Search Results (1,361)

Spilled hydrocarbons released from oil pipeline accidents can result in long-term environmental contamination and significant damage to habitats. In this regard, evaluating actions in response to vulnerability scenarios is fundamental to emergency management and groundwater integrity. To this end, understanding the trajectories and their influence on the various parameters and characteristics of the contaminant’s fate through accurate numerical simulations can aid in developing a rapid remediation strategy. This paper develops a numerical model using the CactusHydro code, which is based on a high-resolution shock-capturing (HRSC) conservative method that accurately follows sharp discontinuities and temporal dynamics for a three-phase fluid flow. We analyze nine different emergency scenarios that represent the breaking of a diesel oil onshore pipeline in a porous medium. These scenarios encompass conditions such as dry season rupture, rainfall-induced saturation, and varying pipeline failure pressures. The influence of the spilled oil pressure and water saturation in the unsaturated zone is analyzed by following the saturation contour profiles of the three-phase fluid flow. We follow with the high-accuracy formation of shock fronts of the advective part of the migration. Additionally, the mass distribution of the expelled contaminant along the porous medium during the emergency is analyzed and quantified for the various scenarios. The results obtained indicate that the aquifer contamination strongly depends on the pressure outflow in the vertical flow. For a fixed pressure value, as water saturation increases, the mass of contaminant decreases, while the contamination speed increases, allowing the contaminant to reach extended areas. This study suggests that, even for LNAPLs, the distribution of leaked oil depends strongly on the spill pressure. If the pressure reaches 20 atm at the time of pipeline failure, then contamination may extend as deep as two meters below the water table. Additionally, different seasonal conditions can influence the spread of contaminants. This insight could directly inform guidelines and remediation measures for spill accidents. The CactusHydro code is a valuable tool for such applications. Full article

Background and Aims: Triple-negative breast cancer (TNBC) is a clinically aggressive malignancy marked by rapid disease progression, limited therapeutic avenues, and high recurrence risk. Ferroptosis an iron-dependent, lipid peroxidation-driven form of regulated cell death that has emerged as a promising therapeutic vulnerability in oncology. This study delineates the ferroptosis-associated molecular architecture of TNBC to identify key regulatory genes with prognostic and translational significance. Methods: Transcriptomic profiles from the GSE103091 dataset (130 TNBC and 30 normal breast tissue samples) were analyzed to identify ferroptosis-related differentially expressed genes (DEGs) using GEO2R. Protein–protein interaction (PPI) networks were constructed via STRING and GeneMANIA, with functional enrichment performed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses. Prognostic relevance was evaluated using GEPIA, BC-GenExMiner, and Kaplan–Meier Plotter survival analyses. Results: Six ferroptosis drivers (MAPK1, TLR4, IFNG, ATM, ULK2, and ATF3) and five suppressors (NFS1, GCLC, TP63, CD44, and SRC) were identified alongside HMOX1, a bifunctional regulator with context-dependent pro- and anti-ferroptotic activity. Enrichment analyses revealed significant associations with oxidative stress regulation, autophagy, immune modulation, and tumor progression pathways. Elevated IFNG expression was consistently linked to improve overall, disease-free, and distant metastasis-free survival, underscoring its dual function in antitumor immunity and ferroptosis sensitization. Conclusions: Ferroptosis represents a critical axis in TNBC pathophysiology, with IFNG emerging as both a prognostic biomarker and a viable therapeutic target. These insights provide a mechanistic foundation for integrating ferroptosis-inducing agents with immunotherapeutic modalities to enhance clinical outcomes and overcome therapeutic resistance in TNBC. Full article

To ensure the mechanical performance of gas turbine hollow blades under high-temperature conditions, the application of aluminide high-temperature protective coatings on the inner gas flow channel surfaces of hollow blades via chemical vapor deposition (CVD) has become a critical measure for enhancing blade safety. This study employs computational fluid dynamics (CFD) to investigate the flow field within CVD reactors and the influences of deposition processes on the chemical reaction rates at sample surfaces, thereby guiding the optimization of CVD reactor design and deposition parameters. Three distinct CVD reactor configurations are examined to analyze the flow characteristics of precursor gases and the internal flow field distributions. The results demonstrate that Model A, featuring a bottom-positioned outlet and an extended inlet, exhibits a larger stable deposition zone with more uniform flow velocities near the sample surface, thereby indicating the formation of higher-quality aluminide coatings. Based on Model A, CFD simulations are conducted to evaluate the effects of process parameters, including inflow velocity, pressure, and temperature, on aluminide coating deposition. The results show that the surface chemical reaction rate increases with inflow velocity (0.0065–6.5 m/s), but the relative change rate (ratio of reaction rate to flow rate) shows a declining trend. Temperature variations (653–1453 K) induce a trapezoidal-shaped trend in deposition rates: an initial increase (653–1053 K), followed by stabilization (1053–1303 K), and a subsequent decline (>1303 K). The underlying mechanisms for this trend are discussed. Pressure variations (0.5–2 atm) reveal that both excessively low and high pressures reduce surface reaction rates, with optimal performance observed near 1 atm. This study provides a methodology and insights for optimizing CVD reactor designs and process parameters to enhance aluminide coating quality on turbine blades. Full article

The hyperbaric environment, to which many categories of workers are exposed, can provoke injuries that can lead to various types of disorders. A major part of the studies aiming to explore the causes/effects leading to these injuries are conducted in vivo. In the present manuscript, we describe the effects on osteoblast cell cultures stressed in a hyperbaric purpose-built chamber, using an in vitro model to analyze the affected pathways. A hyperbaric chamber for cell cultures was constructed by adapting a pressurized test chamber originally designed for technical use. The MG-63 cell line and human primary osteoblasts were placed into this chamber at different atm and exposure times, at 37 °C. After treatment, the chamber was depressurized by performing controlled decompression stops. Then, the pro-inflammatory cytokines and bone tissue biomarker expression were analyzed. The stress conditions induced the overexpression of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α, along with reactive oxygen species release. Moreover, the alteration of bone tissue marker production was observed. In particular, the increase in Receptor Activator of NF-κB Ligand (RANKL) and the decrease in Osteoprotegerin (OPG) were detected. Further modulation was observed regarding other biomarkers, Alkaline phosphatase, Osteocalcin, Bone Morphogenetic Protein-2, and mainly Collagen type I, all of which were downregulated by treatment. Taken together, these findings account for certain illnesses, such as dysbaric osteonecrosis, diagnosed in workers exposed to a hyperbaric environment. Inflammation induced by this kind of stress affects several factors involved in bone tissue homeostasis, leading to bone injuries, which are among the typical disorders observed in divers. Full article

The toxicity of lead in conventional perovskites and their inherent chemical instability impede the commercialization of perovskite-based optoelectronics. Therefore, it is vital to develop chemically stable and environmentally friendly Pb-free alternatives. Recently, zero-dimensional (0D) all-inorganic Cs₂ZnCl₄ doped with Sn(II) has emerged as a promising candidate, exhibiting superior chemical robustness, minimal biotoxicity, and exceptional optoelectronic properties. In this work, pressure effects on structure and optical properties in Sn(II)-doped all-inorganic zero-dimensional halide perovskite are investigated both experimentally and theoretically. The structure–property relationship of Sn(II)-doped Cs₂ZnCl₄ is studied using high-pressure techniques. Piezochromism, accompanied by a remarkable change in emission color from orange/red and green to orange/yellow, was obtained from 1 atm to 22.5 GPa. Angle dispersive synchrotron X-ray diffraction (ADXRD) patterns and Raman spectra manifest that the material underwent an isostructural phase transition followed by amorphization with increasing pressure. The piezochromism and band gap engineering originate from the pressure-induced lattice compression and isostructural phase transition. This work advances STE emission studies and provides a robust strategy to boost emission efficiency and to construct multifunctional materials with piezochromism in environmentally friendly perovskites, thus facilitating diverse future applications. Full article

Gastric cancer remains a significant global health challenge, with regional and demographic disparities in incidence, mortality, and treatment outcomes. Despite advances in screening and early detection, prognosis remains poor for many patients, particularly those with advanced disease. Recent insights into DNA damage response pathways have uncovered critical molecular vulnerabilities in gastric tumors, including frequent TP53 mutations, ARID1A loss, ATM deficiency, and oncogene-driven replication stress, which render these cancers highly dependent on the ATR–CHK1 axis for survival. This review synthesizes current clinical and preclinical evidence on ATR and CHK1 inhibitors as therapeutic strategies in gastric cancer. Emphasis is placed on synthetic lethality, immune modulation, and the potential for combination regimens with chemotherapy, radiotherapy, or immune checkpoint blockade. Mechanisms of resistance, including transcription-associated replication stress modulation and bypass signaling networks, are discussed, alongside strategies to predict and overcome therapeutic failure. The review also highlights the importance of biomarker-guided patient selection, adaptive dosing to reduce toxicity, and refined pharmacodynamic monitoring to enhance therapeutic precision. Collectively, these insights support the rational integration of ATR–CHK1 inhibitors into clinical protocols for biomarker-defined gastric cancer subsets and underscore their promise Full article

During a thermal runaway, Lithium-ion battery cells are subjected to a large increase in temperature, which will vaporize and potentially thermally degrade their liquid electrolyte. The formation of gas in the battery cell will increase the pressure until the flammable gases vent and potentially lead to a fire incident. While the pyrolysis chemistry of the electrolyte components has been studied near atmospheric pressure, the effect of pressure has not been investigated. This study was undertaken to better understand the effect of pressure on the thermal dissociation of two common linear electrolyte components, diethyl carbonate (DEC) and ethyl methyl carbonate (EMC). The pyrolysis of DEC and EMC was studied in the gas phase, in 99.75% He/Ar, and was carried out at high temperatures and for pressures near 5.5 atm. The time-resolved CO formation was measured using a quantum cascade laser, providing a unique experimental dataset. A detailed chemical kinetics analysis was performed to understand the effect of pressure on DEC and EMC, with CO time-history results obtained in similar conditions at near-atmospheric pressure for DEC and EMC serving as baselines for comparison. Numerical predictions using detailed chemical kinetics mechanisms from the literature were carried out, and reaction pathways at different pressures were highlighted to emphasize the effect of pressure on the pyrolysis chemistry. Full article

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, highlighting the urgent need for novel therapeutic strategies. This study aimed to investigate the anticancer potential of sodium pentaborate pentahydrate (NaB) in CRC by evaluating its effects on human colorectal cancer cell lines and elucidating underlying molecular mechanisms. Methods: The cytotoxic and molecular effects of NaB were assessed in three human CRC cell lines (HCT-116, HT-29, and COLO-205) and one normal colon epithelial cell line (CCD-18CO). Cell viability assays were conducted to determine time- and dose-dependent responses. Apoptosis, cell cycle progression, colony formation, and migration capacity were evaluated. Gene and protein expression analyses were performed to examine apoptosis-related, DNA damage response, cell cycle, and Hippo signaling pathway components. Results: NaB significantly reduced cancer cell viability in a time- and dose-dependent manner, with minimal cytotoxicity to normal colon cells. It induced marked apoptosis, especially in HCT-116 and COLO-205 cells, and caused G2/M cell cycle arrest. In HCT-116 cells, NaB suppressed proliferation by downregulating PCNA and MKI-67 and reduced colony formation and migration. Molecular analyses revealed upregulation of pro-apoptotic BAX and downregulation of BCL-2, ATM, ATR, and cell cycle–related genes. NaB also inhibited oncogenic Hippo signaling by enhancing YAP1 phosphorylation and decreasing CTGF and CYR61 expression. Conclusions: These findings demonstrate that sodium pentaborate pentahydrate exerts selective anticancer effects on colorectal cancer cells through the induction of apoptosis, cell cycle arrest, and suppression of key oncogenic pathways. NaB represents a promising candidate for further development as a therapeutic agent in CRC treatment. Full article

As a new type of production factor, data possesses multidimensional application value, and its pivotal role is becoming increasingly prominent in the aviation sector. Data sharing can significantly enhance the utilization efficiency of data resources and serves as one of the key tasks in building smart civil aviation. However, currently, data silos are pervasive, with vast amounts of data only being utilized and analyzed within limited scopes, leaving their full potential untapped. The challenges in data sharing primarily stem from three aspects: (1) Data owners harbor concerns regarding data security and privacy. (2) The highly dynamic and real-time nature of aviation operations imposes stringent requirements on the timeliness, stability, and reliability of data sharing, thereby constraining its scope and extent. (3) The lack of reasonable incentive mechanisms results in insufficient motivation for data owners to share. Consequently, addressing the issue of aviation big data sharing holds significant importance. Since the release of the Bitcoin whitepaper in 2008, blockchain technology has achieved continuous breakthroughs in the fields of data security and collaborative computing. Its unique characteristics—decentralization, tamper-proofing, traceability, and scalability—lay the foundation for its integration with aviation. Blockchain can deeply integrate with air traffic management (ATM) operations, effectively resolving trust, efficiency, and collaboration challenges in distributed scenarios for ATM data. To address the heterogeneous data usage requirements of different ATM stakeholders, this paper constructs a blockchain-based multi-level data security sharing architecture, enabling fine-grained management and secure collaboration. Furthermore, to meet the stringent timeliness demands of aviation operations and the storage pressure posed by massive data, this paper optimizes blockchain storage deployment and consensus mechanisms, thereby enhancing system scalability and processing efficiency. Additionally, a dual-mode data-sharing solution combining raw data sharing and model sharing is proposed, offering a novel approach to aviation big data sharing. Security and formal analyses demonstrate that the proposed solution is both secure and effective. Full article

This study presents an approach based on machine learning (ML) techniques to analyze the relationship between emergency room (ER) admissions for cardiorespiratory diseases (CRDs) and environmental factors. The aim of this study is the development and verification of an interpretable machine learning framework applied to environmental and health data to assess the relationship between environmental factors and daily emergency room admissions for cardiorespiratory diseases. The model’s predictive accuracy was evaluated by comparing simulated values with observed historical data, thereby identifying the most influential environmental variables and critical exposure thresholds. This approach supports public health surveillance and healthcare resource management optimization. The health and environmental data, collected through meteorological sensors and air quality monitoring stations, cover eleven years (2013–2023), including meteorological conditions and atmospheric pollutants. Four ML models were compared, with XGBoost showing the best predictive performance (R² = 0.901; MAE = 0.047). A 10-fold cross-validation was applied to improve reliability. Global model interpretability was assessed using SHAP, which highlighted that high levels of carbon monoxide and relative humidity, low atmospheric pressure, and mild temperatures are associated with an increase in CRD cases. The local analysis was further refined using LIME, whose application—followed by experimental verification—allowed for the identification of the critical thresholds beyond which a significant increase in the risk of hospital admission (above the 95th percentile) was observed: CO > 0.84 mg/m³, P_atm ≤ 1006.81 hPa, Tavg ≤ 17.19 °C, and RH > 70.33%. The findings emphasize the potential of interpretable ML models as tools for both epidemiological analysis and prevention support, offering a valuable framework for integrating environmental surveillance with healthcare planning. Full article

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Adipose tissue inflammation contributes to obesity-induced insulin resistance. However, increasing evidence shows that high BMI (obesity) is not an accurate predictor of poor metabolic health in individuals. The molecular mechanisms regulating the metabolically activated M1 macrophage phenotype in the adipose tissues leading to insulin resistance remain largely unknown. Although the Janus Kinase (Jak)/signal transducer and activator of transcription 3 (Stat3) signaling in myeloid cells are known to promote the M2 phenotype in tumors, we demonstrate here that the Jak2/Stat3 pathway amplifies M1-mediated adipose tissue inflammation and insulin resistance under metabolic challenges. Ablating Jak2 in the myeloid compartment reduces insulin resistance in obese mice, which is associated with a decrease in infiltration of adipose tissue macrophages (ATMs). We show that the adoptive transfer of Jak2-deficient myeloid cells improves insulin sensitivity in obese mice. Furthermore, the protection of obese mice with myeloid-specific Stat3 deficiency against insulin resistance is also associated with reduced tissue infiltration by macrophages. Jak2/Stat3 in the macrophage is required for the production of pro-inflammatory cytokines that promote M1 macrophage polarization in the adipose tissues of obese mice. Moreover, free fatty acids (FFAs) activate Stat3 in macrophages, leading to the induction of M1 cytokines. Silencing the myeloid cell Stat3 with an in vivo siRNA targeted delivery approach reduces metabolically activated pro-inflammatory ATMs, thereby alleviating obesity-induced insulin resistance. These results demonstrate Jak2/Stat3 in myeloid cells is required for obesity-induced insulin resistance and inflammation. Moreover, targeting Stat3 in myeloid cells may be a novel approach to ameliorate obesity-induced insulin resistance. Full article

Rouaite (Cu₂(OH)₃NO₃) long hexagonal multilayered nanoplates with high purity and high crystallinity were prepared from acidic reaction solution (pH = 4.4–4.8) with the assistance of ZnO. The ZnO-assisted strategy is remarkably different from the conventional synthetic protocol that was regularly carried out in alkaline solution (pH > 11). The rouaite multilayer nanoplates displayed exceptionally high catalytic activity in the catalytic wet peroxide oxidation (CWPO) of Congo red (CR). The catalytic efficiency for CR decolorization achieved an impressive 96.3% in 50 min under near-neutral (pH = 6.76) and ambient conditions (T = 20 °C, p = 1 atm), without increasing the temperature and/or decreasing the pH value to acidic region (pH = 2–3) as is commonly employed in CWPO process for improved degradation efficiency. Full article

The ataxia–telangiectasia-mutated (ATM) protein plays a crucial role in the DNA damage response, particularly in the homologous recombination (HR) pathway. This study aimed to assess the impact of deleterious ATM variants on homologous recombination deficiency (HRD) and response to PARP inhibitors (PARPi) in melanoma patients, using a cell line established from melanoma tissue of a patient carrying the c.5979_5983del germline ATM variant. Despite proven loss of heterozygosity, lack of ATM activation, and HRD, our model did not show sensitivity to PARPi. We assessed the potential contribution of the Schlafen family member 11 (SLFN11) helicase, whose expression is inversely correlated with PARPi sensitivity in other cancers, to the observed resistance. The ATM mutant cell line lacked SLFN11 expression and featured hypermethylation-mediated silencing of the SLFN11 promoter. While sensitive to the ATR inhibitor (ATRi), the addition of ATRi to PARPi was unable to overcome the resistance. Our findings suggest that ATM mutational status and HRD alone do not adequately account for variations in sensitivity to PARPi in our model. A comprehensive approach is essential for optimizing the exploitation of DNA repair defects and ultimately improving clinical outcomes for melanoma patients. Full article

Cells are assaulted daily by stresses that jeopardize genome integrity. Primary human cells adapt their response to the intensity of replication stress (RS) in a diphasic manner: below a stress threshold, the canonical DNA damage response (cDDR) is not activated, but a noncanonical cellular response, low-level stress-DDR (LoL-DDR), has recently been described. LoL-DDR prevents the accumulation of premutagenic oxidized bases (8-oxoguanine) through the production of ROS in an adaptive way. The production of RS-induced ROS (RIR) is tightly controlled: RIR are excluded from the nucleus and are produced by the NADPH oxidases DUOX1/DUOX2, which are controlled by NF-κB and PARP1; then, RIR activate the FOXO1-detoxifying pathway. Increasing the intensity of RS suppresses RIR via p53 and ATM. Notably, LoL-DDR is dysregulated in cancer cell lines, in which RIR are not produced by NADPH oxidases, are not detoxified under high-level stress, and favor the accumulation of 8-oxoguanine. LoL-DDR dysregulation occurred at an early stage of cancer progression in an in vitro model. Since, conversely, ROS trigger RS, this establishes a vicious cycle that continuously jeopardizes genome integrity, fueling tumorigenesis. These data reveal a novel type of ROS-controlled DNA damage response and demonstrate the fine-tuning of the cellular response to stress. The effects on genomic stability and carcinogenesis are discussed here. Full article