Search Results (379)

Background: Endometrial cancer (EC) is the most common gynecological malignancy, increasingly affecting premenopausal women. While hysterectomy is the standard treatment, it eliminates reproductive potential, highlighting the need for effective fertility-sparing alternatives. Current ESHRE/ESGO/ESGE guidelines recommend progestin-based therapies, often with hysteroscopic resection. However, these are based on limited pharmacological options and moderate to low-quality evidence. Novel and combination therapies have shown promise but remain absent from current clinical guidelines. This review aims to evaluate the efficacy and safety of fertility-preserving treatments for early-stage EC, emphasizing the need to update current strategies based on emerging data. Methods: A systematic review and meta-analysis will follow PRISMA guidelines and the Cochrane Handbook. Eligible studies, including randomized and non-randomized designs, will assess fertility-preserving treatments for early-stage EC. Data will be extracted on complete response, recurrence, and long-term fertility outcomes. The GRADE system will assess evidence certainty. Risk of bias will be evaluated using RoB 2 for RCTs and ROBINS-I for non-randomized studies. Meta-analysis will be performed if sufficient data are available. Conclusions: This review will provide a comprehensive analysis of fertility-sparing treatments for early-stage EC, support personalized strategies, identify evidence gaps, and guide future research. Trial registration—Prospero: CRD420251032161. Full article

Buildings are a significant component of urban space and are essential to smart cities, catastrophe monitoring, and land use planning. However, precisely extracting building polygons from remote sensing images remains difficult because of the variety of building designs and intricate backgrounds. This paper proposes an end-to-end polygon dynamic adjustment algorithm (PDAA) to improve the accuracy and geometric consistency of building contour extraction by dynamically generating and optimizing polygon vertices. The method first locates building instances through the region of interest (RoI) to generate initial polygons, and then uses four core modules for collaborative optimization: (1) the feature enhancement module captures local detail features to improve the robustness of vertex positioning; (2) the contour vertex tuning module fine-tunes vertex coordinates through displacement prediction to enhance geometric accuracy; (3) the learnable redundant vertex removal module screens key vertices based on a classification mechanism to eliminate redundancy; and (4) the missing vertex completion module iteratively restores missed vertices to ensure the integrity of complex contours. PDAA dynamically adjusts the number of vertices to adapt to the geometric characteristics of different buildings, while simplifying the prediction process and reducing computational complexity. Experiments on public datasets such as WHU, Vaihingen, and Inria show that PDAA significantly outperforms existing methods in terms of average precision (AP) and polygon similarity (PolySim). It is at least 2% higher than existing methods in terms of average precision (AP), and the generated polygonal contours are closer to the real building geometry. Values of 75.4% AP and 84.9% PolySim were achieved on the WHU dataset, effectively solving the problems of redundant vertices and contour smoothing, and providing high-precision building vector data support for scenarios such as smart cities and emergency response. Full article

We present a miniaturized, inexpensive, and user-friendly microfluidic platform to support biological applications. The system integrates a mini-incubator providing controlled environmental conditions and housing a microfluidic device for long-term cell culture experiments. The incubator is designed to be compatible with standard inverted optical microscopes and Raman spectrometers, allowing for the non-invasive imaging and spectroscopic analysis of cell cultures in vitro. The microfluidic device, which reproduces a dynamic environment, was optimized to sustain a passive, gravity-driven flow of medium, eliminating the need for an external pumping system and reducing mechanical stress on the cells. The platform was tested using Raman analysis and adherent tumoral cells to assess proliferation prior and subsequent to hydrogen peroxide treatment for oxidative stress induction. The results demonstrated a successful adhesion of cells onto the substrate and their proliferation. Furthermore, the platform is suitable for carrying out optical monitoring of cultures and Raman analysis. In fact, it was possible to discriminate spectra deriving from control and hydrogen peroxide-treated cells in terms of DNA backbone and cellular membrane modification effects provoked by reactive oxygen species (ROS) activity. The 800–1100 cm⁻¹ band highlights the destructive effects of ROS on the DNA backbone’s structure, as its rupture modifies its vibration; moreover, unpaired nucleotides are increased in treated sample, as shown in the 1154–1185 cm⁻¹ band. Protein synthesis deterioration, led by DNA structure damage, is highlighted in the 1257–1341 cm⁻¹, 1440–1450 cm⁻¹, and 1640–1670 cm⁻¹ bands. Furthermore, membrane damage is emphasized in changes in the 1270, 1301, and 1738 cm⁻¹ frequencies, as phospholipid synthesis is accelerated in an attempt to compensate for the membrane damage brought about by the ROS attack. This study highlights the potential use of this platform as an alternative to conventional culturing and analysis procedures, considering that cell culturing, optical imaging, and Raman spectroscopy can be performed simultaneously on living cells with minimal cellular stress and without the need for labeling or fixation. Full article

Reactive oxygen species (ROS) contribute to cerebral damage in transient cerebral ischemia, making their elimination a key therapeutic target. Osteogenic disorder Shionogi (ODS) rats, which lack endogenous L-ascorbic acid (AA) synthesis, serve as a useful model for investigating AA’s protective effects against ischemic brain injury. ODS rats were given an AA-free diet (0% AA), 0.1% AA, or 1% AA in drinking water for two weeks before undergoing middle cerebral artery occlusion and reperfusion (MCAO/Re). The 0% AA group exhibited pronounced damage following MCAO/Re, characterized by the induction of lipid peroxidation, O₂⁻ production, inflammation-related gene expression, and extensive infarct formation. In contrast, the 1% AA group showed reductions in these markers, along with fewer TUNEL-positive cells and a smaller infarct volume. Notably, sodium-dependent vitamin C transporter 2 (SVCT2) expression increased in both two AA-supplemented groups, although the 0.1% AA group did not exhibit sufficient improvement in post-ischemic damage. A two-week intake of AA significantly alleviated MCAO/Re-mediated injuries associated with oxidative stress and inflammation in ODS rats. Sufficient AA intake is thus supposed to mitigate ischemic damage, possibly through SVCT2 upregulation and enhanced AA availability, leading to the suppression of oxidative stress and inflammation. Full article

Regulating the innate immune response against infections, particularly drug-resistant bacteria, is a key focus in anti-infection therapy. Cathelicidins, found in vertebrates, are crucial for pathogen resistance. Few studies have explored gecko cathelicidins’ anti-infection properties. Recently, five new cathelicidins (Gj-CATH1-5) were identified in Gekko japonicus. The peptide Gj-CATH5, from G. japonicus, shows promise against Pseudomonas aeruginosa through various mechanisms. This study examined Gj-CATH5’s protective effects using in vitro and in vivo models, finding that it significantly reduced bacterial load in a mouse infection model when administered before or shortly after infection. Flow cytometry and the plate counting method showed that Gj-CATH5 boosts neutrophil and macrophage activity, enhancing chemotaxis, phagocytosis, and bactericidal functions. Gj-CATH5 increases ROS production, MPO activity, and NET formation, aiding pathogen clearance. Its amphipathic α-helical structure supports broad-spectrum bactericidal activity (MBC: 4–8 μg/mL) against Gram-negative and antibiotic-resistant bacteria. Gj-CATH5 is minimally cytotoxic (<8% hemolysis at 200 μg/mL) and preserves cell viability at therapeutic levels. These results highlight Gj-CATH5’s dual role in pathogen elimination and immune modulation, offering a promising approach to combat multidrug-resistant infections while reducing inflammation. This study enhances the understanding of reptilian cathelicidins and lays the groundwork for peptide-based immune therapies against difficult bacterial infections. Full article

Focused on the contradiction between the steady-state error of active power and the dynamic oscillation caused by the virtual damping characteristics of the virtual synchronous generator (VSG) under disturbances during grid-connected operation, this article proposes an adaptive virtual inertia regulation and compensation method (PFFCVSG_AJ) based on an active power differential feedforward compensation strategy (PFFCVSG). Firstly, this article presents the working and control principles of VSG, analyzing its control mechanisms through a small-signal model. Models for VSG’s active power, reactive power, and virtual impedance components are established, with particular focus on the impact of the damping coefficient on active power regulation. Based on the PFFCVSG, an adaptive virtual inertia adjustment method is introduced to resolve the inherent inertia deficiency in PFFCVSG control, the influence of the moment of inertia on PFFCVSG is theoretically analyzed, and a dynamic adjustment mechanism for moment of inertia is developed based on the rate of change in frequency (RoCoF). Finally, simulation validation using MATLAB/Simulink (MathWorks, R2022b, Natick, MA, USA) demonstrates that the proposed PFFCVSG_AJ strategy effectively eliminates active power steady-state deviation, suppresses active power dynamic oscillation, and mitigates the frequency overshoot issue prevalent in traditional PFFCVSG. Experimental verification is conducted via a TMS320F28378DPTPS-based control platform, confirming the algorithm’s effectiveness under sudden load variations, and that the power quality of the power grid is not affected under the premise of efficient grid connection. Full article

With the increasing popularity of low-cost, clean, and environmentally friendly new energy sources, the proportion of grid-connected new energy units has increased significantly. However, since these units are frequency decoupled from the grid through a power electronic interface, they are unable to provide inertia support during active power perturbations, which leads to a decrease in system inertia and reduced frequency stability. In this study, the urgent need to accurately assess inertia is addressed by developing an energy-function-based inertia identification technique that eliminates the effect of damping terms. By integrating vibration mechanics, the proposed method calculates the inertia value after a perturbation using port measurements (active power, voltage phase, and frequency). Simulation results of the Western System Coordinating Council (WSCC) 9-bus system show that the inertia estimation error of the method is less than 1%, which is superior to conventional methods such as rate-of-change-of-frequency (RoCoF) and least squares methods. Notably, the technique accurately evaluates the inertia of synchronous generators and doubly fed induction generators (DFIGs) under virtual inertia control, providing a robust inertia evaluation framework for low-inertia power systems with high renewable energy penetration. This research deepens the understanding of inertial dynamics and contributes to practical applications in grid stability analysis and control strategy optimalization. Full article

Oxidative stress is key in immune defense against fungal infections, such as those caused by Sporothrix schenckii, the dimorphic fungus responsible for sporotrichosis. Phagocytic cells utilize oxidative stress as a crucial mechanism to control pathogen spread. During S. schenckii infection, phagocytic cells recognize pathogen-associated molecular patterns (PAMPs) on their surface through conserved transmembrane or soluble receptors, known as pattern recognition receptors (PRRs). This recognition triggers a cascade of immune responses, including the generation reactive oxygen species (ROS) essential for pathogen elimination. However, S. schenckii has developed sophisticated mechanisms to evade and counteract this response, contributing to its persistence in the host. These mechanisms include the production of antioxidant enzymes, alterations to its cell wall (CW), and the production of melanin, which helps neutralize oxidative stress. In addition, S. schenckii modulates the production of other proteins, such as moonlighting proteins, suggested to have roles in immune evasion and stress response, helping its survival in the host. These strategies, along with the modulation of gene expression, allow the fungus to survive and persist inside the immune system’s hostile environment, facilitating the progression of the infection. Understanding these interactions between phagocytic cells and S. schenckii is key to developing more effective therapeutic strategies to combat sporotrichosis. Full article

Background and Objectives: Extracellular vesicles (EVs) derived from mesenchymal stem cells have gained much attention as potential therapeutic agents in many diseases, including hearing disorders such as sensorineural hearing loss (SNHL). EVs inherit similar therapeutic effects, including the stimulation of tissue regeneration from the parental cells. The aim of our study was to isolate EVs produced by MSCs and use them to treat inner ear cells in culture to evaluate their protective potential against the damaging effect of an ototoxic drug. Materials and Methods: We isolated MSC-derived EVs by precipitation and characterized them by number, size, and morphology using nanoparticle tracking analysis and TEM, evaluated the protein concentration by BCA assay and the presence of EV markers CD9, CD63, and CD81 by the Dot Blot immunoblotting method. HEI-OC1 inner ear cell line was treated with EVs either alone or followed by Cisplatin. We assessed the uptake of EVs in HEI-OC1 cells by fluorescence microscopy after PKH26 labeling, ROS production by the DCFDA (dichlorfluorescein diacetate) assay, cellular viability by Alamar Blue assay, and apoptosis with the Annexin V/Propidium Iodide method. Results: The isolated EVs had mean dimensions of 184.4 nms and the concentration of the EV suspension was 180 × 10⁶ particles/mL. TEM analysis showed intact vesicular structures with lipid-bilayer membranes having similar sizes with those measured by NTA. The PKH26-labeled EVs were observed in the HEI-OC1 cells after 24 h incubation, the amount increasing with the concentration. EVs reduced ROS production and increased the number of viable cells both alone and as pretreatment before Cisplatin, dose-dependently. Cells in early apoptosis were inhibited by EVs, while those in late apoptosis were enhanced, both with and without Cisplatin. Conclusions: EVs secreted by MSC protected HEI-OC1 cells against Cisplatin toxicity, reduced ROS production, and stimulated cell viability and the elimination of damaged cells by apoptosis, protecting the HEI-OC1 cells against Cisplatin-induced damage. Full article

Root-knot nematodes (RKNs), specifically Meloidogyne incognita, are notoriously difficult to eliminate as endophytic nematodes, and cause severe damage to various plants. Cucumber (Cucumis sativus), which is a cash crop widely grown across the world, is often infected by RKNs. ELONGATED HYPOCOTYL5 (HY5), a member of the bZIP transcription factor family, plays a vital role in hormone, nutrient, abiotic stress, biotic stress, and oxygen species (ROS) signaling pathways. However, the involvement of HY5 in the defense against RKNs has rarely been reported. The present study initially explored the response of CsHY5 to RKNs. The results indicated that the hy5 mutant had a higher number of nematodes and galls in the root system and exhibited a higher susceptibility to RKNs compared with the wild type (WT). Particularly, the root-knot nematodes in hy5 plants completed their life cycle more quickly and produced more eggs. The activities of defense-related hormones and antioxidant enzymes were measured, and the results indicated that JA, jasmonoyl-isoleucine (JA-Ile), abscisic acid (ABA), peroxidase (POD), and ascorbate peroxidase (APX) were significantly elevated in the wild type, but were not induced or decreased in the mutant. Through transcriptome sequencing analysis and quantitative real-time PCR (qRT-PCR), it was found that when RKNs infect plants, the key genes of jasmonic acid (JA) synthesis, CsAOC and CsAOS, as well as the key gene of the antioxidant system, CsPOD, were all significantly induced. Nevertheless, this induction effect disappeared in the hy5 mutant. Generally, CsHY5 plays a role in the response of cucumber to RKNs, and its deletion increases the sensitivity of cucumber to RKNs. These results suggest that CsHY5 may affect the resistance of cucumber to RKNs by affecting antioxidant enzyme activities and hormone content. Full article

Background/Objectives: Highly pathogenic coronaviruses (CoVs), including SARS-CoV, MERS-CoV, and SARS-CoV-2, continue to pose a significant threat to global public health. Therefore, this situation highlights the urgent need for effective broad-spectrum antiviral agents. Curcumin, a naturally occurring polyphenol known for its antiviral and anti-inflammatory properties, faces limitations such as poor bioavailability and rapid metabolic degradation, restricting its practical therapeutic application. Methods: To address these limitations, this study introduces a novel design strategy aimed at 42 new curcumin derivatives with improved pharmacokinetic profiles, specifically targeting the conserved coronavirus enzyme papain-like protease (PLpro). A comprehensive in silico evaluation was performed, including ADMET (Absorption, Distribution, Metabolism, Elimination, and Toxicity) analysis, molecular docking, molecular dynamics (MD) simulations, and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) calculations. Results: Extensive pharmacokinetic and toxicological assessments (ADMET analyses) identified 19 derivatives exhibiting optimal drug-like characteristics according to Lipinski’s Rule of Five (Ro5). Molecular docking analyses demonstrated that these novel derivatives possess significantly enhanced binding affinities to PLpro enzymes from SARS-CoV, MERS-CoV, and SARS-CoV-2 compared to standard antiviral agents and natural curcumin. Further validation through MD simulations and MM/PBSA calculations confirmed the structural stability and robust interactions of the most promising derivatives within the SARS-CoV PLpro active site. Conclusions: The results of this study provide essential structural and functional insights, reinforcing the potential of these newly developed curcumin derivatives as potent, broad-spectrum antiviral agents effective against current and future coronavirus threats. Full article

Recently, aquatic life and human health are seriously threatened by the release of pharmaceutical drugs. For a sustainable ecosystem, emerging contaminants like antibiotics must be removed from drinking water and wastewater. To address this issue pure and cerium-doped titanium dioxide (CeT) nanoparticles were produced with stable tetragonal (anatase) lattices by room temperature sol–gel method and employing the inorganic titanium oxysulfate (TiOSO₄) as titanium precursor. The structural analysis by X-ray diffraction (XRD) revealed that at calcination temperature of 600 °C all (un and doped) powders were composed of crystalline anatase TiO₂ with the crystallite sizes in the range of 13.5–11.3 nm. UV–vis DRS spectroscopy revealed that the most narrowed bandgap value of 2.75 eV was calculated for the 0.5CeT sample containing the optimum dopant content of 0.5 weight ratio. X-ray spectroscopy (XPS) confirmed the presence of the impurity level Ce³⁺/Ce⁴⁺, which became responsible for the decrease in bandgap as well as for the photoinduced carriers recombination rate. Photocatalytic tests showed that the maximum decomposition of the model spiramycin (SPR) antibiotic pollutant was 88.0% and 77.0%, under UV and visible light, respectively. According to the reaction kinetics, SPR decomposition adhered to the Langmuir–Hinshelwood (L–H) model and via ROS experiments mainly hydroxyl radicals (OH^•) followed by photogenerated holes (h⁺s) become responsible for the pollutant degradation. In summary, this study elaborates on the role of xCeT nanoparticles as an efficient photocatalyst for the elimination of organic contaminants in wastewater. Full article

For mobile agent path planning, traditional path planning algorithms frequently induce abrupt variations in path curvature and steering angles, increasing the risk of lateral tire slippage and undermining operational safety. Concurrently, conventional reinforcement learning methods struggle to converge rapidly, leading to an insufficient efficiency in planning to meet the demand for energy economy. This study proposes LSTM Bézier–Double Deep Q-Network (LB-DDQN), an advanced path-planning framework for mobile agents based on deep reinforcement learning. The architecture first enables mapless navigation through a DDQN foundation, subsequently integrates long short-term memory (LSTM) networks for the fusion of environmental features and preservation of training information, and ultimately enhances the path’s quality through redundant node elimination via an obstacle–path relationship analysis, combined with Bézier curve-based trajectory smoothing. A sensor-driven three-dimensional simulation environment featuring static obstacles was constructed using the ROS and Gazebo platforms, where LiDAR-equipped mobile agent models were trained for real-time environmental perception and strategy optimization prior to deployment on experimental vehicles. The simulation and physical implementation results reveal that LB-DDQN achieves effective collision avoidance, while demonstrating marked enhancements in critical metrics: the path’s smoothness, energy efficiency, and motion stability exhibit average improvements exceeding 50%. The framework further maintains superior safety standards and operational efficiency across diverse scenarios. Full article

Cold atmospheric plasma (CAP) acts as a powerful antibacterial tool in the food industry, effectively eliminating E. coli and a wide range of pathogens, including bacteria, viruses, fungi, spores, and biofilms in meat and vegetables. Unlike traditional bactericidal methods, CAP leverages an arsenal of reactive species, including reactive oxygen species (ROS) such as ozone (O3) and hydroxyl radicals (OH•), and reactive nitrogen species (RNS) like nitric oxide (NO•), alongside UV radiation and charged particles. These agents synergistically dismantle E. coli’s cell membranes, proteins, and DNA, achieving high degradation rates without thermal or chemical damage to processed food. This non-thermal, eco-friendly technology preserves food’s nutritional and sensory integrity, offering a transformative edge over conventional approaches. It emphasizes the critical need to optimize treatment parameters (exposure time, gas composition, power) to unlock CAP’s full potential. This review explores CAP’s effectiveness in degrading E. coli, emphasizing the optimization of treatment parameters for practical food industry applications and its potential as a scalable food safety solution. It is crucial to conduct further studies to enhance its implementation, establishing CAP as a fundamental element of advanced food processing technologies and a key measure for protecting public health. Full article

Inflammation is a multifaceted biological response of the immune system against various harmful stimuli, including pathogens (such as bacteria and viruses), cellular damage, toxins, and natural/synthetic irritants. This protective mechanism is essential for eliminating the cause of injury, removing damaged cells, and initiating the repair process. While inflammation is a fundamental component of the body’s defense and healing process, its dysregulation can lead to pathological consequences, contributing to various acute and chronic diseases, such as autoimmune disorders, cancer, metabolic syndromes, cardiovascular diseases, neurodegenerative conditions, and other systemic complications. Generally, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), antihistamines, biologics, and colchicine are used as pharmacological agents in the management of inflammatory diseases. However, these conventional treatments often have limitations, including adverse side effects, long-term toxicity, and drug resistance. In contrast, enzyme-based therapeutics have emerged as a promising alternative due to their high specificity, catalytic efficiency, and ability to modulate inflammatory pathways with reduced side effects. These enzymes function by scavenging reactive oxygen species (ROS), inhibiting cytokine transcription, degrading circulating cytokines, and blocking cytokine release by targeting exocytosis-related receptors. Additionally, their role in tissue repair and regeneration further enhances their therapeutic potential. Most natural anti-inflammatory enzymes belong to the oxidoreductase class, including catalase and superoxide dismutase, as well as hydrolases such as trypsin, chymotrypsin, nattokinase, bromelain, papain, serratiopeptidase, collagenase, hyaluronidase, and lysozyme. Engineered enzymes, such as Tobacco Etch Virus (TEV) protease and botulinum neurotoxin type A (BoNT/A), have also demonstrated significant potential in targeted anti-inflammatory therapies. Recent advancements in enzyme engineering, nanotechnology-based enzyme delivery, and biopharmaceutical formulations have further expanded their applicability in treating inflammatory diseases. This review provides a comprehensive overview of both natural and engineered enzymes, along with their formulations, used as anti-inflammatory therapeutics. It highlights improvements in stability, efficacy, and specificity, as well as minimized immunogenicity, while discussing their mechanisms of action and clinical applications and potential future developments in enzyme-based biomedical therapeutics. Full article