Search Results (11,493)

This work examines the machining responses of dry turning in ultrasonic-assisted stir-squeeze cast A356 hybrid nanocomposites reinforced with zirconia (ZrO₂) and graphene oxide (GO). Accordingly, flank wear (VBc) ranged from 0.061 to 0.238 mm, influenced by abrasion, adhesion, built-up edge (BUE) formation, and diffusion mechanisms. Cutting speed had the most significant effect on flank wear (65.65%), followed by depth of cut (18.2%) and feed rate (11.13%), supported by a well-fitted regression model (R² = 0.987; p < 0.05). Surface roughness (Ra) ranged from 1.733 to 7.012 μm, with cutting speed, feed rate, and depth of cut contributing 70.42%, 15.43%, and 9.56%, respectively. The cutting temperature was limited to 127 °C, primarily influenced by cutting speed (60.68%), whereas cutting power varied between 0.353 and 0.644 kW, mainly governed by cutting speed (68.71%) and depth of cut (25.92%). The chip morphology showed a segmented sawtooth pattern due to cyclic fracture initiation during material removal. Multi-criteria optimization using complex proportional assessment (COPRAS) identified v = 90 m/min, f = 0.06 mm/rev, and d = 0.1 mm as the optimal parameters, yielding a tool life of 22.6 min and a machining cost of INR 58.69 per item. This research is further focused on the implementation of different cooling lubrication techniques utilizing environmentally friendly cutting fluids, including Minimum-Quantity Lubrication and nano-MQL, among other types of environments. Full article

The significant CO₂ emissions from cement manufacturing and overuse of natural aggregates, especially river sand mining, have been a global environmental concern for decades. This is a review study that aimed to evaluate the solution by reviewing past studies on the incorporation of supplementary cementitious materials (SCMs) and recycled aggregates (RAs) to produce sustainable concrete (SC). Regarding environmental consequences, the results highlighted that the cement industry accounts for a 5–8% carbon footprint. Concurrently, the demand for high-quality river sand has escalated, leading to widespread river degradation, altered channel morphology, and effects on river ecosystems. Past studies’ experimental results indicate that silica fume (SF), as an effective SCM, enhances the strength and durability of sustainable concrete to its optimal levels. However, the higher RA content resulted in reductions in engineering properties. The published studies also reported that lower percentages of SF combined with RAs had a positive effect on the strength and durability of design mix concrete, thereby further strengthening the findings of this review. This factor was found to be missing in most studies. A cost–benefit analysis for combined SCMs and RAs was introduced in this study. This review study evaluated the cost–benefit analysis of 1 m³ of sustainable concrete. The highest benefit was observed at 20.97% in a study when optimized 10%SF + 100 RAs were combined. It showed that the combined use of SCMs with RAs at optimal levels satisfied the strength and durability requirements. In addition, the benefits of sustainable concrete were achieved without any cost increase, a new outcome revealed by this review. Full article

Background/Objectives: Adolescent mental health problems have increased in recent years, with growing concern about the impact of digital behaviors such as problematic video game use and gambling. Internet Gaming Disorder (IGD) and Problem Gambling Symptoms may share psychological risk markers, but evidence in Spanish adolescents is limited. This study aimed to examine the relationship between IGD, problem gambling symptoms, and mental health, and to identify sociodemographic, psychological, and behavioral factors associated, including microtransactions and loot boxes. Methods: A cross-sectional study was conducted with secondary education students from Extremadura (Spain). The final sample included 343 participants. Measures included an ad hoc questionnaire on video game use, the IGDS9-SF, SOGS-RA, and the Strengths and Difficulties Questionnaire (SDQ). Descriptive analyses, Spearman correlations, and multivariable regression (Poisson and negative binomial) were performed. Results: IGD and gambling were positively correlated (Spearman’s ρ = 0.386, p < 0.001) and associated with higher mental health difficulty scores (IGD: ρ = 0.299, p < 0.001; gambling: ρ = 0.214, p < 0.001). Male gender was associated with both outcomes (IGD: incidence rate ratio [IRR] = 1.21 [95% Confidence Interval: 1.13–1.30]; gambling: IRR = 2.90 [1.85–4.60]). Microtransactions were associated with both behaviors (IGD: IRR = 1.17 [1.09–1.25]; gambling: IRR = 1.74 [1.19–2.54]), while loot box use was related only to IGD (IRR = 1.13 [1.05–1.21]). Total SDQ score was positively associated with both IGD (IRR = 1.02 [1.02–1.03]) and gambling (IRR = 1.10 [1.06–1.13]). Younger age was associated with higher IGD scores (IRR = 0.97 [0.96–0.99]). Conclusions: There are similarities in the associations among the examined factors and increased scores of IGD and gambling in adolescents, particularly male gender, higher mental health difficulties scores, and involvement in monetized gaming systems. School-based, family, and public health prevention strategies may benefit from addressing the importance of psychological well-being and increase awareness of the potential risks associated with digital gaming practices. Full article

For decades RAS mutations represented a chimera for drug developers, as all efforts put into attempting to pharmacologically inhibit them failed. Finally, in recent years, the advent of the KRAS G12C inhibitors sotorasib and adagrasib pushed the development of several new drugs; therefore, the landscape of RAS inhibitors evolved and now includes several compounds with different mechanisms of action. In this review we provide an updated summary of RAS inhibitor drugs, detailing their mechanism of action, pharmacokinetics and toxicity profile as well as efficacy studies. Full article

Chronic liver disease (CLD) constitutes a major global health burden, with high morbidity and mortality, limited treatment options for several etiologies, and an urgent need for novel therapeutic targets. Fibroblast growth factor 1 (FGF1) is a unique member of the FGF family capable of binding all four FGFR subtypes, thereby regulating multiple signaling pathways including PI3K/AKT, Ras/MAPK, and PLCγ, which are involved in metabolism, cell survival, proliferation, and tissue repair. Emerging evidence highlights the multifaceted and context-dependent roles of FGF1 in CLD. In drug-induced liver injury (DILI) caused by anti-tuberculosis drugs, acetaminophen, or doxorubicin, FGF1 confers protection by restoring bile acid homeostasis, reducing oxidative stress, inflammation, and apoptosis. In Metabolic dysfunction-associated steatotic liver disease (MASLD), FGF1 ameliorates hepatic steatosis, oxidative injury, and insulin resistance through downregulation of SREBP1, upregulation of PPARα, and activation of Nrf2-mediated antioxidant responses. Conversely, in primary sclerosing cholangitis (PSC), FGF1 aggravates ductular reaction, biliary senescence, and liver fibrosis via upregulation of SASP and TGF-β1, suggesting that inhibition of the FGF1/FGFR axis may be therapeutic. For alcohol-related liver disease (ALD), although direct experimental evidence is lacking, FGF1 is hypothesized to confer protection given its known activities against oxidative stress, lipid dysregulation, and cell death. Despite its promise, the mitogenic potential of FGF1 raises safety concerns; however, N-terminally modified FGF1 analogs (e.g., FGF1Δ) retain metabolic benefits with reduced proliferative activity. Collectively, FGF1 represents a versatile and disease-dependent regulator in CLD, warranting further mechanistic studies, safety evaluations, and development of targeted analogs as a novel therapeutic strategy for difficult-to-treat liver diseases. Full article

Remote sensing change detection (RSCD) aims to produce pixel-accurate change maps from bi-temporal images yet is fundamentally challenged by radiometric pseudo-changes (season, illumination, and atmosphere) that cause structure–environment entanglement in deep features. We propose CSD-Net, a framework centered on content–style decoupling (CSD): a physics-inspired feature decomposition mechanism that encourages separation between intrinsic geometric content and extrinsic environmental style. In the CSD module, learnable pseudo-change tokens estimate a spatially invariant global style proxy through cross-attention and broadcast, and subtraction performs feature-level radiometric-bias compensation, yielding pseudo-change-robust content features for change prediction. CSD-Net (Base) alone achieves state-of-the-art performance across four benchmarks (LEVIR-CD, LEVIR-CD+, CDD, and WHU) with favorable accuracy–efficiency trade-off (14.49M parameters and 15.26G FLOPs). We further explore an optional extension, CSD-Net⁺, that employs an MLLM (Qwen2.5-3B, LoRA-tuned) as a semantic refiner and SAM for instance mask refinement, coupled with uncertainty-aware three-way softmax fusion. This exploratory Stage 2 brings modest but consistent IoU improvements of 0.45–2.20% at the cost of significant computational overhead and is designed for offline, quality-critical scenarios. We provide a comprehensive account of both the effectiveness and the limitations of the proposed approach, including the marginal benefit–cost ratio of foundation model integration. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) accumulation and a breakdown of mitochondrial homeostasis. Vitamin K2 (VK2) has emerged as a potential neuroprotective agent, yet the specific molecular cascades linking its intervention to the restoration of mitochondrial integrity remain poorly understood. This study utilizes an AD Drosophila model to investigate the efficacy of VK2 and elucidates its multidimensional regulatory mechanisms. Behavioral analysis showed that VK2 significantly rescued locomotor impairments, improving both vertical climbing and horizontal walking performance. Crucially, VK2 intervention achieved a systemic rescue of mitochondrial health: transmission electron microscopy (TEM) confirmed the preservation of mitochondrial ultrastructure and cristae density, while biochemical assays demonstrated a robust recovery of bioenergetic markers, including ATP levels and the NAD⁺/NADH ratio. Furthermore, VK2 treatment stabilized the mitochondrial membrane potential (MMP) and effectively attenuated the accumulation of reactive oxygen species (ROS). To identify the molecular drivers of this recovery, an unbiased integration of human clinical transcriptomic data and network pharmacology prioritized the EGFR-Ras-ERK signaling axis as a central hub. In vivo validation confirmed that VK2 suppresses the pathological overactivation of this cascade. VK2 reduced EGFR phosphorylation in parallel with the effects observed for the EGFR inhibitor Gefitinib. Collectively, our findings show that VK2 ameliorates locomotor deficits and mitochondrial dysfunction in Aβ42-expressing flies and that these effects are associated with suppression of the EGFR-Ras-ERK signaling axis. Further studies are required to establish direct target engagement and pathway causality. Full article

Nectin-4 has emerged as a clinically relevant target in muscle-invasive bladder cancer (MIBC), primarily because of its role in antibody–drug conjugate-based therapies. However, the broader biological context of Nectin-4 expression and its association with tumor-promoting signaling pathways in MIBC remain insufficiently characterized. In this single-institution study, Nectin-4 expression (H-score 0–300) was assessed by immunohistochemistry in two independent MIBC cohorts. Associations between Nectin-4 expression and key markers related to growth signaling, metabolic regulation, and inflammation were analyzed alongside clinicopathological characteristics. Nectin-4 expression was significantly higher in malignant tissue than in non-malignant tissue (p = 0.0016 and p = 0.0302, respectively). Nectin-4 expression was not associated with demographic or clinicopathological parameters; however, a trend toward lower expression in more advanced disease stages was observed. Significant positive correlations were identified between Nectin-4 expression and protein kinase B (p = 0.0004), cytoplasmic (p = 0.0115) and membranous somatostatin receptor 2 (p = 0.0125), insulin receptor substrate 1 (p = 0.03), and interleukin-1 receptor antagonist (IL-1RA; p = 0.0045). In contrast, a negative correlation was observed with the IL-1β/IL-1RA ratio (p = 0.0246). Although Nectin-4 expression was not significantly associated with cancer-specific or overall survival, a trend toward shorter relapse-free survival was observed in patients with lower Nectin-4 expression (p = 0.0531). In multivariate analysis, patient age, but not Nectin-4 expression, emerged as an independent prognostic factor. Although Nectin-4 expression does not appear to have independent prognostic value, its biological associations suggest that it reflects an integrated tumor-related signaling context. These findings support further investigation of Nectin-4 as part of rational, biology-driven therapeutic strategies in bladder cancer. Full article

Orbital atherectomy (OA) is a highly effective atherectomy device used to treat heavily calcified coronary arteries. The technique for using OA is critical and depends on appropriate use of the dedicated guidewire. OA employs a centrifugal, differential sanding mechanism with bidirectional movement. When used with proper technique, the device appears to be associated with a low rate of complications, such as bradycardia and slow flow, compared with rotational atherectomy (RA), and results in high procedural success rates. We describe our experience with the OA device and procedural techniques in our catheterization laboratory. Full article

To address surface quality defects caused by traditional mechanical polishing of gears, such as machining scratches and large surface waviness, this study proposes a novel immersed chemical-mechanical polishing (CMP) process for gear finishing. Numerical simulations were conducted in FLUENT to analyze the gear surface stress distribution and polishing fluid flow trajectories under different process conditions. The Euler–Euler method and RNG k–ε turbulence model were used to optimize process parameters and clarify the formation mechanism of ultra-smooth tooth surfaces. Experimental results for spiral bevel gears show that the proposed immersed CMP process effectively improves surface quality. The tooth profile roughness was reduced from Ra 1.531 μm to 0.509 μm, and surface scratches were significantly alleviated. These results confirm the feasibility and effectiveness of the proposed process. This study provides a reliable approach for efficient and precision polishing of complex-structured gears and extends the application of CMP technology to non-planar mechanical components. Full article

Network intrusion detection systems (NIDS) play a crucial role in modern network environments where diverse and rapidly evolving traffic patterns are observed. Although deep learning-based NIDS have demonstrated strong performance within specific datasets, their effectiveness significantly degrades when applied to unseen network environments due to domain discrepancies. In this paper, we first experimentally demonstrate the performance degradation of time-series-based NIDS under cross-domain conditions using multiple benchmark datasets. Then, we propose a LoRA-based domain adaptation framework for time-series-based NIDS models. Instead of retraining the entire model, the proposed approach freezes the backbone network and applies low-rank updates to selected layers, enabling parameter-efficient adaptation to new domains. Experimental results show that the proposed method consistently improves cross-domain detection performance across multiple dataset combinations, particularly in terms of recall, while requiring only a small number of additional parameters. Full article

Cancer is a genetic disease driven by the accumulation of mutations that disrupt normal cellular growth. Among the most frequently mutated families are protein kinases, inositol polyphosphate kinases, and GTPases, which together function as central molecular switches controlling proliferation, survival, and metabolism. In cancer, activating mutations in protein kinases, such as EGFR and BRAF, lead to uncontrolled downstream signaling by locking these enzymes in a constitutively active state. Similarly, mutations affecting inositol kinases, notably PI3KCA, hyperactivate the PI3K/AKT pathway, promoting relentless cell survival and resistance to apoptosis. GTPases, particularly Ras family members (KRAS, NRAS, HRAS), are classical oncogenes where single amino acid substitutions impair their intrinsic GTP hydrolysis activity, trapping them in a persistently GTP-bound “on” state. This unleashes continuous mitogenic signaling independently of external growth factors. Collectively, these mutations are not random but converge on a limited set of core pathways, making them key drivers of tumor initiation and progression. Understanding the specific molecular consequences of kinase and GTPase mutations has directly informed the development of targeted therapies, including small molecule inhibitors and monoclonal antibodies, now used in routine clinical practice. Full article

²¹²Pb is an important medical radionuclide for targeted alpha therapy, and its reliable supply depends on the efficient production of parent nuclides such as ²²⁸Ra, ²²⁸Th, and ²²⁴Ra. Natural thorium resources are abundant and represent a potential source of these radionuclides. However, the separation and enrichment of trace radium from thorium-rich high-salinity systems remain challenging due to extremely low radium concentrations and Th/Ra mass ratios on the order of 10⁹. In this work, a radium separation strategy based on BaSO₄ co-precipitation was developed. The precipitation behavior of BaSO₄, precipitation kinetics, radium co-precipitation efficiency, and thorium recovery in concentrated thorium nitrate solutions were systematically investigated. The results show that elevated ionic strength and competitive interactions between Th⁴⁺ and SO₄²⁻ reduce the effective sulfate activity under high-thorium conditions, making excess sulfate necessary to achieve efficient BaSO₄ precipitation. Under optimized conditions, the radium co-precipitation recovery exceeded 80% at a Ba²⁺ concentration of 3 mM. Meanwhile, thorium exhibited negligible incorporation into the BaSO₄ phase and could be almost completely recovered via subsequent hydroxide precipitation. The proposed method features operational simplicity, use of common reagents, low cost, and compatibility with high-salinity matrices. It provides a feasible technical pathway for the subsequent production of high-purity ²²⁸Th or ²²⁴Ra and the preparation of ²²⁸Th/²¹²Pb or ²²⁴Ra/²¹²Pb generator systems. Full article

C. albicans small GTPase Ras1 belonging to the cAMP-Protein Kinase A (PKA) signaling pathway is a well-established master regulator of hyphal development, taking its environmental cues from N-acetylglucosamine (GlcNAc) as a carbon source. Iron is also known to induce filamentation in C. albicans. However, the influence of iron availability on Ras1-cAMP-PKA signaling in response to GlcNAc-induced filamentation has never been studied. In this study, we investigated the role of Ras1 in hyphal induction under varying iron conditions, using both in vitro systems and an in vivo model of mucosal colonization in Caenorhabditis elegans. Surprisingly, upon GlcNAc exposure, ∆/∆ras1 cells formed true hyphae exclusively under high-iron conditions, whereas its parent strain (CAI4-Ura+) showed hyphal formation irrespective of environmental iron levels. Further analysis revealed that this GlcNAc-mediated hyphal formation under high iron in ∆/∆ras1 cells was independent of cAMP levels but required the downstream effectors Efg1 and Tpk2. A similar iron-dependent pattern of hyphal formation in Δ/Δras1 cells was also observed in vivo in C. elegans. Transcriptomic analysis indicated that high iron induced robust expression of hypha-associated genes in ∆/∆ras1, accompanied by downregulation of BCY1, a negative regulator of PKA. Overexpression of BCY1 in ∆/∆ras1 cells completely blocked the iron-dependent hyphal formation, highlighting a previously unrecognized Ras1-independent, iron-responsive mechanism controlling PKA-mediated filamentation. Collectively, our findings reveal that increased environmental iron availability can bypass Ras1 to regulate hyphal development by limiting Bcy1 levels to allow PKA activation. This provides insights into how C. albicans can exploit iron replete host niches for enhanced pathogenicity, eliminating the need for key modulators such as Ras1. Full article

Accurate real-time soil moisture monitoring is critical for optimizing water use and ensuring crop health and food security. This study aims to calibrate and integrate low-cost capacitive soil moisture sensors into a solar-powered sensor node for real-time soil moisture monitoring in a loamy sand soil. Three capacitive soil moisture sensors were calibrated in the laboratory under controlled volumetric water content conditions (0–40%) using a constrained linear regression approach. The system was tested in a limited pilot-scale in a drip-irrigated onion field at the IWAD farm, Yagaba (North-East Region, Ghana). The results showed good agreement of the sensor readings with the soil moisture obtained using the gravimetric method (R² of 0.92–0.94, RMSE of 0.40–0.52%, and MAE of 0.35–0.39%) demonstrating the successful transfer of the calibration functions to field conditions. Soil moisture data was successfully monitored and transmitted from the nodes to a LoRa gateway via LoRaWAN (433 MHz) and from the gateway to a Raspberry Pi edge server via Wi-Fi. Data was stored both locally in SQLite on the Raspberry Pi and on the InfluxDB cloud. These results suggest that the developed system, when extensively validated under field conditions, can be used to support decision-making for data-driven IoT-based irrigation scheduling. Full article