Search Results (22,435)

Multiple Unmanned Aerial Vehicle (UAV) collaborative coverage path planning is widely applied in fields such as regional surveillance. However, optimizing the trade-off between deployment costs and task execution efficiency remains challenging. To balance resource costs and execution efficiency with an uncertain number of UAVs, this paper analyzes the characteristics of irregular mission areas and formulates a bi-level optimization model for multi-UAV collaborative CPP. The model aims to minimize both the number of UAVs and the total path length. First, in the upper level, an improved Best Fit Decreasing algorithm based on binary search is designed. Straight-line scanning paths are generated by determining the minimum span direction of the irregular regions. Task allocation follows a longest-path-first, minimum-residual-range rule to rapidly determine the minimum number of UAVs required for complete coverage. Considering UAV’s turning radius constraints, Dubins curves are employed to plan transition paths between scanning regions, ensuring path feasibility. Second, the lower level transforms the problem into a Multiple Traveling Salesman Problem that considers path continuity, range constraints, and non-overlapping path allocation. This problem is solved using an Improved Biased Random Key Genetic Algorithm. The algorithm employs a variable-length master–slave chromosome encoding structure to adapt to the task allocation of each UAV. By integrating biased crossover operators with 2-opt interval mutation operators, the algorithm accelerates convergence and improves solution quality. Finally, comparative experiments on mission regions of varying scales demonstrate that, compared with single-level optimization and other intelligent algorithms, the proposed method reduces the required number of UAVs and shortens the total path length, while ensuring complete coverage of irregular regions. This method provides an efficient and practical solution for multi-UAV collaborative CPP in complex environments. Full article

Power supply for traction substations (TSs) of AC railways has traditionally been provided by 110–220 kV overhead transmission lines (OHL). These OHLs can be damaged during strong winds and ice formation. Furthermore, these lines generate significant electromagnetic fields (EMFs), which adversely affect maintenance personnel, the public, and the environment. Mitigating the resulting damages requires the establishment of protection zones, necessitating significant land allocation. Enhancing the reliability of power supply to traction substations and reducing EMF levels can be achieved through the use of gas-insulated lines (GIL), whose application in the power industry of many countries is continuously increasing. The aim of the research presented in this article was to develop computer models for determining the EMF of a GIL supplying a group of traction substations, taking into account actual traction loads characterized by non-sinusoidal waveforms and asymmetry. To solve this problem, an approach implemented in the Fazonord AC-DC software package, based on the use of phase coordinates, was applied. This allowed for the correct accounting of the skin effect and proximity effect in the massive current-carrying parts of the GIL, as well as the influence of asymmetry and harmonic distortions. The simulation results showed that the use of GIL brings the voltage unbalance factors at the 110 kV busbars of the traction substations within the permissible range, with the maximum values of these coefficients not exceeding 2%. The results of the harmonic distortion assessment demonstrated a significant reduction in harmonic distortion factors in the 110 kV network for the GIL compared to the OHL. The performed electromagnetic field calculations confirmed that the GIL generates magnetic field strengths one order of magnitude lower than those of the OHL. The obtained results lead to the conclusion that the use of gas-insulated lines for powering traction substations is highly effective, ensuring increased reliability, improved power quality, and a reduced negative impact of EMF on personnel, the public, the environment, and electronic equipment. Full article

As distribution networks become increasingly intelligent, primary–secondary integrated distribution switches are replacing the traditional electromagnetic type. However, the high degree of integration intensifies inherent electromagnetic compatibility (EMC) challenges. This paper presents a field-circuit hybrid full-wave model to investigate switch characteristics during lightning strikes. A 3D full-wave model of the switch and a distributed parameter circuit model of the connecting lines are coupled via a network parameter matrix. This approach comprehensively accounts for the impacts of transmission lines and structural components on electromagnetic disturbances. Simulation and experimental results reveal that lightning strikes induce high-frequency damped oscillatory waves, primarily caused by traveling wave reflections along overhead lines. The characteristic frequency of disturbance is inversely proportional to the transmission line length. Additionally, internal components significantly influence this frequency; specifically, a larger voltage dividing capacitance in the voltage transformer results in a lower frequency. Model validation was performed using a 20 m transmission line setup. A 75 kV standard lightning impulse was injected into Phase B. At a distance of 500 mm from the voltage transformer, the measured radiated electric field amplitude was 14.12 kV/m (deviation < 5%), and the characteristic frequency was 1.11 MHz (deviation < 20%). These findings offer vital guidance for the lightning protection and EMC design of primary–secondary integrated distribution switches. Full article

Owing to their high strength characteristics, chemical stability, and piezoelectric activity, vinylidene fluoride (VDF) copolymers have become promising materials for creating implants to replace bone tissue defects. However, a significant drawback of these materials is the biological inertness of their surface, which leads to unsatisfactory integration with the patient’s bone tissue. In this study, we propose a single-step approach for immobilizing hydroxyapatite (HAp) on the surface of porous implants made of vinylidene fluoride and tetrafluoroethylene copolymer (P(VDF-TeFE)). This method consists of treating the surface of the product with a mixture of solvents while simultaneously capturing HAp microparticles. Using scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS), it was shown that the proposed method preserves the morphology of model implants (pore diameter and printed line thickness) and allows HAp to cover up to 63 ± 14% of their surface, reaching concentrations of calcium and phosphorus up to 6.0 ± 1.3 and 3.6 ± 0.7 at. %, respectively, imparting superhydrophilic properties to them. Optical profilometry revealed that the surface roughness of samples increased by more than seven times as a result of HAp immobilization. X-ray diffraction analysis (XRD) confirmed that the piezoelectric phase of P(VDF-TeFE) is preserved after treatment, as are the compressive strength characteristics of the samples. Hydroxyapatite immobilization significantly improved the adhesion and osteogenic differentiation of multipotent stem cells cultured with P(VDF-TeFE)-based samples. Thus, the proposed method can significantly enhance the biological activity of implants based on the piezoelectric VDF copolymer. Full article

Background: Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota’s role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro β-carboline carboxylic acid (THC), in targeting some hallmark traits of PC and CRC, both as standalone agents and in combination with standard chemotherapeutics (gemcitabine for PC and 5-fluorouracil (5-FU) for CRC). Methods: Cell viability assays and IC₅₀ determination was assessed using either the Muse™ Count & Viability Kit or the Sulforhodamine B assay; cell death was determined by Annexin V/Propidium Iodide and cell cycle assessed by Propidium Iodide was analyzed by flow cytometry. Results: Here, we found that NAC selectively reduced the viability of PC cells BxPC-3 without triggering apoptosis, while effectively inducing apoptosis in PC cells Panc-1 and in CRC cell lines. THC exhibited stronger anticancer activity, inhibiting proliferation and promoting apoptosis in all tested PC and CRC cells, even at lower concentrations. Combination treatments yielded promising enhancement effects. NAC enhanced the cytotoxicity of gemcitabine in Panc-1 cells through increased apoptosis. NAC, when combined with 5-FU, also increased apoptosis of CRC cells. THC further potentiated gemcitabine’s impact on Panc-1 cells by increasing apoptosis and by inducing cell cycle changes in BxPC-3. In the CRC model, THC co-treatment with 5-FU reduced cell viability and increased apoptosis in all cells. Conclusions: These findings provide preliminary in vitro evidence supporting the potential of integrating microbiota-derived postbiotics with conventional chemotherapy both in PC and CRC. Full article

Taraxacum kok-saghyz (Tks) is a promising plant species for natural rubber (NR) production and represents a model for studying NR biosynthesis in the Asteraceae family. The generation of transgenic plants overexpressing a gene of interest is a well-established strategy to investigate gene function and potential interactions. Here, we present a comprehensive workflow—from the construction of an overexpression vector to the generation, identification, and propagation of stable transgenic Tks lines. In addition, we describe a rapid and reliable method for quantifying NR content in transformed plants, providing essential phenotypic characterisation in this species. Full article

Background/Objectives: Breast cancer cells rely on both mitochondrial metabolism and proteostatic mechanisms for cell fitness. The mitochondrial enzyme IDH2 supports redox balance and biosynthesis, while the ubiquitin-proteasome system (UPS) preserves protein quality. This study aimed to determine whether inhibiting IDH2 enhances sensitivity to proteasome-targeting agents across breast cancer subtypes. Methods: A panel of human and murine breast cancer cell lines was treated with the IDH2 inhibitor AGI-6780, alone or in combination with the proteasome inhibitor carfilzomib (CFZ) or the E1 ubiquitin-activating enzyme inhibitor TAK-243. Synergy was evaluated using Bliss scoring. Apoptosis, clonogenicity, and pathway modulation were assessed through Western blotting, colony-formation assays, and reverse-phase protein array (RPPA) profiling. Results: We observed that co-targeting IDH2 and the UPS produced strong synergistic cytotoxicity in multiple breast cancer models, including in triple-negative MDA-MB-231 and 4T1 cells (Bliss > 25). Combination treatments led to pronounced apoptosis, evidenced by cleaved PARP-1 and Caspase-3 cleavage, and a marked loss of clonogenic potential. RPPA analysis revealed significant alterations in key survival and stress-response pathways, including NF-κB, PI3K-p85, Src, and p38-MAPK. Conclusions: Inhibition of IDH2 markedly enhances the cytotoxic effects of proteasome-targeting by disrupting metabolic–proteostatic balance and promoting apoptotic cell death. These findings identify a growth-inhibitory effect that may be leveraged to improve functional dependency in breast cancer, particularly in triple-negative breast cancer, which currently lacks efficient drug treatments. Full article

Background/Objectives: Nutraceuticals, including short-chain fatty acids (SCFAs) and antioxidants (AOXs), are nutrient-derived bioactive compounds considered as potential treatments for metabolic-associated steatotic liver disease (MASLD). However, in vitro studies of their effects are limited by inconsistent experimental conditions, including differences in cell lines, methods of steatosis induction, and culture media, and by reliance on qualitative rather than quantitative assessments. Here, we systematically evaluate the anti-steatotic potential of eight commonly used nutraceuticals—three SCFAs (butyrate, acetate, and propionate) and five AOXs (resveratrol, curcumin, berberine, chlorogenic acid, and vitamin E)—using a standardized in vitro approach. Methods: Following a systematic literature review to identify common experimental conditions, we developed an assay to validate steatosis induction and quantified the effects of the nutraceuticals. For our studies we used the HepG2 liver cancer cell line and the Fa2N-4 immortalized hepatocyte cell line. Steatosis was modeled by stimulating cells with free fatty acids and fructose for 48 h. Nutraceuticals were added either concurrently with steatotic stimulation, to assess preventive effects, or after 24 h to assess therapeutic effects. Anti-steatotic drugs (resmetirom, semaglutide, obeticholic acid, and a DGAT2 inhibitor) were included as positive controls. Intracellular triglyceride levels were measured to quantify steatosis. Results: A systematic review of 46 studies revealed large differences in culture conditions, steatosis induction, and nutraceutical assessment. In our experiments, most nutraceuticals did not reduce intracellular triglycerides, with the exception of vitamin E. Surprisingly, butyrate, berberine, and curcumin increased triglyceride accumulation. Resmetirom was the only drug that significantly decreased triglycerides, while obeticholic acid, semaglutide, and the DGAT2 inhibitor showed minimal or inconsistent effects. Fa2N-4 cells were generally more sensitive than HepG2 cells, showing larger absolute changes in triglyceride levels in response to both nutraceuticals and resmetirom. Conclusions: We established a standardized in vitro assay to evaluate the anti-steatotic potential of nutraceuticals. Using this system, we found that SCFAs and AOXs did not consistently reduce intracellular triglycerides, highlighting the need for quantitative assessments and careful validation when studying anti-steatotic interventions in vitro. Full article

Background: Triple-negative breast cancers (TNBCs) are among the most aggressive breast tumors, due not only to the absence of clinically functional biomarkers used in other molecular subtypes, but also their marked heterogeneity and pronounced migratory and invasive behavior. The search for new molecules of interest for risk prediction, diagnosis and therapy stems from the class of long non-coding RNAs (lncRNAs), which often display context-dependent (“dual”) functions and tissue specificity. Among them, lncRNA LINC01133 stands out for its dysregulation across cancer, although its molecular role in TNBC remains unclear. Methods: In the present study, we used the human TNBC cell line Hs578T to generate a cell panel comprising the parental line (Hs578T_wt), the control line (Hs578T_ctr), and the LINC01133 knockout line (Hs578T_ko). Subsequently, we performed bulk RNA-Seq to identify KO-associated Differentially Expressed Genes (DEGs) using ko_vs_ctr as the primary contrast. Functional interpretation was achieved by Over-Representation Analysis (ORA) using Gene Ontology. We then conducted a comparative patient-cohort analysis using TCGA-BRCA Basal-like/TNBC cases (TCGA/BRCA n = 1098; Basal-like/TNBC n = 199), classified with the AIMS algorithm, and evaluated concordance between KO-associated signatures and patient tumor expression patterns via trend-based analyses across the LINC01133 expression levels and associated genes. Results: A total of 265 KO-dominant DEGs were identified in Hs578T_ko, reflecting transcriptional changes consistent with tumor progression, with enrichment of pathways associated with LINC01133 knockout including cell adhesion, cell–cell interactions, epithelial–mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. The main DEGs included ITIH5, GLUL, CACNB2, PDX1, ASPN, PTGER3, MFAP4, PI15, EPHB6, and CPA3 with additional candidates, such as KAZN and the lncRNA gene SSC4D, which have been implicated in migration/invasion, ECM remodeling, or signaling across multiple tumor contexts. Translational analyses in TCGA-BRCA basal-like tumors suggested a descriptive association in which lower LINC01133 levels were accompanied by shifts in the expression trends of genes linked to ECM/EMT programs and modulation of genes related to cell adhesion and protease inhibition. Conclusions: These results suggest a transcriptional model in which LINC01133 is associated with TNBC-related gene expression programs in a concentration-dependent manner, with loss of LINC01133 being associated with a transcriptomic shift toward pro-migratory/ECM remodeling signatures. While functional validation is required to establish causality, these data support LINC01133 as a molecule of interest in breast cancer research. Full article

Background/Objectives: Breast cancer is the most frequently diagnosed malignancy among women and is characterized by marked heterogeneity in treatment response. Metabolic reprogramming, particularly enhanced de novo lipogenesis, represents a hallmark of cancer progression and a promising therapeutic target. Firsocostat, a selective allosteric inhibitor of acetyl-CoA carboxylase (ACC), has previously been investigated in metabolic diseases but has never been evaluated in breast cancer models. This study aimed to assess the antitumor effects of firsocostat on breast cancer cell lines. Methods: We investigated the cytotoxic and metabolic effects of firsocostat in four breast cancer cell lines—MCF7 (luminal A HR⁺), SK-BR-3 (HER2-positive), MDA-MB-231 (triple-negative), and HCC1937 (triple-negative, BRCA1-mutated)—together with the non-tumorigenic MCF-10A line. Dose- and time-dependent responses were evaluated using phase-contrast microscopy for morphological evaluation, Trypan Blue exclusion assays, and MTS-based viability assays. Results: Firsocostat significantly reduced cell viability across all breast cancer subtypes in a concentration- and time-dependent manner, with IC₅₀ values ranging from 80 to 93 µM. In contrast, non-tumorigenic MCF-10A cells were less affected, indicating a selective cytotoxic effect toward malignant cells. Conclusions: Firsocostat exerts robust cytotoxic effects in breast cancer models, identifying it as a promising metabolism-targeting therapeutic candidate capable of selectively impairing breast cancer cell survival by disrupting fatty acid biosynthesis. These results indicate that firsocostat could represent a viable candidate as a metabolic-based therapeutic approach for breast cancer. Given its established clinical safety profile in metabolic diseases, firsocostat warrants further preclinical investigation and supports further mechanistic and preclinical evaluation. Full article

Background/Objectives: Triple negative breast cancer (TNBC) is an aggressive subtype treated primarily with chemotherapy, which often leads to drug resistance (DR) and reduced effectiveness. Phytochemicals, including anthocyanins from dark sweet cherry (ACN), have emerged as potential adjuvants to overcome DR, though mechanisms remain unclear. This study examines ACN effects on canonical and non-canonical antioxidant pathways (Nrf2-Keap1 and p62) as a mechanism to overcome DR in 4T1 TNBC cells with acquired DR. Methods: Two conditions were tested: ACN with basal doxorubicin (DOX) as resistance-maintaining conditions and ACN with DOX at IC₅₀ to induce oxidative stress (OS). Results: Under resistance-maintaining conditions, ACNs activated the canonical Nrf2-Keap1 pathway at high doses, which can potentially contribute to DR development due to its cellular protection effects. However, at a low dose, ACN did not trigger an antioxidant response linked to GST and GGT enzyme activities and instead impaired autophagy, increasing OS. Under OS, ACN activated the non-canonical antioxidant pathway mediated by p62 while deactivating Nrf2, leading to autophagy-induced cell death and further impairing autophagy at a low dose. Notably, inflammation persisted at both treatment levels without being relieved, keeping stress signaling active. At both conditions, ACN at doses likely attainable under physiological conditions effectively impaired autophagy and elevated OS, resulting in cell death. Conclusions: These results underscore the context-dependent dual function of polyphenols in cancer therapy, demonstrating their potential to enhance cellular sensitivity to chemotherapy and providing guidance for their strategic use as adjuvants in treating TNBC and overcoming DR. However, this study was limited to a single cell line derived from a murine model. Future research should include comparative studies using human TNBC cell lines to validate these findings and better assess their translational relevance. Full article

Emerging landslides and severe floods highlight the urgent need to analyse and support predictive models and early warning systems. Soil moisture is a crucial parameter and it can now be determined from space with a resolution of a few tens of meters, potentially leading to the continuous global monitoring of landslide risk. We address this issue by determining the volumetric water content (VWC) of a testbed in Southern Italy (bare soil with significant flood and landslide hazard) through the comparison of two different satellite observations on the same day. In the first observation (Sentinel-1 mission of the European Space Agency, C-band Synthetic Aperture Radar (SAR)), the back-scattered radar signal is used to determine the VWC from the dielectric constant in the microwave range, using a time-series approach to calibrate the algorithm. In the second observation (hyperspectral PRISMA mission of the Italian Space Agency), the short-wave infrared (SWIR) reflectance spectra are used to calculate the VWC from the spectral weight of a vibrational absorption line of liquid water (wavelengths 1800–1950 nm). As the main result, we obtained a Pearson’s correlation coefficient of $0.4$ between the VWC values measured with the two techniques and a separate ground-truth confirmation of absolute VWC values in the range of 0.10–0.30 within $\pm 0.05$. This overlap validates that both SAR and hyperspectral data can be well calibrated and mapped with 30 m ground resolution, given the absence of artifacts or anomalies in this particular testbed (e.g., vegetation canopy or cloud presence). If hyperspectral data in the SWIR range become more broadly available in the future, our systematic procedure to synchronise these two technologies in both space and time can be further adapted to cross-validate the global high-resolution soil moisture dataset. Ultimately, multi-mission data integration could lead to quasi-real-time hydrogeological risk monitoring from space. Full article

Background: Ovarian granulosa cells (GCs) play a pivotal role in folliculogenesis, and their dysfunction is central to disorders such as polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). MicroRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of GC homeostasis. Method: This review synthesizes current evidence by systematically analyzing relevant studies, integrating data from in vitro GC models, animal experiments, human cell lines, and clinical samples to elucidate the specific mechanisms by which miRNAs regulate GCs. Results: miRNAs precisely modulate GC proliferation, apoptosis, steroidogenesis, and oxidative stress responses by targeting key signaling pathways (e.g., PI3K/AKT/mTOR, TGF-β/SMAD) and functional genes (e.g., TP53, CYP19A1). Exosomal miRNAs serve as vital mediators of communication within the follicular microenvironment. To date, nearly 200 miRNAs have been associated with PCOS. Conclusions: miRNAs constitute a decisive regulatory network governing GC fate, offering promising therapeutic targets for PCOS and POF. However, significant challenges remain, primarily miRNA pleiotropy and the lack of follicle-specific delivery systems. Future clinical translation requires rigorous validation in human-relevant models. Full article

White lupin (Lupinus albus) is a very important legume crop, having seeds with high protein content but also quantities of antinutritional alkaloids. Regarding cultivation, it is sensitive to neutral or alkaline soil conditions, although it is well adapted to drought conditions. In this study, the adaptability of 17 L. albus (14 commercial varieties and 3 advanced lines) genotypes to neutral-pH soils was investigated in relation to morphological, agronomical, and yield attributes. An extended characterization of seed composition for total alkaloids, trypsin inhibitors, phenolics, tannins, total nitrogen, NDF, ADF, and lignin was also performed. Furthermore, a prebreeding program consisting of 140 targeted crosses was initiated to develop new F1 combinations for genotypes with low alkaloid profiles; at the same time, controlled self-fertilization of elite lines was carried out. The results indicated that the morphological response of L. albus to neutral pH was positive and significantly genotypically dependent. Among the varieties tested, ‘Magnus’ and ‘Figaro’ showed low alkaloid and lignin contents. On the other hand, the advanced lines (LKAP, LKML, LKAU) had high antinutritional components, even though they were high-yielding. This research proposes a model of combined evaluation and selection processes for identification of particular genotypes that can perform well in neutral soils and provides the basis for breeding and producing low-alkaloid genotypes for multi-locational exploitation. Full article

Background/Objectives: Imatinib, the first tyrosine kinase inhibitor, marks the beginning of a revolution in clinical oncology. Disrupting oncogenic kinase-dependent signaling pathways represents a key strategy for advancing targeted cancer therapies. Terpene analogues of imatinib were developed to probe the influence of terminal ring modifications on BCR-ABL inhibition and downstream oncogenic signaling. Methods: Nine novel imatinib analogues bearing bulky aliphatic moieties were designed, synthesised, and structurally characterized by ¹H/¹³C NMR spectroscopy and high-resolution mass spectrometry (HRMS). Molecular docking calculations were performed to assess the binding modes and intermolecular interactions. The cytotoxicity of the newly synthesized imatinib derivatives was evaluated across a panel of BCR-ABL+ leukemia cell lines. Results: Molecular docking analyses demonstrated conserved interactions within the ATP-binding site of BCR-ABL for all derivatives, with calculated docking scores ranging between 123 and 128, while modifications at the terminal ring introduced subtle changes in electrostatic and steric profiles. Biological evaluation using MTT-based cytotoxicity assays in BCR-ABL+ leukemic cell lines revealed enhanced antiproliferative activity compared with imatinib, with compounds 6a (flexible cyclohexyl) and 6d (rigid camphane-type (+)-isopinocampheyl) exhibiting the lowest micromolar activity in the AR-230 model (IC₅₀ values of 1.1 and 1.2 μM, respectively). Proteome-wide phosphokinase profiling demonstrated shared suppression of STAT5/3/6, RSK1/2, S6K1/p70, and Pyk2, confirming effective disruption of canonical BCR-ABL pathways. Critically, the terpene moiety dictated downstream pathway bias: 6a preferentially attenuated CREB activation, whereas 6d more effectively suppressed the PI3K/Akt oncogenic axis and strongly activated proapoptotic p53-mediated stress responses. Conclusions: Our findings establish terpene-engineered imatinib analogues as tunable modulators and promising candidates for targeting downstream BCR-ABL signaling pathways in leukemia treatment. Full article