Search Results (104,185)

FMS-like tyrosine kinase 3 (FLT3) is a crucial regulator of normal hematopoiesis, with high expression in hematopoietic stem and progenitor cells. Beyond its role in stem cell survival and proliferation, FLT3 signaling is essential for immune regulation, particularly dendritic cell differentiation and NK cell expansion. In acute myeloid leukemia (AML), FLT3 mutations—most commonly internal tandem duplications (FLT3-ITD) and tyrosine kinase domain (FLT3-TKD) substitutions—are among the most frequent genetic alterations, driving constitutive activation of proliferative and antiapoptotic pathways and conferring adverse prognosis. The clinical development of FLT3 inhibitors has been a decades-long endeavor. Early multikinase agents established proof-of-concept but were hampered by off-target effects and incomplete efficacy. The subsequent generation of potent and selective inhibitors has transformed outcomes, culminating in FDA approvals of midostaurin, quizartinib, and gilteritinib. Together with allogeneic transplantation, these agents have reshaped the treatment paradigm for FLT3-mutant AML, converting a historically high-risk subset into one with realistic prospects for long-term survival. Despite these advances, challenges remain. Resistance emerges through cell-intrinsic mechanisms such as acquisition of secondary TKD or RAS pathway mutations, metabolic reprogramming, and antiapoptotic shifts, as well as cell-extrinsic mechanisms mediated by the bone marrow microenvironment, including cytokine support, stromal CYP3A4 metabolism, and retinoid inactivation. These pathways sustain measurable residual disease (MRD), the key predictor of relapse. Rational combination strategies and MRD-directed approaches are therefore essential to fully realize the curative potential of FLT3 inhibition. Full article

This study explores the photoprotective and antioxidant potential of cosmetic emulsions formulated with Alnus glutinosa (black alder) extracts. Extraction of bioactive compounds was performed using Soxhlet, ultrasound-assisted, and microwave-assisted techniques with ethanol and water as solvents. The phytochemical profiles of the resulting extracts were characterized via UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), and liquid chromatography–high-resolution mass spectrometry (LC-HRMS). The extracts were incorporated into oil-in-water emulsions and assessed for antioxidant activity using the DPPH radical scavenging assay, pH and viscosity stability, and color L*a*b* values. Among the extraction methods, ethanol-based Soxhlet extraction yielded the highest concentration of bioactive compounds and demonstrated superior antioxidant and photoprotective efficacy. This is the first report that evaluates the antioxidant properties of A. glutinosa-enriched emulsions, supporting their application as multifunctional, plant-derived cosmeceuticals for skin protection. Full article

Background: Slow-transit constipation (STC) lacks durable and safe prokinetics. Deglycosylated-azithromycin (Deg-AZM), a novel small-molecule transgelin agonist that restores colonic motility in STC, has been approved for clinical trials in 2024. Objectives: This study aimed to assess the genetic toxicity and embryo–fetal development (EFD) toxicity of Deg-AZM through a series of standardized non-clinical safety studies. Methods: We conducted Ames, in vivo micronucleus, and chromosomal aberration tests to evaluate genotoxicity. Acute and 28-day repeated-dose oral toxicity studies were performed in Sprague-Dawley rats. EFD toxicity was assessed in pregnant rats administered Deg-AZM from gestation day (GD) 6 to 15. Toxicokinetic analyses were integrated into repeated-dose and EFD studies. Results: Deg-AZM demonstrated no mutagenic potential in the bacterial reverse-mutation assay at concentrations up to 2500 µg/plate (with metabolic activation) or 150 µg/plate (without metabolic activation). No clastogenic effects were observed in micronucleus or chromosomal aberration assays. The median lethal dose (LD₅₀) exceeded 1600 mg/kg in acute oral toxicity. In the 28-day study, no adverse effects were observed at doses up to 600 mg/kg, though mild hematological and hepatic changes were noted at high doses, all of which were reversible. In the EFD study, Deg-AZM did not induce maternal toxicity, teratogenicity, or adverse fetal outcomes at doses up to 600 mg/kg. Conclusions: Deg-AZM demonstrates a favorable safety profile with no evidence of genetic toxicity or developmental harm at pharmacologically relevant doses, supporting its further development as a therapeutic agent for STC. Full article

Accurate prediction of the ultimate bearing capacity (UBC) of single piles is essential for safe and economical foundation design, as it directly impacts construction safety and resource efficiency. This study aims to develop a hybrid prediction framework integrating Genetic Algorithm (GA) and Particle Swarm Optimization (PSO) to optimize a Backpropagation Neural Network (BPNN). GA performs global exploration to generate diverse initial solutions, while PSO accelerates convergence through adaptive parameter updates, balancing exploration and exploitation. The primary objective of this study is to enhance the accuracy and reliability of UBC prediction, which is crucial for informed decision-making in geotechnical engineering. A dataset consisting of 282 high-strain dynamic load tests was employed to assess the performance of the proposed GA-PSO-BPNN model in comparison with CNN, XGBoost, and traditional dynamic formulas (Hiley, Danish, and Winkler). The GA-PSO-BPNN achieved an R² of 0.951 and an RMSE of 660.13, outperforming other AI models and traditional approaches. Furthermore, SHAP (SHapley Additive exPlanations) analysis was conducted to evaluate the relative importance of input variables, where SHAP values were used to explain the contribution of each feature to the model’s predictions. The findings indicate that the GA-PSO-BPNN model provides a robust, cost-efficient, and interpretable approach for UBC prediction, which aligns with current sustainability goals by optimizing resource usage in foundation design. This model shows significant potential for practical use across various geotechnical settings, contributing to safer, more sustainable infrastructure projects. Full article

Corn (Zea mays L.) ranks among the most important cereal crops globally, extensively cultivated for food, animal feed, and industrial applications. Its large-scale production generates substantial amounts of agricultural residues such as cobs, husks, stalks, leaves and other, which are often underutilized, leading to environmental concerns. Due to their high carbon content, lignocellulosic structure, and abundant availability, these residues represent a sustainable and low-cost raw material for the synthesis of activated carbon. Corn waste-derived activated carbon has emerged as a promising material for the efficient removal of heavy metals from aqueous solutions. Its high surface area, well-developed porosity, and adjustable surface chemistry, referring to the functional groups on the adsorbent surface that can be modified to enhance affinity toward metal ions, facilitate effective adsorption. This review provides a comprehensive overview of (1) the potential of corn waste biomass as a precursor for activated carbon production, (2) methods of carbonization and activation that influence the textural and chemical properties of the resulting adsorbents, (3) adsorption performance for heavy metal removal under varying experimental parameters such as pH, initial concentration, contact time, and adsorbent dosage, (4) adsorption mechanisms responsible for heavy metal uptake. Reported maximum adsorption capacities vary for different metals, ranging from 2.814–206 mg/g for lead, 0.21–87.72 mg/g for cadmium, 9.6246–175.44 mg/g for chromium, and 0.724–643.92 mg/g for copper. Utilizing corn waste not only provides an eco-friendly approach for managing agricultural residues but also supports the development of efficient adsorbents. Nevertheless, challenges such as scaling up production and evaluating adsorbent performance in real wastewater samples remain and require further investigation. Finally, the review highlights key challenges and knowledge gaps in current research and offers recommendations for future studies aimed at advancing the practical application of corn waste–based activated carbons in water treatment. Full article

Coagulation–flocculation, historically reliant on simple inorganic salts, has evolved into a technically sophisticated process that is central to the removal of turbidity, suspended solids, organic matter, and an expanding array of micropollutants from complex wastewaters. This review synthesizes six decades of research, charting the transition from classical aluminum and iron salts to high-performance polymeric, biosourced, and hybrid coagulants, and examines their comparative efficiency across multiple performance indicators—turbidity removal (>95%), COD/BOD reduction (up to 90%), and heavy metal abatement (>90%). Emphasis is placed on recent innovations, including magnetic composites, bio–mineral hybrids, and functionalized nanostructures, which integrate multiple mechanisms—charge neutralization, sweep flocculation, polymer bridging, and targeted adsorption—within a single formulation. Beyond performance, the review highlights persistent scientific gaps: incomplete understanding of molecular-scale interactions between coagulants and emerging contaminants such as microplastics, per- and polyfluoroalkyl substances (PFAS), and engineered nanoparticles; limited real-time analysis of flocculation kinetics and floc structural evolution; and the absence of predictive, mechanistically grounded models linking influent chemistry, coagulant properties, and operational parameters. Addressing these knowledge gaps is essential for transitioning from empirical dosing strategies to fully optimized, data-driven control. The integration of advanced coagulation into modular treatment trains, coupled with IoT-enabled sensors, zeta potential monitoring, and AI-based control algorithms, offers the potential to create “Coagulation 4.0” systems—adaptive, efficient, and embedded within circular economy frameworks. In this paradigm, treatment objectives extend beyond regulatory compliance to include resource recovery from coagulation sludge (nutrients, rare metals, construction materials) and substantial reductions in chemical and energy footprints. By uniting advances in material science, process engineering, and real-time control, coagulation–flocculation can retain its central role in water treatment while redefining its contribution to sustainability. In the systems envisioned here, every floc becomes both a vehicle for contaminant removal and a functional carrier in the broader water–energy–resource nexus. Full article

Planetary gear trains offer numerous advantages over traditional gear systems, including high efficiency, the ability to handle large torque loads, and significant reductions in mass and size for the same torque capacity. However, their relatively complex design necessitates the use of optimization techniques to identify the most suitable configurations for specific applications. A key requirement for effective optimization is a mathematical model that accurately captures the essential operational characteristics of the system. Moreover, the optimization process must account for multiple, often conflicting, objectives. This paper focuses on the multicriteria optimization of a three-stage planetary gear train intended for use in a road vehicle winch. The development of the optimization model involves defining the objective functions, decision variables, and constraints. Optimization criteria were based on the following characteristics: overall volume, mass, transmission efficiency, and the production costs of the gear pairs. In addition to identifying the group of solutions that are Pareto optimal, the model employs the weighted coefficient method to select a single optimal solution from this set. The selected solution is then analyzed through simulation to assess potential gear failure scenarios. By combining optimization techniques with simulation and contact analysis, this study contributes to improving the reliability of planetary gear transmissions. Full article

Background/Objectives: Vitamin D is recognized as a key modulator of metabolic diseases, including metabolic-dysfunction-associated steatotic liver disease (MASLD), in which its deficiency contributes to both disease onset and progression. Despite the widespread and often prolonged use of vitamin D supplementation, optimal serum levels in individuals with MASLD remain unclear and warrant further investigation. Methods: In this study, hepatic steatosis was induced in male and female Wistar rats over a 45-day period. The animals were then divided into five groups (control, 2500, 7000, 14,000, and 21,000 IU/kg/week of cholecalciferol). After four weeks of treatment, the animals were euthanized, and blood samples were collected for biochemical, hormonal, inflammatory, oxidative stress analyses and liver architecture evaluation. Results: High-dose vitamin D supplementation in rats with MASLD induced dose-dependent metabolic, inflammatory, and oxidative changes, with some sex-specific differences. Urea and alanine aminotransferase levels increased at higher doses in both sexes, suggesting potential nephrotoxic and hepatotoxic effects, while creatinine and aspartate aminotransferase remained stable. Adiponectin levels decreased consistently, and leptin levels rose across all doses, indicating a shift toward a pro-adipogenic profile. Pro-inflammatory molecules (IL-1β, IL-6, IL-8, TNF, C-reactive protein) increased progressively with dose, while IL-10 followed a U-shaped curve. Oxidative stress markers showed elevated protein carbonylation only at the highest dose, a slight reduction in TBARS, and a peak in total antioxidant status at 7000 IU/kg/week. Conclusions: High-dose vitamin D triggers antioxidant responses but drives harmful inflammatory and metabolic shifts in MASLD. Full article

The utilization of oil sludge for the creation of value-added petroleum products represents an important research direction, as certain processing routes do not incur the additional costs that are associated with more complex refining operations. The selection of the most appropriate treatment method is therefore critical for achieving cost-effective processing outcomes. The economic feasibility of a particular technology is largely determined by the physical–chemical properties and potential toxicity of oil sludge, and thus, it is essential to comprehensively characterize and assess the toxicity of this substance. In this study, the physical–chemical composition and principal characteristics of oil sludge obtained from a Kazakhstan oil company were examined. To clean the oil sludge, an alkaline solution was used as a surfactant with a solid–liquid ratio of 1:3. The solid content in the sludge was reduced from 23% to 0.76%. The results revealed that the hydrocarbon fraction of the oil sludge was predominantly composed of heavy fractions. In addition, the effects of thermal parameters on treatment efficiency were found to contribute to the secondary products present in high oil fractions. Treatment with inert gases improved processing efficiency rates by over 57%. The most efficient results included the pyrolysis of cleaned oil sludge with minimum solid residues (5.8% under CO₂) and maximum gas products (37.8% under N₂). Full article

Background: Recent research has focused on diet as a potential source of antioxidants in the context of both human health and disease prevention. Among the many plant-derived antioxidants, sulforaphane (SFN) has emerged as a potent phytochemical in the recent literature for sustaining health and combating cancerous, inflammatory, and neurodegenerative diseases. Thus, the market for supplements and functional foods has been quick to adapt to this new market niche. We aimed to investigate the phytochemical profile of broccoli sprouts and evaluate their antioxidant capacity through biochemical assays. Methods: UHPLC and MS/MS were used to analyse the phytochemical characteristics of broccoli sprout extracts. Antioxidant tests, including the DPPH test, ferrous iron chelation, hydroxyl radical neutralisation, and lipoxygenase inhibition, were used to evaluate their antioxidant potential. Results: The broccoli sprout extracts emerged as an adequate source of SFN, as well as other biologically active compounds such as xanthorhamnin. Moreover, biochemical assays showcased their antioxidant capacity. Conclusions: Broccoli sprouts could constitute an important source of dietary antioxidants with high bioavailability and high accessibility, helping sustain health and even combat various diseases. Full article

The accumulation of dead wood can serve as a potential source of insect pests, with scolytids being the most frequently discussed group. The aim of this study was to quantify the abundance and species composition of scolytids and their natural saproxylic beetle enemies in a beech reserve. In addition, we compared the types of dead wood preferred by scolytids and their natural enemies. Beetles were sampled passively using window traps, which effectively capture the actual density of beetles within the stand. In total, 20,515 saproxylic beetles were collected; the analyses included 11 scolytids species with 3017 individuals and 51 species of natural enemies with 4976 individuals. The results revealed a significantly higher abundance of natural saproxylic beetle enemies, with no strong affiliation to specific types of dead wood. This may indicate a high mobility of natural enemies actively searching for food resources within the forest stands. In conclusion, beech reserves support high abundances of natural scolytid enemies that exceed the numbers of scolytids themselves, indicating effective natural control processes. Full article

The discovery of novel marine natural products and their sustainable application continue to be vital focuses in marine biological research. The aim of this study is to investigate the inhibitory effect of the compound 5Z-7-Oxozeaenol isolated from the fungus Curvularia sp. MDCW-1060 on the proliferation of MDA-MB-231 cells and its molecular mechanism. A series of functional assays, including 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, Transwell migration, and colony formation, were employed to evaluate the effects of 5Z-7-Oxozeaenol on cellular viability, apoptosis, migration, and clonogenicity. The RNA sequencing (RNA-seq) coupled with bioinformatic analysis was conducted to identify affected differentiated gene expression and signaling pathways. The molecular docking was performed to predict potential protein targets, and Western blot was used to validate expression and phosphorylation levels of key signaling molecules. The results demonstrated that 5Z-7-Oxozeaenol significantly suppressed proliferation and migration while promoting apoptosis in MDA-MB-231 cells. The transcriptomic analysis indicated enrichment in pathways related to cancer, cytokine–cytokine receptor interaction, MAPK and PI3K-Akt signaling, and cell adhesion molecules. The molecular docking suggested a high binding affinity between 5Z-7-Oxozeaenol and PTPRN. While Western blot analysis confirmed the downregulation of phosphorylated FAK, PI3K, Akt, and MAPK, along with reduced cyclin D1 expression. Additionally, 5Z-7-Oxozeaenol upregulated the pro-apoptotic proteins p53 and cleaved caspase-3. In conclusion, 5Z-7-Oxozeaenol exerts potent antitumor effects on MDA-MB-231 cells through multi-pathway inhibition and induction of apoptosis, highlighting its potential as a marine-derived therapeutic candidate for breast cancer treatment. Full article

Milk is widely consumed due to its high nutritional value and ease of digestion. However, because it is highly perishable, it requires specific technologies to ensure its microbiological safety and preserve its characteristics. Thermal methods such as pasteurization and UHT are common, but the growing demand for more natural foods is driving interest in less invasive alternatives. This study reviews emerging technologies in milk processing, such as freeze-drying, ultrasound, supercritical carbon dioxide, ohmic heating, pulsed electric fields, high pressure, ozonation, cold plasma, and pulsed light. These methods show potential for eliminating microorganisms with reduced nutritional loss and environmental impact. Despite advances, challenges remain for their large-scale application, especially in process standardization and economic viability. This analysis contributes to expanding knowledge about these technologies, offering pathways for innovation, sustainability, and greater alignment with today’s consumer demands. Full article

Background: Perforation of the piriform sinus is a rare but severe clinical event that can lead to cervico-thoracic mediastinitis, a life-threatening condition requiring urgent multidisciplinary intervention. Among its etiologies, accidental ingestion of foreign bodies, including dental prostheses, is uncommon but poses significant risks due to the anatomical vulnerability of the hypopharyngeal structures. Methods: We report a rare case of right piriform sinus perforation secondary to the ingestion of a dental prosthesis, complicated by cervico-mediastinitis, sepsis, tracheostomy, and sacral pressure ulcer. The clinical course required emergency surgical intervention and intensive supportive care. Results: A novel aspect of this case was the use of the Endoscopic Vacuum-Assisted Closure (EVAC) irrigation system as an adjunctive technique in the management of deep cervical drainage. Rather than approaching the fistula from within the lumen, the team created a controlled external drainage system, adaptation of the vacuum-assisted closure therapy directly over the fistulous tract. Conclusions: This case highlights the importance of early diagnosis, high clinical suspicion and coordinated management in the treatment of piriform sinus perforations. It also illustrates the potential applicability of modern technologies such as negative pressure irrigation in the complex management of deep neck infections and mediastinitis. Full article

The performance and longevity of next-generation nuclear reactors depend on the implementation of sensing technologies able to withstand extreme conditions. This study evaluates the performance of femtosecond-laser-inscribed Fiber Bragg Grating (fs-FBG) sensors under simulated startup low-power conditions representative of newcleo’s Generation IV Lead-cooled Fast Reactors (LFRs). The primary goal of this preliminary test phase is to validate the suitability of fs-FBG sensors for high-temperature (300 °C) and mechanical stress (16–80 MPa cyclic tensile stress) monitoring, emphasizing their reliability and accuracy. The experimental campaign involved rigorous thermal and thermo-mechanical testing, conducted in compliance with ASTM standards, to assess key performance metrics such as linearity, repeatability, and precision. The results demonstrate that fs-FBG sensors deliver consistent and reliable measurements in extreme environments, with a temperature sensitivity of 12.62 pm/°C and a displacement sensitivity of 3.95 nm/mm. These findings provide a strong basis for the use of fs-FBG sensors in Generation IV nuclear reactors, highlighting their potential as advanced tools for structural health monitoring. Full article