Search Results (824)

Retrotransposons exhibit increased activity in cancer cells. One possible approach to anticancer therapy is to use this activity to influence the energy balance in cells. Abnormal distribution of retrotransposons in the genome requires additional energy consumption, which can lead to a significant decrease in the total amount of free ATP molecules in the cell. A decrease in ATP levels below a certain threshold can in turn trigger a cell death program. To investigate the possibility of such a scenario, we developed a mathematical model of the cellular energy balance that describes the dynamics of energy consumption by the main cellular processes, including costs of retrotransposon activity. The model considers changes in the concentrations of ATP, active retrotransposons (LINE-1 and SINE) in the human genome, as well as mRNAs and proteins that are expression products of retrotransposon and constitutive genes. We estimated the parameter values in the model based on literature data and numerical optimization. We found a single stable stationary solution, characterized by low retrotransposon activity, and used it as the reference steady state for further analysis. Parametric sensitivity analysis revealed the parameters whose changes had the greatest impact on cellular ATP levels. The LINE-1 deactivation rate constant and the maximum LINE-1 transcription rate were the most sensitive among the transposon-related parameters. Perturbation of these parameters led to a decrease in the number of free ATP to 30% of the reference value and below. Transcription of retrotransposons under perturbed parameters became comparable to the translation of constitutive genes in terms of energy costs. The presented results indicate that cancer cell death can be initiated by increasing the load on the energy balance due to the activation of transposons. Full article

Objectives: Silodosin, a selective α1A-adrenoceptor antagonist, is used to treat lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Genetic polymorphisms in drug-metabolizing enzymes and transporters may contribute to interindividual variability in its efficacy and safety. This study aimed to investigate the influence of CYP3A4, CYP3A5, UGT2B7, and ABCB1 polymorphisms on silodosin pharmacokinetics, efficacy, and safety in Russian patients with BPH. Methods: A prospective observational study included 103 Russian male patients with moderate-to-severe LUTS (IPSS > 8) due to BPH, treated with silodosin (8 mg daily) for 8 weeks. Genotyping for CYP3A4*1B, CYP3A4*22, CYP3A5*3, UGT2B7 (rs73823859, rs7439366, and rs7668282), and ABCB1 (rs4148738, rs1045642, rs2032582, and rs1128503) was performed using real-time PCR. The silodosin minimum steady-state plasma concentration (Css min) was measured via HPLC-MS. Efficacy was evaluated by the International Prostate Symptom Score (IPSS), quality of life scale, maximum urinary flow rate (Qmax), residual urine volume (RUV), and prostate volume at the baseline and week 8. Adverse drug reactions (ADRs) were recorded. Results: CYP3A4*22 CT carriers (n = 6) exhibited higher Css min (17.59 ± 2.98 vs. 9.0 ± 10.47 ng/mL, p = 0.049) but less absolute IPSS improvement (p < 0.05), likely due to higher baseline symptom severity. However, the change in IPSS (ΔIPSS_1–4) from the baseline to week 8 did not differ significantly (−5.78 ± 5.29 vs. −6.0 ± 4.54, p = 0.939). CYP3A5*3 GG homozygotes (n = 96) showed greater ΔIPSS_1–4 improvement (−6.25 ± 4.60 vs. 0.0 ± 9.53, p = 0.042) and a lower IPSS at day 28 (7.64 ± 4.50 vs. 20.0 ± 6.55, p < 0.001). UGT2B7 rs7439366 TT carriers (n = 34) had an improved Qmax (ΔQmax_1–4 5.4 vs. 3.3 and 2.0 mL/s for CC and CT, p = 0.041). ABCB1 1236C>T TT homozygotes (n = 25) showed a trend toward reduced RUV (p = 0.053). No polymorphisms were associated with adverse drug reactions (15 events in 42 patients, 35.7%). Conclusions: Genetic polymorphisms CYP3A4*22, CYP3A5*3, and UGT2B7 rs7439366 may modulate silodosin pharmacokinetics and efficacy parameters in BPH patients but not safety. Larger-scale studies are warranted to validate these initial findings. Full article

Since 2000, antioxidant research in Chile has shown steady growth, from the chemical sciences to their application in biomedical sciences, functional foods, reproduction, and environmental studies. This study presents a bibliometric analysis of Chilean scientific output in the field of antioxidants from 2000 to 2024, organized into five-year intervals. A total of 3190 research articles indexed in the Web of Science (WoS) database were analyzed. Bibliometric indicators—including Price’s, Bradford’s, and Zipf’s laws—were applied to assess literature growth, authorship concentration, journal dispersion, and keyword evolution. Key findings include (i) high productivity from institutions such as the Universidad de Chile, Pontificia Universidad Católica de Chile, Universidad de Santiago de Chile, and Universidad de Concepción; (ii) the identification of leading authors such as Dr. Antonio Vega-Gálvez, Dr. Guillermo Schmeda-Hirschman, and Dr. Mario J. Simirgiotis; and (iii) the consolidation of three main research areas: biomedical applications (e.g., cancer, cardiovascular, and neurodegenerative diseases), food science and technology (e.g., antioxidant properties, and agro-industrial waste revalorization), and ethnopharmacology (e.g., native plant use). This study made it possible to map the state of the art of antioxidant research in Chile and identify key players and research lines, consolidating a comprehensive vision of scientific development in this field. Full article

This study aimed to examine the pharmacokinetic changes in tolfenamic acid administered intravenously and orally to ducks at different doses (2, 4, and 8 mg/kg). Furthermore, the binding ratio to plasma proteins was assessed utilizing the ultrafiltration method. Eighteen male Pekin ducks were randomly assigned to three dosage groups (2, 4, and 8 mg/kg), with each group undergoing a trial in two phases: intravenous (IV) and oral administration. The sample was analyzed using an approved HPLC-UV method. A non-compartmental analysis was utilized to evaluate the pharmacokinetic data. For 2 mg/kg IV injection, the area under the curve from zero to infinity (AUC_0-∞), total clearance (Cl_T), volume of distribution at steady state (V_dss), and elimination half-life (t_1/2ʎz) were 13.03 h*µg/mL, 0.15 L/h/kg, 0.30 L/kg, and 1.72 h, respectively. Following oral administration at a dose of 2 mg/kg, the AUC_0-∞, peak plasma concentration (C_max), and bioavailability were 6.32 h*µg/mL, 2.25 µg/mL, and 48.52%, respectively. The t_1/2ʎz was extended, C_max and AUC_0-∞ elevated, T_max shortened, and Cl_T decreased in a dose-dependent manner. No dose-related change was observed in V_dss and bioavailability. In ducks, tolfenamic acid’s plasma protein binding was 99.74%, unaffected by concentration. These results may contribute to the application of tolfenamic acid in ducks at different doses, but dose-related changes in therapeutic efficacy should also be demonstrated. Full article

Humidity and oxygen have significant impacts on the accuracy of hydrogen detection, especially for metal oxide semiconductor sensors at room temperature. Addressing this challenge, this study employs a screen-printed 1 × 2 resistive sensor array made from an identical 1 wt.% platinum-modified tin oxide nanoparticle material. Fabrication variability between the two sensing elements was intentionally leveraged to enhance array output differentiation and information content. Systematic hydrogen-sensing tests were conducted on the array under diverse oxygen and moisture conditions. Three distinct feature types—the steady-state value, resistance change, and area under the curve—were extracted from the output of each array element. These features, integrated with their quotient, formed a nine-feature vector matrix. A multiple linear regression model based on this array output was developed and validated for hydrogen prediction, achieving a coefficient of determination of 0.95, a mean absolute error of 125 ppm, and a mean relative standard deviation of 7.07%. The combined information of the array provided significantly more stable and precise hydrogen concentration predictions than linear or nonlinear models based on individual sensor features. This approach offers a promising path for mass-producing highly interference-resistant, precise, and stable room-temperature hydrogen sensor arrays. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article

The electromechanical braking (EMB) system is an important component of intelligent vehicles and is also the core actuator for longitudinal dynamic control in autonomous driving motion control. Therefore, we propose a new mechanism layout form for EMB and a feedforward second-order linear active disturbance rejection controller based on clamping force. This solves the problem of excessive axial distance in traditional EMB and reduces the axial distance by 30%, while concentrating the PCB control board for the wheels on the EMB housing. This enables the ABS and ESP functions to be integrated into the EMB system, further enhancing the integration of line control and active safety functions. A feedforward second-order linear active disturbance rejection controller (LADRC) based on the clamping force of the brake caliper is proposed. Compared with the traditional clamping force control methods three-loop PID and adaptive fuzzy PID, it improves the response speed, steady-state error, and anti-interference ability. Moreover, the LADRC has more advantages in parameter adjustment. Simulation results show that the response speed is increased by 130 ms, the overshoot is reduced by 9.85%, and the anti-interference ability is increased by 41.2%. Finally, the feasibility of this control algorithm was verified through the EMB hardware-in-the-loop test bench. Full article

In view of the problems of slow heat storage process and uneven temperature distribution in the existing phase change heat accumulator, a new type of mesh fin heat accumulator was designed and developed which increased the contact area between the phase change material (PCM) and the fins, enhanced the apparent thermal conductivity of the PCM, improved the heat storage efficiency of the heat accumulator, blocked the PCM, improved the natural convection erosion of the PCM on the upper and lower parts of the heat accumulator, and melted the PCM in each area more evenly. Fluent15.0 was used to numerically simulate the heat storage process of the mesh fins heat accumulator with the finite volume method. The composite PCM prepared by adding 10% mass fraction of expanded graphite to paraffin wax was used as the heat storage material. A 2D, non-steady-state model, incompressible fluid, and the pressure-based solution method were selected. The energy model and the solidification and melting model based on the enthalpy method were used to simulate and calculate the phase change process of PCM. The PISO algorithm was used. The influences of the structural parameters of the mesh fins on the heat storage condition of the heat accumulator were investigated by numerical simulation. The results showed that with the increase in the radius R of the mesh fin, the heat storage time decreased first and then increased. With the increases in vertical fin thickness c, mesh fins thickness δ, and vertical fins number N, the heat storage time decreased. The optimal mesh fin structure parameters were R = 33.5 mm, c = 3 mm, δ = 3 mm, and N = 8, and the heat storage time was 8086 s, which is 47.8% shorter than that of the concentric tube heat accumulator. Otherwise, with the increases in vertical fin thickness c, mesh fins thickness δ, and vertical fins number N, the PCM volume decreased, which shortened PCM melting time. Full article

Blood analogs are widely employed in in vitro experiments such as particle image velocity (PIV) to secure hemodynamics, assisting pathophysiological diagnoses of neurovascular and cardiovascular diseases, as well as pre-surgical planning and intraoperative orientation. To obtain accurate physical parameters, which are critical for diagnosis and treatment, blood analogs should exhibit realistic non-Newtonian shear-thinning features. In this study, two types of blood analogs working under room temperature (293.15 K) were created to mimic the steady-state shear-thinning features of blood over a temperature range of 295 to 312 K and a shear range of 1~250 s⁻¹ at a hematocrit of ~40%. Type I was a general-purpose analog composed of deionized (DI) water and xanthan gum (XG) powder, while Type II was specially designed for PIV tests, incorporating DI water, XG, and fluorescent microspheres. By minimizing the root mean square deviation between generated blood analogs and an established viscosity model, formulas for both blood analogs were successfully derived for the designated temperatures. The results showed that both blood analogs could replicate the shear-thinning viscosities of real blood, with the averaged relative discrepancy < 5%. Additionally, a strong linear correlation was observed between body temperature and XG concentration in both blood analogs (coefficient of determination > 0.96): for Type I, 295–312 K correlates with 140–520 ppm, and for Type II, 295–315 K correlates with 200–560 ppm. This work bridges the gap between idealized steady-state non-Newtonian viscosity models of blood and the complexities of real-world physiological conditions, offering a versatile platform for advancing particle image velocimetry tests and hemodynamics modeling, optimizing therapeutic interventions, and enhancing biomedical technologies in temperature-sensitive environments. Full article

The non-monotonic behavior of amperometric enzyme-based biosensors under uncompetitive and noncompetitive (mixed) substrate inhibition is investigated computationally using a two-compartment model consisting of an enzyme layer and an outer diffusion layer. The model is based on a system of reaction–diffusion equations that includes a nonlinear term associated with non-Michaelis–Menten kinetics of the enzymatic reaction and accounts for the partitioning between layers. In addition to the known effect of substrate inhibition, where the maximum biosensor current differs from the steady-state output, it has been determined that external diffusion limitations can also cause the appearance of a local minimum in the current. At substrate concentrations greater than both the Michaelis–Menten constant and the uncompetitive substrate inhibition constant, and in the presence of external diffusion limitation, the transient response of the biosensor, after immersion in the substrate solution, may follow a five-phase pattern depending on the model parameter values: it starts from zero, reaches a global or local maximum, decreases to a local minimum, increases again, and finally decreases to a steady intermediate value. The biosensor performance is analyzed numerically using the finite difference method. Full article

This study presents an analytical and experimental approach to enhance cantilever-based piezoelectric energy harvesters by optimizing thickness distribution. Using a gradient projection algorithm within a state-space framework, the unimorph beam’s geometry is tailored while constraining the first natural frequency. The objective is to amplify axial strain within the piezoelectric layers, thereby increasing electric polarization and maximizing the conversion efficiency of mechanical vibrations into electrical energy. The steady-state response under harmonic base excitation at resonance was modeled to evaluate the harvester’s dynamic behavior against uniform-thickness counterparts. Results show that the optimized beam achieves significantly higher output voltage and energy harvesting efficiency. Simulations reveal effective strain concentration in regions of high piezoelectric sensitivity, enhancing power generation under resonant conditions. Two independent experimental setups were employed for empirical validation: a non-contact laser vibrometry system (Polytec 3D) and a first resonant base excitation setup. Eigenfrequencies matched within 5% using a Polytec multipath interferometry system, and constant excitation tests showed approximately 30% higher in optimal shapes electrical potential value generation. The outcome of this study highlights the efficacy of geometric tailoring—specifically, non-linear thickness shaping—as a key strategy in achieving enhanced energy output from piezoelectric harvesters operating at their fundamental frequency. This work establishes a practical route for optimizing unimorph structures in real-world applications requiring efficient energy capture from low-frequency ambient vibrations. Full article

With water availability being one of the world’s major challenges, this study aims to propose a Zero Liquid Discharge (ZLD) system for treating saline effluents from an urban wastewater treatment plant (UWWTP), thereby supplementing into the existing water cycle. The system, which employs membrane (nanofiltration and reverse osmosis) and thermal technologies (multi-effect distillation evaporator and vacuum crystallizer), has been installed and operated in Cyprus at Larnaca’s WWTP, for the desalination of the tertiary treated water, producing high-quality reclaimed water. The nanofiltration (NF) unit at the plant operated with an inflow concentration ranging from 2500 to 3000 ppm. The performance of the installed NF90-4040 membranes was evaluated based on permeability and flux. Among two NF operation series, the second—operating at 75–85% recovery and 2500 mg/L TDS—showed improved membrane performance, with stable permeability (7.32 × 10⁻¹⁰ to 7.77 × 10⁻¹⁰ m·s⁻¹·Pa⁻¹) and flux (6.34 × 10⁻⁴ to 6.67 × 10⁻⁴ m/s). The optimal NF operating rate was 75% recovery, which achieved high divalent ion rejection (more than 99.5%). The reverse osmosis (RO) unit operated in a two-pass configuration, achieving water recoveries of 90–94% in the first pass and 76–84% in the second. This setup resulted in high rejection rates of approximately 99.99% for all major ions (Cl⁻, Na⁺, Ca²⁺, and Mg²⁺), reducing the permeate total dissolved solids (TDS) to below 35 mg/L. The installed multi-effect distillation (MED) unit operated under vacuum and under various inflow and steady-state conditions, achieving over 60% water recovery and producing high-quality distillate water (TDS < 12 mg/L). The vacuum crystallizer (VC) further concentrated the MED concentrate stream (MEDC) and the NF concentrate stream (NFC) flows, resulting in distilled water and recovered salts. The MEDC process produced salts with a purity of up to 81% NaCl., while the NFC stream produced mixed salts containing approximately 46% calcium salts (mainly as sulfates and chlorides), 13% magnesium salts (mainly as sulfates and chlorides), and 38% sodium salts. Overall, the ZLD system consumed 12 kWh/m³, with thermal units accounting for around 86% of this usage. The RO unit proved to be the most energy-efficient component, contributing 71% of the total water recovery. Full article

Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and outcomes. This study aimed to characterize the whole blood gene expression profile of Bahraini SCD patients, identifying differentially expressed genes during steady-state (n = 10) and VOC (n = 10) compared to healthy controls (n = 8). Analysis revealed 2073 and 3363 dysregulated genes during steady-state and VOC, respectively, compared to controls, with 1078 genes differentially expressed during VOC versus steady-state. Gene Ontology (GO) enrichment analysis highlighted significant deregulation in immune and hematopoietic pathways, including down-regulation of critical genes for immune modulation and hematopoietic balance. Notably, the transcription factor RUNX3, involved in immune cell differentiation and inflammation, was among the 668 down-regulated genes. RUNX3 was four-fold down-regulated in microarray analysis, three-fold in PCR, and showed a mean protein concentration of 11.13 pg/mL during VOC compared to 457.93 pg/mL during steady-state (p < 0.01). These findings suggest that RUNX3 may serve as a potential biomarker for VOC. Future large-scale validation, additional proteomic studies, and functional investigations are recommended to confirm its clinical utility and significance. Full article

For the gas injection process in the underground natural gas storage, it is of great significance to separate lubricating oil droplets from natural gas to ensure the capacity of gas injection. However, the interaction mechanism, among various factors, is still unclear in real field conditions. In this study, the filtration performances of filter elements were investigated in a range of gas temperatures from 20 °C to 70 °C, aerosol concentrations from 400 mg/m³ to 1200 mg/m³ and flowrates from 37.2 m³/h to 74.4 m³/h. The results show that at the same flowrate, the steady-state filtration efficiency decreases with increasing temperature, resulting from a shift in the upstream aerosol towards the smaller size and an increase in the concentration for droplets within the range of 0.3 to 2 μm. The filtration efficiency only increases by 0.02% at 20 °C, while the steady-state efficiency increases by more than 0.10% at 70 °C and all the flowrates. At the same gas temperature and aerosol concentration, the steady-state filtration efficiency increases with the increase in flowrate. In practical applications, the filtration performance can be improved by lowing the gas temperature, setting up fewer filter elements in the separator, and appropriately reducing the injection amount of lubricating oil. Full article

Background/Objectives: In the context of diabetes, a multifactorial metabolic disorder with significant clinical implications, the present study investigates the hypoglycemic effects of a synthetic sulfonamide (S) administered individually and in combination with Salvia officinalis extract, compared to metformin as a standard therapeutic agent. Methods: An in vivo model of experimentally induced diabetes using alloxan was applied to Wistar female rats, divided into six experimental groups, including a healthy control group and a diabetes-induced, untreated group. Plasma concentrations of metformin and sulfonamide were quantified by high-performance liquid chromatography. The plasma steady-state concentrations of the pharmaceutical agents and their correlation with hypoglycemic effect were evaluated. Results: The combination of the synthetic sulfonamide (S) with Salvia officinalis extract resulted in the greatest reduction in blood glucose level (average value of 50.2%) compared to S (40.6%) or metformin (36.4%). All treatments demonstrated statistically significant differences in blood glucose levels compared to the diabetes-induced untreated group (p < 0.05). Pharmacokinetic analysis revealed a larger volume of distribution for the synthetic sulfonamide S (23.92 ± 8.40 L) compared to metformin (16.07 ± 5.60 L), consistent with its physicochemical properties. No significant correlation was found between plasma drug levels and glycemic response (p > 0.05). Conclusions: Our findings support the potential of combining standard therapeutic agents with natural alternatives such as Salvia officinalis to achieve improved glycemic control through complementary mechanisms. To the best of our knowledge, this is the first in vivo study to evaluate the combined effects of a sulfonylurea-type compound and Salvia officinalis extract in a diabetic animal model. Full article