participants struggled to translate insight into sustained behavioral transformation. Consistent with post-traumatic growth theory, participants described developing greater personal responsibility and more constructive views of relationships over time. Greater systemic recognition of bidirectional violence, identified in the literature as a prevalent form of intimate partner violence, may strengthen the therapeutic alliance and support more nuanced etiological inquiry. Shifting systemic responses from deficit-based, gendered models toward strength-based approaches may better harness men’s capacity for more permanent positive psychological and behavioral change. Full article

This paper investigates the mechanical transfer mechanism of bimetallic composite pipes used in highly sour gas fields located in high-steep mountainous areas. It systematically analyzes the mechanical response behavior of these pipes under the coupled effects of complex geological conditions and operational loads. By establishing and validating a finite element model that accounts for material nonlinearity and pipe–soil interaction, the study examines the influence of key factors—including internal pressure, landslide displacement, and base pipe wall thickness—on the stress distribution and transfer mechanism within the pipeline. The results demonstrate that increased internal pressure significantly elevates both circumferential and axial stresses: when internal pressure increases from 7 MPa to 9 MPa, the liner hoop stress increases by 35.5% and the base pipe axial stress increases by 27.5%. When landslide displacement exceeds a critical threshold of 3 m, the stress in the base pipe rises sharply, with axial stress increasing by 39.7% when displacement increases from 3 m to 5 m; conversely, increasing the base pipe wall thickness from 12 mm to 15 mm effectively reduces the overall stress level, decreasing base pipe axial stress by 40.4% and liner axial stress by 86.9%. Stress transfer exhibits a dual-path characteristic, which can be described as “bidirectional transfer induced by internal pressure” and “progressive transfer caused by landslide”. These quantitative findings provide a theoretical basis for the safe design and operation of bimetallic composite pipes in high-steep mountainous regions. Full article

Seismic design methods often involve high construction costs and may lead to severe structural damage during strong earthquakes. Energy dissipation technology represents an efficient approach to improving seismic performance through the integration of devices that absorb and dissipate induced seismic energy. This study investigates the seismic behavior of a five-story mixed-use hotel building with and without viscous fluid dampers through advanced numerical modeling using ETABS software, applying static, dynamic, and time-history analyses and considering representative seismic records from Ica, Peru. The research follows an applied and quantitative approach, in which two structural configurations were modeled to evaluate the efficiency of energy dissipation systems in mitigating seismic effects. The results demonstrate that the incorporation of viscous fluid dampers reduced maximum displacements by 51.12% and interstory drifts by 52.82% along the X–X axis, while absorbing approximately 74% of the induced seismic energy. All structural responses remained within safe performance limits. The findings confirm that viscous dampers substantially enhance structural seismic performance by increasing safety and functionality, and they validate their applicability as an efficient and reliable alternative for mid-rise buildings located in high-seismicity regions. Full article

Electronic word of mouth (eWOM) and traditional word of mouth (WOM-T) are key information channels in consumer decisions, but there are still gaps in integrative models that analyze both channels simultaneously in emerging contexts. This exploratory, theory-informed study proposes a conceptual model that articulates five antecedents—satisfaction, trust, emotional bond, openness to novelty, and perceived social influence—two mediators—consumer engagement and recommendation intention—and two outcome behaviors—eWOM and traditional WOM—to examine how these variables are associated with the generation of recommendations among young/internet-connected consumers of SME services in the Lambayeque Region, Peru. Using PLS-SEM with 380 participants, 25 structural hypotheses were evaluated, including direct effects and simple and sequential mediations. In this non-probability sample, the hypothesized associations were statistically supported: antecedents were positively associated with engagement, which was positively associated with recommendation intention, which in turn predicted both online and offline WOM behaviors. Emotional bond and trust showed particularly strong effects. The model explained between 49% and 64% of the variance in endogenous variables. The findings contribute to understanding word-of-mouth dynamics in emerging markets for the studied segment of digitally connected consumers, with implications for relational marketing strategies and SDGs 8 and 12. Importantly, the contribution to SDG 12 is conditional: word-of-mouth can also amplify unsustainable consumption when recommendations are not linked to responsible practices; this caveat should be considered when interpreting the sustainability implications of these findings. Full article