Search Results (237)

Lung cancer remains a major cause of cancer-related death, highlighting the need for new molecular targets and novel therapeutics. Matrix metalloproteinases are key regulators of invasion and microenvironment remodeling, and among them, matrix metalloproteinase-12 (MMP12) is a particularly attractive candidate whose network-level effects in cancer are still poorly defined. Herein, we applied an integrative strategy that combines bioinformatics methods with experimental validation in non-small cell lung cancer (NSCLC) cells. Protein–protein interaction (PPI) and pathway analyses of MMP12-regulated genes identified 113 downstream targets enriched in the extracellular matrix, PI3K–AKT, and immune pathways, from which an eight-gene panel (MMP12, CD44, ADAM9, NFKBIA, PSME3, SPARCL1, CCL15, and APOA1) was prioritized as a biomarker signature. Guided by these predictions, we screened a 31-compound MMP12 inhibitor library and selected five leads (C1, C7, C9, C10, and C15) for testing in H1299 cells, with C9 showing the strongest antiproliferative activity. These compounds showed antimigratory activity (C1 achieving a 90% inhibition of wound closure at its IC₅₀ concentration), reduced clonogenic growth, cell cycle perturbation, and induction of apoptosis. Gene- and protein-expression analyses confirmed MMP12 suppression and modulation of the eight-gene panel. Upstream regulator predictions implicated reduced AKT signaling alongside an ADAM9-centered adaptive axis. Collectively, these findings highlight C1, C7, C9, C10, and C15 as promising MMP12 inhibitors, supporting their further development in preclinical lung cancer and nominating the eight-gene panel as a pharmacodynamic signature for MMP12-targeted therapies. Full article

Frequent extreme weather events exacerbate agricultural abiotic stress, with drought causing widespread yield loss. Tomato, a globally important vegetable sensitive to water deficit, has been predominantly studied under single-drought scenarios that poorly reflect recurrent field conditions. This study investigated physiological and molecular responses of two tomato genotypes to repeated drought stress. Results showed that the drought-sensitive genotype ‘TGTB’ exhibited faster ABA accumulation and more pronounced ABA-mediated stomatal closure. During the second drought cycle, stomatal pore length and width were significantly smaller than during the first drought, indicating a strong stress memory effect. In contrast, the drought-tolerant ‘LA1598’ showed minimal memory responses. Under extreme drought stress, primed and non-primed ‘TGTB’ plants showed significantly lower H₂O₂ content than controls, whereas primed ‘LA1598’ plants maintained a significantly lower O₂^·− production rate than non-primed plants during both extreme drought cycles. Antioxidant enzyme systems contributed to ROS homeostasis, supported by the regulation of key drought-responsive genes. This study demonstrates genotype-dependent memory capacity and reveals that drought priming enhances repeated drought tolerance through ABA-regulated stomatal adjustment. These findings provide a theoretical basis for improving tomato resilience to recurrent drought and supporting breeding of drought-tolerant varieties. Full article

Extremely premature newborns are predisposed to cardiovascular complications due to a number of factors, including myocardial immaturity, hemodynamic changes, and iatrogenic effects. There are few studies on myocardial strain in extremely premature infants during the early neonatal period. The objective of study was to assess the left ventricular (LV) segmental strain in extremely premature newborns during the early neonatal period by employing speckle-tracking echocardiography (STE). This prospective study examined 65 newborns with no signs of hemodynamic impairment during the first 72 h of life. The cohort had a range of birth weights (600–1500 g) and gestational ages (24–35 weeks). The peak strain in 18 LV segments during systole (peak S and time to peak S), and throughout the cardiac cycle (peak G and time to peak G), and during early systolic pre-stretch (peak P and time to peak P) were assessed in the longitudinal, circumferential, and radial directions. We obtained percentile tables of segmental strain characteristics in the longitudinal, circumferential, and radial directions. No dependence of segmental strain on the birth weight, gestational age, or arterial duct closure was found. A positive gradient of the longitudinal strain magnitude was observed from the base to the apex. The highest circumferential and radial strain were observed in LV septum. This study is the first to register and compare the longitudinal, circumferential, and radial LV strain using STE in extremely premature infants with no signs of hemodynamic disturbances during the first 72 h of life. Reference values for segmental strain were established. Full article

We assess precipitation and key atmospheric water-cycle terms over South America (SA) in three modern reanalyses—MERRA-2, ERA5, and CFSR/CFSv2—during 1980–2021. Two observation-based datasets (CPC Unified Gauge and MSWEP-V2) serve as references to bracket observational uncertainty. Diagnostics include regional means for the Tropical and Subtropical South Atlantic Convergence Zone (TSACZ, SSACZ) and southeastern South America (SESA), Taylor-diagram skill metrics, and a vertically integrated moisture-budget residual as a proxy for closure. All products reproduce the large-scale spatial and seasonal patterns, but disagreements persist over the Andes and parts of the central/northern Amazon. Relative to CPC/MSWEP-V2, MERRA-2 exhibits the smallest precipitation biases and the highest correlations, followed by ERA5; CFSR/CFSv2 shows a warm-season wet bias. Moisture-budget residuals are smallest in MERRA-2, moderate in ERA5, and largest in CFSR/CFSv2, with clear regional and seasonal dependence. These results document improvements in the new generation of reanalyses while highlighting persistent challenges in gauge-sparse and complex-orography regions. For hydroclimate applications that depend on internally consistent P, E, moisture-flux convergence, and runoff, MERRA-2 provides the most coherent depiction among the three, whereas ERA5 is a strong alternative when higher spatial/temporal resolution or dynamical fields are needed and CFSR/CFSv2 should be applied with caution for warm-season precipitation and closure-sensitive analyses. Full article

This study presents the first comprehensive investigation of direct supercritical water oxidation (SCWO) of microalgae biomass integrated with photobioreactor oxygen recovery for sustainable energy production. Laboratory-scale experiments were conducted on Nannochloropsis gaditana at optimized conditions (650 °C, 24 MPa, 1 min residence time), achieving extraordinary conversion efficiency of 99.99% at biomass concentrations as low as 0.5 wt%. Process simulation using Aspen Plus demonstrated that this integrated photobioreactor-SCWO system can recover oxygen produced during photosynthesis, reducing compressor energy demands by 10–15% compared to conventional air-fed systems. The coupled system achieved net thermal power outputs of 47–66 kW from a 1 kg/min microalgae feed at 5–10 wt% biomass concentration, corresponding to an overall system thermal efficiency of approximately 18%. CO₂ recovery via mono-ethanolamine absorption enabled 70–80% carbon cycle closure, while simultaneous nutrient recycling through the aqueous phase supports sustainable circular economy principles. This coupled photobioreactor-SCWO process represents an efficient pathway for energy recovery from wet microalgae biomass, eliminating the energy-intensive drying requirement (typically 60–70% of conventional processing energy) and achieving complete mineralization of organic compounds. The system demonstrates technical and energetic viability for scaling to pilot demonstration scale. Full article

As one of the most technically and managerially complex types of construction projects, super-high-rise buildings require deep multidisciplinary integration and intensive collaboration throughout their lifecycle. Conventional stage-based delivery models, such as the EPC, are often inadequate for handling this complexity. In recent years, the integrated Financing–Engineering, Procurement and Construction–Operation (F+EPC+O) model has emerged to address lifecycle governance challenges in building projects. This study explores how an investment-led F+EPC+O model builds dynamic capabilities to enable lifecycle collaboration in complex projects. It is based on a case study of the Xiamen Hemei Center and employs a qualitative case study approach to examine the operation of an internal F+EPC+O in the project. Drawing on multi-source data, including internal archives, BIM/CIM logs, and interviews, the findings identify three elements—lifecycle incentive alignment, internal power symmetry, and extended operation duration—that shape the Sensing–Seizing–Reconfiguring (SSR) capabilities of the approach. Specifically, Sensing is achieved through NPV-based decision frameworks and cross-stage trade-off lists; Seizing is achieved through BIM/CIM issue closure and joint rapid-cycle decision-making; and Reconfiguring is achieved through performance feedback and institutionalized knowledge repositories. The findings indicate that the SSR dynamic cycle transforms institutional integration into value co-creation, turning project complexity into a source of collaborative advantage. Full article

Despite technological advancements in mining, Chile lacks comprehensive risk management models for tailings storage facilities (TSFs), which hinders the prevention and mitigation of structural and environmental risks. This study aims to develop an integrated risk management model for TSFs in Chile, combining geological and mining engineering with an updated regulatory framework to enhance safety and reduce environmental impacts. The research adopts a mixed-methods approach. Qualitatively, it draws on 10 semi-structured interviews with engineers, geologists, academics, and professionals from the Chilean mining industry, selected through purposive sampling, to explore how and why the current risk management model should be improved. Quantitatively, it analyzes data from 303 surveys assessing the existing regulatory framework, a proposed new regulatory decree for Chile, and key variables to be considered in TSF risk management. The results present a new model that integrates geochemical and geotechnical characterization, process variables, in situ sensors, remote sensing, and artificial intelligence to generate dynamic risk indicators and early warning systems throughout the life cycle of the facility, including closure and liability valuation. Its multiscale design, adaptable to seismic and hydrogeological conditions and suitable for small- and medium-scale mining, overcomes existing static and fragmented approaches, enabling more effective decision-making with a focus on environmental and community safety. The study concludes that the model provides a robust and coherent tool for TSF risk management by integrating technical expertise, the current regulatory framework, and the management of key variables that enhance the ability to anticipate and mitigate structural and environmental risks. Full article

Background: Almaty, located in a mountain–valley basin, frequently experiences stagnant conditions that trap pollutants and cause sharp diurnal contrasts in air quality. Current forecasting systems either offer detailed physical realism at high computational cost or yield statistically accurate but physically inconsistent results. Urban air quality in mountain–valley cities is strongly shaped by thermal inversions and weak nocturnal ventilation that trap pollutants close to the surface. We present a hybrid physics–machine-learning framework that combines a Navier–Stokes surface-layer model with data-driven post-processing to produce short-term forecasts of wind, temperature, and particulate matter while preserving physical consistency. The approach captures diurnal ventilation patterns and the well-known negative linkage between near-surface wind and particulate loadings during wintertime inversions. Compared with purely statistical baselines, the hybrid system improves short-range forecast skill and maintains interpretability through physically grounded diagnostics. Beyond Almaty, the workflow is transferable to other mountain–valley environments and is directly actionable for early warning, traffic and heating-related emission management, and health-risk communication. By uniting physically meaningful fields with lightweight Machine Learning correction, the method offers a practical bridge between computational fluid dynamics and operational decision support for cities facing recurrent stagnation episodes. Aim: Develop and verify a method for the diagnostics and short-term forecasting of surface circulation and particle concentrations in Almaty (2024), ensuring physical consistency of fields, increased forecast accuracy on 6–24 h horizons, and interpretability of risk factors. Compared to purely statistical baselines (R² ≈ 0.55 for PM forecasts), our hybrid framework achieved a 16% gain in explained variance and reduced RMSE by 25%. This improvement was most evident during winter inversion episodes. Methods: This study introduces a hybrid modeling framework that integrates the Navier–Stokes equations with machine-learning algorithms to diagnose and forecast surface air circulation and particulate matter concentrations. The approach ensures both physical consistency and improved predictive accuracy for short-term horizons (6–24 h). The Navier–Stokes equations in the Boussinesq approximation, the energy equation, and K-closure particulate matter transport were used. The numerical solution is based on the projection method (convection—TVD/QUICK, pressure—Poisson equation). The ML module is gradient boosting and decision trees for meteorological parameters, lags, and diagnostic quantities. The 2024 data are cleaned, normalized, and visualized. Results: The hybrid model reproduces the diurnal cycle of ventilation and concentrations, especially during winter inversions. For 6 h: wind RMSE ≈ 1.2 m/s (R² ≈ 0.71), temperature RMSE ≈ 1.8 °C (R² ≈ 0.78), and particles RMSE ≈ 0.012 mg/m³ (R² ≈ 0.64). Errors are higher for 24 h. A negative relationship between wind and concentration was established: +1 m/s reduces the median by 10–15% during winter nights. Conclusions: The approach can be generalized to other mountain–valley cities beyond Almaty. Combining the physical model and ML correction improves short-term predictive ability and maintains physical consistency. The method is applicable for air quality risk assessment and decision support; further clarification of emissions and consideration of urban canyon geometry are required. The results support early-warning systems, health risk communication, and urban planning. Full article

A comprehensive numerical investigation of Fatigue Crack Growth (FCG) under negative stress ratios (R < 0) was conducted using the Finite Element Method (FEM) and the ANSYS Benchmark 19.2 SMART crack growth module on modified Compact Tension (CT) specimens. This study addresses the critical challenge posed by the compressive portion of cyclic loading, which traditional Linear Elastic Fracture Mechanics (LEFM) models often fail to capture accurately due to the complex interaction of crack closure and reversed plastic zones. The analysis focused on the evolution of the von Mises stress and maximum principal stress distributions at the crack tip across a range of stress ratios, including R = 0.1, −0.1, −0.2, −0.3, −0.4, −0.5, and −1.0. The results demonstrate a significant inverse correlation between fatigue life cycles and the magnitude of the negative stress ratio, consistent with the detrimental effect of increasing tensile stress. Crucially, the numerical simulation successfully captured the non-monotonic behavior of the crack tip stress field, revealing that the compressive load phase substantially alters the effective stress intensity factor range and the crack growth path, which was governed by the Maximum Tangential Stress (MTS) criterion. This research provides a validated computational methodology for accurately predicting FCG life in engineering components subjected to demanding, fully reversed, or compressive–dominant cyclic loading environments. Full article

This study investigates the fatigue behavior of pressurized pipelines under cyclic internal pressure, focusing on the influence of elastic and elastoplastic material responses on crack propagation. The Extended Finite Element Method (XFEM), implemented in Abaqus 2002, is used to model crack initiation and propagation without remeshing. The analysis first considers elastic behavior to estimate maximum stresses and stress intensity factors (SIFs) at crack tips, and then introduces an elastoplastic model to account for local plastic deformation in regions of high stress concentration, improving fatigue life prediction accuracy. The numerical approach is coupled with the Basquin and Manson–Coffin fatigue models and supported by a test matrix varying internal pressure amplitudes to systematically evaluate parameter interactions. The novelty of this work lies in the systematic study of the interaction between internal pressure, material nonlinearity, plastic zone evolution, crack closure, and fatigue life estimation. Unlike previous studies, the analysis includes detailed comparisons with analytical predictions and validated experimental data from the literature, ensuring the reliability of the model. The results show significant differences between the elastic and elastoplastic regimes: under 12 MPa, the maximum stress reached 352.5 MPa and fatigue life was 1639 cycles, while under 28 MPa, stress increased to 850 MPa and life dropped to a single cycle. These findings highlight the critical role of plastic deformation in fatigue crack growth and demonstrate that neglecting plasticity can greatly overestimate pipeline durability, providing a more realistic assessment of structural integrity in pressurized systems. Full article

This research presents a detailed Life Cycle Assessment (LCA) of 26 mm Crown cork metal closures used in glass bottle packaging, with the objective of quantifying and comparing their environmental impacts across all life cycle stages. This study adheres to ISO 14040 and ISO 14044 standards and utilizes Microsoft Excel for structuring and documenting input–output data across each phase. The LCA encompasses three primary stages: raw material production (covering iron ore extraction and steel manufacturing), manufacturing processes (including metal sheet printing, forming, and packaging of closures), and the transport phase (distribution to bottling facilities). During the Life Cycle Inventory (LCI), steel production emerged as the most environmentally burdensome phase. It accounted for the highest emissions of carbon dioxide (CO₂), carbon monoxide (CO), nitrogen oxides (NO_x), and sulphur oxides (SO_x), while emissions of heavy metals and volatile organic compounds were found to be negligible. The Life Cycle Impact Assessment (LCIA) was carried out using the Eco-Indicator 99 methodology, which organizes emissions into impact categories related to human health, ecosystem quality, and resource depletion. Final weighting revealed that steel production is the dominant contributor to overall environmental impact, followed by the manufacturing stage. In contrast, transportation exhibited the lowest relative impact. The interpretation phase confirmed these findings and emphasized steel production as the critical stage for environmental optimization. This study highlights the potential for substantial environmental improvements through the adoption of low-emission steel production technologies, particularly Electric Arc Furnace (EAF) processes that incorporate high percentages of recycled steel. Implementing such technologies could reduce CO₂ emissions by up to 68%, positioning steel production as a strategic focus for sustainability initiatives within the packaging sector. Full article

To investigate characteristic stress and energy evolution law of carbonaceous shale under dry–wet cycles and fissure angle, several samples with prefabricated fissure angles were prepared and subjected to the coupled influence of dry–wet cycles and loading. The results show that the closure stress, initiation stress, damage stress, and peak stress gradually increase with the increase in confining pressure, effectively suppressing the initiation and propagation of the crack. At the same time, the total energy, elastic energy, and dissipated energy at the crack characteristic stress are enhanced by a linear function relationship, significantly improving the bearing capacity and energy storage capacity of carbonaceous shale. The dry–wet cycle is regarded as the driving force of damage, reducing the crack characteristic stress and the total energy, elastic energy, and dissipated energy of crack characteristic stress. This results in a weakened capacity of the rock samples to store elastic strain energy, ultimately contributing to the damage degradation of carbonaceous shale. The anisotropic damage of rock is controlled by fissure angle. The crack characteristic stress and the total energy, elastic energy, and dissipated energy of crack characteristic stress with a 45° fissure angle is the smallest. Finally, the energy storage level at the damage stress (Kcd) can be used as an early warning indicator for rock failure. Full article

Background/Objectives: Endometrial cancer (EC), a malignancy arising from the uterine lining, is a leading gynecological cancer in developed countries. Syringic acid (SA), a naturally occurring phenolic compound, possesses various bioactivities including antioxidant, anti-inflammatory, chemoprotective, and anti-angiogenic properties. This study aimed to investigate the effects of SA on the proliferation and migration of RL95-2 EC cells, its protective role in normal endometrial stromal cells (HESCs), and the underlying molecular mechanisms. Furthermore, the potential synergistic anticancer effects of SA in combination with chemotherapeutic agents against EC were evaluated. Methods: Cell viability was assessed using nuclear fluorescence staining, the MTT assay, and clonogenic survival assay. Cell migration was evaluated through wound closure and Transwell migration assays. Gene expression levels were analyzed by the RT-PCR method. Results: SA significantly inhibited the proliferation of RL95-2 EC cells, with an IC₅₀ value of 27.22 μM. Co-treatment with SA and the chemotherapeutic agent doxorubicin (Dox) demonstrated an additive inhibitory effect. Mechanistically, both SA and the SA-Dox combination induced apoptosis by upregulating the expression of caspases-3, -8, and -9, increasing the expression of pro-apoptotic genes (Bax and Bad), and downregulating anti-apoptotic genes (Bcl-XL and Bcl-2). Cell cycle analysis revealed the downregulation of cyclin D and the upregulation of tumor suppressors p21 and p27, contributing to growth arrest. In addition, both SA and the combination treatment effectively suppressed cell migration by downregulating matrix metalloproteinases (MMPs) and β-catenin. SA treatment also induced the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and activated NF-κB signaling, leading to an elevated expression of inflammatory mediators such as COX-2 and iNOS. Furthermore, SA promoted oxidative stress in RL95-2 cells by inhibiting the Nrf2 pathway and reducing the expression and activities of antioxidant enzymes including catalase, glutathione peroxidase, and superoxide dismutase, thereby enhancing reactive oxygen species (ROS) accumulation. In contrast, in lipopolysaccharide-stimulated HESC cells, SA attenuated inflammation and ROS generation, indicating its selective cytoprotective role in normal endometrial cells. Conclusions: SA may serve as a promising adjuvant candidate to enhance chemotherapeutic efficacy while protecting normal cells by mitigating inflammation and oxidative stress. Full article

The increase in municipal solid waste (MSW) generation and its inefficient management have caused significant environmental impacts, particularly in developing countries such as Mexico. In the central region, final disposal in uncontrolled sites (UCSs) remains a common practice despite its negative effects on the environment and public health. These impacts have been underestimated due to the scarcity of studies and the lack of technological alternatives aimed at mitigating them. In response to this problem, Life Cycle Assessment (LCA) emerges as a strategic tool to quantify these effects and to guide decision-making toward more sustainable management. The objective of this study was to evaluate the environmental impacts of a UCS using LCA, considering four scenarios: a baseline (E0) representing the current system conditions and three alternative scenarios (E1, E2, and E3) designed to explore potential improvements in environmental performance and to identify a feasible option under the socioeconomic conditions of a municipality in central Mexico. The functional unit was defined as the treatment of one tonne of MSW. The system boundaries included the separation of recyclable inorganic waste (RIW), the treatment of organic waste (OW) through composting and anaerobic digestion (AD), and the final disposal of mixed waste (MW) in UCSs and sanitary landfills. The assessment was performed using SimaPro Analyst v9.6 software and the ReCiPe methodology. The E0 scenario exhibited the highest environmental burdens, whereas E2 and E3 reduced the disposal of MW from 85.92% to 52.57% and emissions by 78.9%. E3 showed the lowest overall impact by integrating mechanical separation, AD, and controlled landfill disposal. E2, which employed composting instead of AD, proved to be a viable alternative for resource-constrained contexts. The results support the closure of uncontrolled sites and encourage the transition toward integrated systems that incorporate valorization technologies, which are urgently needed to achieve the Sustainable Development Goals. Full article

The growing implementation of close-to-nature forestry practices in the management of northern forests, characterized by dispersed harvesting operations, has heightened the importance of minimizing damage to residual stands as a key aspect of sustainable forest management. The objective of this study is to examine and compare the resistance of various tree species and diameter classes to wounds incurred during logging operations of differing sizes, intensities, and locations. In addition, the research aims to assess temporal changes in wound characteristics, including healing and closure processes, across species. This long-term, 18-year investigation was conducted in the Kheyrud Forest, located within the Hyrcanian broadleaf forest region of northern Iran, to evaluate the dynamics of wound healing in residual trees following ground-based skidding operations. Through a comprehensive assessment of 272 wounded trees across six species, we demonstrate that species significantly influences healing ratio (Kruskal–Wallis, p < 0.01), with Oriental beech (Fagus orientalis Lipsky) (50.6%) showing superior recovery compared to the Chestnut-leaved oak (Quercus castaneifolia) (37.5%). Healing ratio decreased with larger diameter at breast height (DBH) (R² = 0.114, p < 0.01), while absolute healed area increased. Larger areas (>1000 cm²) reduced healing by 42.3% versus small wounds (<500 cm²) (R² = 0.417, p < 0.01). Severe wounds (deep gouges) showed 19% less healing than superficial injuries (p = 0.003). Circular wounds healed significantly better than rectangular forms (χ² = 24.92, p < 0.001). Healing ratio accelerated after the first decade, reaching 69% by year 17 (R² = 0.469, p < 0.01). Wound height (p = 0.117) and traffic intensity (p = 0.65) showed no statistical impact. Contrary to expectations, stem position had no significant effect on wound recovery, whereas wound geometry proved to be a critical determinant. The findings highlight that appropriate species selection, minimizing wound size (to less than 500 cm²), and adopting extended cutting cycles (exceeding 15 years) are essential for enhancing residual stand recovery in close-to-nature forestry systems. Full article