Search Results (2,299)

Recently, a number of natural biologically active substances have been proven to be attractive alternatives to conventional anticancer medicine or as adjuvants in contemporary combination therapies. Although lignin-based materials were previously accepted as waste materials with limited usefulness, recent studies increasingly report the possibility of their use for novel applications in various industrial branches, including biomedicine. In this regard, the safety, efficiency, advantages and limitations of lignin compounds for in vitro/in vivo applications remain poorly studied and described. This study was carried out to investigate the possibility of using newly synthesized, alkali lignin-based micro-/nano-biopolymer formulations (Lignin@Formulations/L@F) as carriers for substances with antioxidant and/or anticancer effectiveness. Moreover, we tried to assess the opportunity for using an electro-assisted approach for achieving improved intracellular internalization. An investigation was conducted on an in vitro panel of breast cell lines, namely two breast cancer lines with different metastatic potentials and one non-tumorigenic line as a control. The characterization of all tested formulations was performed via DLS (dynamic light scattering) analysis. We developed an improved separation procedure via size/charge unification for all types of Lignin@Formulations. Moreover, in vitro applications were investigated. The results demonstrate that compared to healthy breast cells, both tested cancer lines exhibited slight sensitivity after treatment with different formulations (empty or loaded with antioxidant substances). This effect was also enhanced after applying electric pulses. L@F loaded with Quercetin was also explored only on the highly metastatic cancer cell line as a model for the breast cancer type most aggressive and non-responsive to traditional treatments. All obtained data suggest that the tested formulations have potential as carriers for the electro-assisted delivery of natural antioxidants such as Quercetin. Full article

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

Background/Objectives: The simulation of human movement offers transformative potential for the design of medical devices, particularly in understanding the cause–effect dynamics in individuals with neurological or musculoskeletal impairments. This study presents a simulation-driven framework to determine the optimal ankle–foot orthosis (AFO) stiffness for mitigating the risk of ankle sprains due to excessive subtalar inversion during high-impact activities, such as landing from a free fall. Methods: We employed biomechanical simulations to assess the influence of translational stiffness on subtalar inversion control, given that inversion angles exceeding 25 degrees are strongly correlated with injury risk. Simulations were conducted using a musculoskeletal model with and without a passive AFO; the stiffness varied in three anatomical directions. A Design of Experiments (DoE) approach was utilized to capture nonlinear interactions among stiffness parameters. Results: The results indicated that increased translational stiffness significantly reduced inversion angles to safer levels, though direction–dependent effects were noted. Based on these insights, we developed a 4D visualization tool that integrates simulation data with an interactive color–coded interface to depict ”safe design” zones for various AFO stiffness configurations. This tool supports clinicians in selecting stiffness values that optimize both safety and functional performance. Conclusions: The proposed framework enhances clinical decision-making and engineering processes by enabling more accurate and individualized AFO designs. Full article

Background: The use of lower limb prosthesis can impact all aspects of daily life, activities and participation. Various studies have compared the microprocessor-controlled knee (MPK) to the non-microprocessor-controlled knee (NMPK) using a variety of different outcome measures, but results are inconsistent and raise the question of which type of knee is most effective. Therefore, we aimed to assess the effect of MPKs compared to NMPKs across all classified ICF domains in adult prosthesis users. Methods: Participants performed baseline measurements with the NMPK (T0). One week later, they started a four-to-six-week trial period with the MPK. Afterward, measurements were repeated with the MPK (T1). Functional tests (6MWT, TUG-test and activity monitor) and questionnaires (ABC, SQUASH, USER-P and PEQ) were used. For statistical analyses, paired t-tests, Wilcoxon signed-rank tests and Chi² test were applied. The Benjamini–Hochberg procedure was applied to correct for multiple testing. Results: Twenty-five participants were included. Using an MPK compared to an NMPK significantly resulted in improvements in balance and walking confidence, safety, walking distance and self-reported walking ability, as well as a decrease in number of stumbles and falls. Additionally, participants using an MPK were significantly more satisfied with their participation, experienced fewer restrictions, reported greater satisfaction with the appearance and utility of the MPK, experienced less social burden and reported better well-being, compared to using an NMPK. Conclusions: Using an MPK instead of an NMPK can lead to significant improvements in all classified ICF domains, such as improved walking ability, confidence and satisfaction and reduced fall risk. Full article

UV-C irradiation is an innovative postharvest technique for increasing the safety of fruits and vegetables. This study investigated the effect of UV-C rays (UV-C1 = 0.26 KJ/m²; UV-C2 = 0.40 KJ/m²; UV-C3 = 0.67 KJ/m²; and UV-C4 = 1.34 KJ/m²) on the preservation of the antioxidants, hardness, and color of fresh green asparagus during storage. UV-C1 and UV-C2 significantly maintained higher total phenolic content (10.6%), total flavonoid content (36%), rutin (14.3%), quercetin (27.03%), kaempferol-3-O-rutinoside (21.25%), and antioxidant activity (DPPH 7.5%). Over three weeks of storage, quercetin, ferulic acid, and kaempferol 3-O-rutinoside increased, while rutin and caffeic acid decreased. Storage caused a significant change in the color and hardness of the control sample, but UV-C4 counteracted hardening for up to three weeks, and UV-C3 was the best dose for stabilizing color during storage. This study indicates that the choice of UV-C dose can be modulated based on the characteristics that are intended to be preserved in green asparagus, maintaining a balance between nutraceutical and hedonic characteristics. To maintain the maximum level of nutraceutical compounds over time, UV-C2 can be adopted, while to preserve texture and color, UV-C3 and UV-C4 are a better choice. Full article

Sensor fusion in intelligent suspension systems constitutes a fundamental technology for optimizing vehicle dynamic stability, ride comfort, and occupant safety. By integrating data from multiple sensor modalities, this study proposes a hierarchical multi-sensor fusion framework for active suspension control, aiming to enhance control precision. Initially, a binocular vision system is employed for target detection, enabling the identification of lane curvature initiation points and speed bumps, with real-time distance measurements. Subsequently, the integration of Global Positioning System (GPS) and inertial measurement unit (IMU) data facilitates the extraction of road elevation profiles ahead of the vehicle. A BP-PID control strategy is implemented to formulate mode-switching rules for the active suspension under three distinct road conditions: flat road, curved road, and obstacle road. Additionally, an ant colony optimization algorithm is utilized to fine-tune four suspension parameters. Utilizing the hardware-in-the-loop (HIL) simulation platform, the observed reductions in vertical, pitch, and roll accelerations were 5.37%, 9.63%, and 11.58%, respectively, thereby substantiating the efficacy and robustness of this approach. Full article

Diabetic sensorimotor polyneuropathy (DSPN) is the most prevalent complication of diabetes, affecting nearly half of all persons with diabetes. It is characterized by nerve degeneration, progressive sensory loss and pain, with increased risk of ulceration and amputation. Despite its high prevalence, disease-modifying treatments for DSPN do not exist. Mitochondrial dysfunction and Ca²⁺ dyshomeostasis are key contributors to the pathophysiology of DSPN, disrupting neuronal energy homeostasis and initiating axonal degeneration. Recent findings have demonstrated that antagonism of the muscarinic acetylcholine type 1 receptor (M₁R) promotes restoration of mitochondrial function and axon repair in various neuropathies, including DSPN, chemotherapy-induced peripheral neuropathy (CIPN) and HIV-associated neuropathy. Pirenzepine, a selective M₁R antagonist with a well-established safety profile, is currently under clinical investigation for its potential to reverse neuropathy. The transient receptor potential melastatin-3 (TRPM3) channel, a Ca²⁺-permeable ion channel, has recently emerged as a downstream effector of G protein-coupled receptor (GPCR) pathways, including M₁R. TRPM3 activation enhanced mitochondrial Ca²⁺ uptake and bioenergetics, promoting axonal sprouting. This review highlights mitochondrial and Ca²⁺ signaling imbalances in DSPN and presents M₁R antagonism and TRPM3 activation as promising neuro-regenerative strategies that shift treatment from symptom control to nerve restoration in diabetic and other peripheral neuropathies. Full article

This study investigated the immunonutritional potential of high-molecular-weight (Mw~85 kDa), non-degraded chitosan (NCS) and gamma-radiation-degraded, low-molecular-weight chitosan (RCS) incorporated into aquafeeds for Nile tilapia (Oreochromis niloticus). RCS was produced by γ-irradiation (10 kGy) in the presence of 0.25% (w/v) H₂O₂, yielding low-viscosity, colloidally stable nanoparticles with Mw ranging from 10 to 13 kDa. Five diets were formulated: a control, NCS at 0.50%, and RCS at 0.025%, 0.050%, and 0.075%. No adverse effects on growth were observed, confirming safety. Immune gene expression (e.g., ifng1, nfκb, tnf), antioxidant markers (e.g., reduced MDA, increased GSH and GR), and nonspecific humoral responses (lysozyme, IgM, and bactericidal activity) were significantly enhanced in the NCS-0.50, RCS-0.050, and RCS-0.075 groups. Notably, these benefits were achieved with RCS at 10-fold lower concentrations than NCS. Following challenge with Edwardsiella tarda, fish fed RCS-0.050 and RCS-0.075 diets exhibited the highest survival rates and relative percent survival, highlighting robust activation of innate and adaptive immunity alongside redox defense. These results support the use of low-Mw RCS as a biologically potent, cost-effective alternative to traditional high-Mw chitosan in functional aquafeeds. RCS-0.050 and RCS-0.075 show strong potential as immunonutritional agents to enhance fish health and disease resistance in aquaculture. Full article

Since the onset of the COVID-19 pandemic, remarkable progress has been made in the development of antiviral therapies for SARS-CoV-2. Several direct-acting antivirals, such as remdesivir, molnupiravir, and nirmatrelvir/ritonavir, offer clinical benefits. These agents have significantly contributed to reducing the viral loads and duration of the illness, as well as the disease’s severity and mortality. However, despite these advances, important limitations remain. The continued emergence of resistant SARS-CoV-2 variants highlights the urgent need for adaptable and durable therapeutic strategies. Therefore, this review aims to provide an updated overview of the main antiviral strategies that are used and the discovery of new drugs against SARS-CoV-2, as well as the therapeutic limitations that have shaped clinical management in recent years. The major challenges include resistance associated with viral mutations, limited treatment windows, and unequal access to treatment. Moreover, there is an ongoing need to identify novel compounds with broad-spectrum activity, improved pharmacokinetics, and suitable safety profiles. Combination treatment regimens represent a promising strategy to increase the efficacy of treating COVID-19 while minimizing the potential for resistance. Ideally, these interventions should be safe, affordable, and easy to administer, which would ensure broad global access and equitable treatment and enable control of COVID-19 cases and preparedness for future threats. Full article

Leaves, the main by-product of lingonberry harvesting, can be effectively used as a functional feed additive due to their health-promoting properties. This study evaluated the effects of lingonberry leaf (LL) supplementation on rumen fermentation, protozoal populations, and gastrointestinal morphology in sheep. Eight one-year-old Polish Mountain Sheep ewes (mean body weight: 33 kg) were allocated to a control (basal diet; forage-to-concentrate ratio 60:40) or an experimental group (basal diet + 9.30 g/kg DM dried LLs) in a completely randomised design (n = 4 per group) over 34 days. Both diets were formulated to be isoenergetic and isonitrogenous. LL additive significantly reduced Isotrichidae protozoal counts (p < 0.001) and ruminal pectinolytic activity (p = 0.043), without altering short-chain fatty acid (SCFA) or methane concentrations (p > 0.1). Histological analyses showed increased ruminal papilla width and surface area (p < 0.001) and decreased duodenal villus height and muscular layer thickness (p < 0.01). Inflammatory lesions (reddish foci) were identified in the liver in both groups. These findings demonstrate that LL supplementation affected specific protozoal population, fibrolytic activity, and gastrointestinal morphology. Further study on a larger number of animals is recommended to validate the effects and assess the safety and efficacy of LLs as a dietary additive in ruminant nutrition. Full article

Falls are a major safety concern in physically demanding occupations such as roofing, where workers operate on inclined surfaces under unstable postures. While inertial measurement units (IMUs) are widely used in wearable fall detection systems, they often fail to capture early indicators of instability related to foot–ground interactions. This study evaluates the effectiveness of plantar pressure sensors, alone and combined with IMUs, for fall detection on sloped surfaces. We collected data in a controlled laboratory environment using a custom-built roof mockup with incline angles of 0°, 15°, and 30°. Participants performed roofing-relevant activities, including standing, walking, stooping, kneeling, and simulated fall events. Statistical features were extracted from synchronized IMU and plantar pressure data, and multiple machine learning models were trained and evaluated, including traditional classifiers and deep learning architectures, such as MLP and CNN. Our results show that integrating plantar pressure sensors significantly improves fall detection. A CNN using just three IMUs and two plantar pressure sensors achieved the highest F1 score of 0.88, outperforming the full 17-sensor IMU setup. These findings support the use of multimodal sensor fusion for developing efficient and accurate wearable systems for fall detection and physical health monitoring. Full article

Downhole kick is one of the most severe safety hazards in deep and ultra-deep well drilling operations. Traditional monitoring methods, which rely on surface flow rate and fluid level changes, are limited by their delayed response and insufficient sensitivity, making them inadequate for early warning. This study proposes a real-time monitoring technique for gas content in drilling fluid based on the attenuation principle of Ba-133 γ-rays. By integrating laboratory static/dynamic experiments and Geant4-11.2 Monte Carlo simulations, the influence mechanism of gas–liquid two-phase media on γ-ray transmission characteristics is systematically elucidated. Firstly, through a comparative analysis of radioactive source parameters such as Am-241 and Cs-137, Ba-133 (main peak at 356 keV, half-life of 10.6 years) is identified as the optimal downhole nuclear measurement source based on a comparative analysis of penetration capability, detection efficiency, and regulatory compliance. Compared to alternative sources, Ba-133 provides an optimal energy range for detecting drilling fluid density variations, while also meeting exemption activity limits (1 × 10⁶ Bq) for field deployment. Subsequently, an experimental setup with drilling fluids of varying densities (1.2–1.8 g/cm³) is constructed to quantify the inverse square attenuation relationship between source-to-detector distance and counting rate, and to acquire counting data over the full gas content range (0–100%). The Monte Carlo simulation results exhibit a mean relative error of 5.01% compared to the experimental data, validating the physical correctness of the model. On this basis, a nonlinear inversion model coupling a first-order density term with a cubic gas content term is proposed, achieving a mean absolute percentage error of 2.3% across the full range and R² = 0.999. Geant4-based simulation validation demonstrates that this technique can achieve a measurement accuracy of ±2.5% for gas content within the range of 0–100% (at a 95% confidence interval). The anticipated field accuracy of ±5% is estimated by accounting for additional uncertainties due to temperature effects, vibration, and mud composition variations under downhole conditions, significantly outperforming current surface monitoring methods. This enables the high-frequency, high-precision early detection of kick events during the shut-in period. The present study provides both theoretical and technical support for the engineering application of nuclear measurement techniques in well control safety. Full article

With ketamine gaining attention as a therapeutic drug, oral administration offers an effective alternative to traditional parenteral routes. However, a significant gap remains in understanding its use via voluntary ingestion. This preliminary study aimed to explore the feasibility of oral ketamine self-administration in mice (Mus musculus), while investigating the effects of low concentrations on the brain, liver, and kidney. Adult mice were divided into three groups and received ketamine in their drinking water for 16 days at 0 (control), 5 (K5), or 10 mg/L (K10). A transient decrease in water consumption was observed in both sexes in the K10 group; however, only females in this group showed differences in ketamine intake between groups on some days. Oxidative stress markers measured in the brain, liver, and kidney only revealed higher catalase activity in the brains of females. No significant alterations were observed in liver and kidney function in either sex, nor in inflammation, apoptosis, or DNA damage in kidney tissues. Overall, these findings support the viability of voluntary oral ketamine administration and accentuate the need to refine the proposed model, not only to prevent water consumption inhibition but also to extend the exposure period, explore potential sex-related differences in ketamine intake, and further confirm the safety of oral ketamine administration. 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

A particularly important activity carried out by railway infrastructure managers to maintain railway devices in full working order is the diagnostic process. It increases the level of railway safety. The diagnostic process involves collecting information about the equipment through inspections, tests, functional trials, parameter measurements, and analysis of the working environment, followed by comparing the obtained information with the required parameters or permissible conditions. This activity also enables the formulation of a technical diagnosis regarding the current ability of the devices to perform its intended functions, taking into account the impact of its technical condition on railway traffic safety. This is especially important in the case of railway traffic control devices, as these devices are largely responsible for ensuring railway traffic safety. The collection of data on the condition of railway traffic control devices in the form of Big Data sets and diagnostic inference is an effective factor in making operational decisions for such devices. It enables the acquisition of complete information about the actual course of the exploitation process and allows for obtaining reliable information necessary to manage this process, particularly in the areas of diagnostics forecasting of devices conditions, renewal, and organization of maintenance and repair facilities. To support this, a service data acquisition and analysis system for railway traffic control devices (SADEK) was developed. This system can serve as a software platform for maintenance needs in the railway sector. Full article