Search Results (6,654)

Calmodulin-like proteins (CMLs) serve as core components in plant calcium signal transduction pathways, and they extensively modulate plant growth, development, and adaptive responses to various abiotic stresses. In this study, we cloned the StCML19 gene from potato and generated stable transgenic Arabidopsis thaliana lines constitutively expressing this gene to investigate its functional role under drought stress. Transcriptome analysis revealed that StCML19 was up-regulated under drought conditions. Phenotypic assays showed that overexpressing StCML19 notably increased the seed germination rate and root length of transgenic Arabidopsis under mannitol-induced osmotic stress, and greatly improved the plant survival rate under severe soil drought stress. Physiological analysis showed that when put under drought stress, transgenic plants had higher proline content, better SOD, CAT, and POD activities, and significantly less malondialdehyde (MDA) accumulation than wild-type plants. In addition, overexpression of StCML19 led to greater plant sensitivity to exogenous ABA, with inhibited root growth and delayed seed germination as indicators. Conclusively, this study is the first to make sense of the biological function of potato StCML19 in the drought stress response and views StCML19 as a promising candidate gene for the genetic improvement of drought-tolerant potato varieties. Full article

Background: Sorafenib resistance remains a major barrier to effective therapy in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Introduction: Here, we identified a previously undefined mechanism by which miR-21 promotes sorafenib resistance by suppressing the tumor suppressor SASH1 and enhancing HBx-driven PI3K/AKT/mTOR signaling. Methods: miR-21 expression was markedly elevated in HBV-HCC tissues, HBV-integrated HCC cell lines, and hypoxic conditions. Bioinformatic analyses and luciferase reporter assays confirmed SASH1 as a direct miR-21 target. Results: Mechanistically, SASH1 was functionally associated with HBx-related oncogenic signaling and influenced apoptotic responses. miR-21 inhibition reduced HBV-HCC cell proliferation, increased apoptosis, and restored sorafenib sensitivity in vitro. In an orthotopic HBV-HCC mouse model, the combined administration of miR-21 inhibitor and sorafenib elicited markedly greater tumor suppression and restoration of the SASH1 expression than either monotherapy did. Discussion: Therefore, these findings suggested that the miR-21/SASH1 pathway contributed to therapeutic resistance in HBV-associated HCC and highlighted that miR-21 targeting could be an efficient strategy to improve sorafenib response. Conclusions: The miR-21/SASH1 axis play a critical role in sorafenib resistance in HBV-associated HCC, and targeting miR-21 may provide a promising therapeutic strategy to enhance treatment efficacy. Full article

Railway traffic monitoring requires robust detection technologies capable of operating reliably under real-world vibration and environmental conditions. In this work, we present the design and validation of an optical vibration sensor based on a Single-mode–Multimode–Single-mode (SMS) fiber structure for Light Rail Vehicle (LRV) detection. The sensing mechanism relies on multimodal interference in the multimode fiber (MMF), where rail-induced vibrations modify the guided mode distribution and, consequently, the transmitted optical intensity. The optical signal is converted to voltage and processed through an embedded acquisition system. Additionally, we conducted tests with freight trains and maintenance trains in order to evaluate the applicability of the sensor in other types of trains besides the LRV. We conducted laboratory experiments to assess mechanical stability, sensibility, and packaging strategies, followed by supervised field tests on an operational LRV line. The recorded time-domain signal exhibited clear modulation during train passage, and first-derivative and sliding-window variance analyses were applied to reliably identify vibration events, even in the presence of slow baseline drift. In addition, frequency-domain analysis was performed by applying the Fast Fourier Transform (FFT) to the measured signal, enabling the identification of characteristic low-frequency spectral components induced by train passage. A quantitative sensitivity assessment was further carried out by correlating the integrated spectral energy (0–12 Hz) with vehicle weight, yielding a linear response with a sensitivity of 0.0017 a.u./t and coefficient of determination $R^2=0.933$. The proposed solution demonstrated stable operation using commercially available low-cost components, confirming the feasibility of SMS-based optical sensing for railway monitoring. These results indicate strong potential for future deployment in traffic safety systems and distributed sensing networks. Full article

This paper considers a principle for constructing transverse differential protection of two parallel 6–35 kV power transmission lines on the supply side, previously proposed by the authors and protected by a patent. Its implementation makes it possible to identify the damaged line without using current and voltage transformers, by employing signals from reed switches installed near the corresponding phases of the lines. The principle is based on monitoring the difference in magnetic field inductions produced by the currents in these phases and determining the damaged line according to the sequence of reed switch actuations. Based on experimental studies of the temporal characteristics of reed switches and on simulation of magnetic fields around the line phases, methodologies for selecting protection operating parameters and for evaluating its sensitivity, taking into account the influence of errors and currents in the phases of both lines, have been developed; the field of application of the protection, the cascade zone, and the locations for installing the reed switches have been determined. It is shown that the calculated cascade zone of the proposed protection can be up to 20% shorter than that of both the traditional protection and a similar reed-switch-based protection. At the same time, in comparison with the latter, implementation of the considered principle requires three times fewer reed switches. The elimination of current and voltage transformers, as shown by the calculations, creates prerequisites for reducing the resource intensity of the protection. Full article

Endometriosis is associated with nociceptive pain, as well as peripheral and central sensitization. Evidence-based treatment suggestions for controlling endometriosis should be based on the convergence of the best scientific evidence, physicians’ clinical expertise, and the values and priorities of individual patients. In this non-systematic, comprehensive narrative review, data from available randomized controlled trials and meta-analyses on hormonal treatment for symptomatic endometriosis are interpreted through the lens of clinical experience. The role of patients in defining therapeutic trade-off balances is also taken into consideration. Most symptomatic patients benefit from hormonal therapy, including first-line (progestogens and estrogen-progestogen combinations) and second-line (GnRH agonists and antagonists) medications, to relieve nociceptive pain. To reduce the risk of venous and arterial thrombosis and avoid stimulating lesions, it is preferable to use combinations containing body-identical estrogens rather than ethinyl-estradiol. The main adverse effect of first-line medications is irregular bleeding, which adversely impacts efficacy, tolerability, and adherence. If progestogens and estrogen-progestogens do not improve health-related quality of life (HRQoL), promptly stepping up to GnRH analogues combined with add-back therapy is indicated. Add-on rather than upfront combination therapy is suggested. Separating the analogues and add-back therapy allows for choosing the compounds that best suit the characteristics of individual patients. Transdermal body-identical estradiol use is proposed in combination with both progestogens and GnRH analogues. Similar satisfactory outcomes are achieved with GnRH agonists and antagonists. Evidence on the use of neuromodulatory drugs to treat neuropathic and nociplastic pain is derived from studies of other chronic pain conditions and shows limited effectiveness. The two mainstays of hormonal therapy are (i) ovariostasis and (ii) amenorrhea. “Medical treatment failure” should not be declared unless a shift from first-line to second-line medications has been undertaken whenever these conditions are not met. For severely symptomatic adolescents and young women, secondary prevention through ovariostasis and amenorrhea should be pursued promptly to improve HRQoL, halt lesion progression, and preserve reproductive potential. Full article

Background: Fumonisin B1 (FB1) is a toxic secondary metabolite produced by Fusarium species that commonly contaminates cereal crops, posing serious threats to crop productivity and food safety. In plants, FB1 inhibits ceramide synthase, disrupts sphingolipid metabolism, and induces growth inhibition and programmed cell death. Despite the agricultural importance of fumonisin contamination, genetic strategies to enhance FB1 tolerance or detoxification capacity in crops remain limited, largely due to an incomplete understanding of the underlying genetic determinants. Methods: To identify genetic determinants associated with FB1 tolerance, we exploited natural variation in Arabidopsis thaliana and conducted a genome-wide association study (GWAS). Candidate genes were further examined using gene expression analyses and functional characterization of overexpression and SALK mutant lines. Results: GWAS revealed a significant association locus on chromosome 1 linked to FB1 tolerance. Two adjacent genes within this locus, AT1G14750 and AT1G14755, were identified as positive regulators of FB1 tolerance. Both genes were rapidly induced upon FB1 exposure. Functional analyses demonstrated that overexpression of either gene significantly enhanced tolerance to FB1-induced damage, whereas SALK mutant lines displayed increased sensitivity, manifested by enhanced growth inhibition and necrosis. Conclusions: Our study identifies AT1G14750 and AT1G14755 as previously uncharacterized components of FB1 tolerance in Arabidopsis. These findings provide new insights into the genetic architecture of plant response to mycotoxin stress and establish a foundation for further studies on the molecular mechanisms underlying FB1 tolerance. Full article

Wheeled multifunctional motorized crossing frames represent a new type of crossing equipment for high-voltage transmission line construction. The initial design is too conservative, having a large safety margin and high material redundancy. Therefore, it is necessary to study a lightweight design version. However, as the structure constitutes an assembly consisting of multiple components, it also exhibits relatively high complexity. In a lightweight design, optimizing multi-component and multi-size parameters can lead to structural interference and separation, seriously affecting the smooth progress of design optimization. Therefore, an optimization design method of a multi-parameter complex assembly structure is proposed to solve this problem. Firstly, the typical stress conditions of the wheeled multifunctional motorized crossing frame were analyzed using its structural model. Then, a finite element model of the beam was established in ANSYS 2021 R1 Workbench, and the mechanical characteristics were analyzed. The results show that the arm support is the key load-bearing component and has significant optimization potential. Subsequently, functional mapping relationships were established among the 14 dimension parameters of the arm support, reducing the number of design variables to six and successfully avoiding component separation or interference during optimization. Through global sensitivity analysis, the height, thickness, and length of the arm body were screened out as the core optimization parameters from six initial design variables. Then, 29 groups of sample points were generated via central composite design (CCD), and a response surface model reflecting the relationships among the arm body’s dimensional parameters, total mass, maximum stress, and maximum deformation was established using the Kriging method. Leave-one-out cross-validation (LOOCV) was performed, and the coefficients of determination (R²) for model fitting were all higher than 0.995, indicating extremely high prediction accuracy. Taking mass and deformation minimization as the optimization objectives, the MOGA algorithm was adopted to perform multi-objective optimization and determine the optimal engineering parameters. Simulation verification was conducted on the optimized arm support, and an eigenvalue buckling analysis was performed simultaneously to verify structural stability. Finally, the proposed optimization method was experimentally verified through mechanical performance tests of the full-scale prototype under symmetric and eccentric loads. The results show that the mass of the optimized arm support is reduced from 217.73 kg to 189.8 kg, with a weight reduction rate of 12.8%. Under an eccentric load of 70,000 N, the maximum deformation of the arm support is 8.9763 mm, the maximum equivalent stress is 314.86 MPa, and the buckling load factor is 6.08, all of which meet the requirements for structural stiffness, strength, and buckling stability. The maximum error between the experimental and finite element results is only 4.64%, verifying the accuracy and reliability of the proposed method. The proposed optimization methodology, validated on a wheeled multifunctional motorized crossing frame, serves as a transferable paradigm for the lightweight design of complex assemblies with coupled dimensional constraints, thereby offering a general reference for the structural optimization of multi-component transmission line equipment, construction machinery, and other multi-component engineering systems. Full article

Renal cell carcinoma (RCC) is the most common kidney cancer, with increasing global incidence. Despite advances with VEGF-targeted tyrosine kinase inhibitors (TKIs) and immunotherapies, therapeutic resistance remains frequent, limiting long-term benefits. This highlights the need for potential biomarkers of tumor aggressiveness and therapeutic candidates, such as glucose-6-phosphate dehydrogenase (G6PD), whose altered expression has been associated with several cancers. We evaluated G6PD gene and protein expression in 121 RCC samples through immunohistochemistry and assessed functional role in vitro approaches. 786-O and ACHN cells were treated with the inhibitor G6PDi-1 and the anti-VEGF cabozantinib/lenvatinib. G6PD mRNA levels were higher in tumors than in non-neoplastic tissues, indicating shorter overall survival in clear cell (ccRCC) and papillary (pRCC) subtypes. Immunolabeling confirmed a higher expression in pRCC and associations with pathological features. CRISPR and RNAi datasets revealed a stronger G6PD dependency in the ccRCC. A high gene expression was observed in lenvatinib non-responder cell lines, and DepMap dose–response curves indicated modest responses to VEGF inhibitors. In vitro, ACHN was more sensitive to VEGF inhibition, particularly cabozantinib, whereas G6PDi-1 had stronger effects in 786-O, impairing viability, migration, and clonogenic capacity. Our findings support G6PD as a biomarker of tumor aggressiveness and G6PDi-1 as a potential therapeutic in RCC models. Full article

Soil salinization severely threatens agricultural sustainability in saline–alkali regions, and high-throughput, efficient screening of salt-tolerant rice varieties is critical to mitigating this threat. Traditional evaluation methods are constrained by low throughput, limited spatiotemporal resolution, and the lack of standardized indicators. To address these gaps, this study established a multi-scale spectral phenotyping framework integrating ground-based hyperspectral, UAV-borne multispectral, and Sentinel-2 satellite remote sensing data for high-throughput screening of salt-tolerant rice. Field experiments were conducted with 12 rice lines at five key growth stages in Ningxia, China, with synchronous ground spectral measurements and UAV image acquisition on the same day for each stage. Five feature selection methods were employed to screen salt stress-sensitive hyperspectral bands, with classification accuracy validated via a Support Vector Machine (SVM) model. The results showed that: (1) rice spectral characteristics varied dynamically across growth stages, and first-order differential transformation effectively amplified subtle spectral variations in stress-sensitive regions; (2) the Minimum Redundancy–Maximum Relevance (mRMR) method outperformed other methods, achieving 100% classification accuracy at key growth stages, with sensitive bands dominated by red edge bands (58.33%); (3) the constructed Salt Stress Index (SIR) showed strong correlations with classical vegetation indices and rice yield, and could clearly distinguish salt-tolerant and salt-sensitive rice varieties, with stable performance against field environmental noise; and (4) band matching between UAV and Sentinel-2 data enabled multi-scale data fusion and regional-scale salt stress monitoring. This framework realizes the transformation from qualitative spectral description to quantitative salt tolerance evaluation, providing standardized technical support for salt-tolerant rice breeding and precision management of saline–alkali lands. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia and insulin resistance, leading to progressive metabolic dysfunction. Flavonoids, such as astragalin, have reported antidiabetic potential; however, their direct effects on pancreatic β-cell ionic mechanisms and insulin secretion remain unclear. This study aimed to investigate the effects of astragalin on glucose uptake, insulin secretion, and membrane ionic currents in pancreatic β-cell lines. Methods: Murine MIN6 and rat INS-1 pancreatic β-cells were used as experimental models. Following astragalin treatment, glucose uptake was quantified by bioluminescence, and insulin secretion was measured by ELISA. Ionic currents were analyzed using the whole-cell patch-clamp technique. Selective pharmacological blockers targeting ATP-sensitive K⁺ channels (KATP), voltage-dependent K⁺ channels (K_v), and L-type voltage-dependent Ca²⁺ channels were applied to elucidate the underlying mechanisms. Results: Astragalin increased glucose uptake in a time-dependent manner, reaching a plateau between 3 and 5 h. Insulin secretion was significantly enhanced after 1 h of exposure to 100 µM astragalin. Patch-clamp recordings demonstrated that astragalin reduced potassium channel currents in pancreatic β-cells. Pharmacological modulation confirmed the involvement of KATP, K_v, and L-type Ca²⁺ channels. Verapamil attenuated the insulinotropic effect, supporting the role of calcium influx in astragalin-induced insulin exocytosis. Conclusions: Astragalin enhances glucose uptake and stimulates insulin secretion in pancreatic β-cells through modulation of potassium and calcium channels, promoting calcium-dependent exocytosis. These findings support its potential as a candidate for antidiabetic therapeutic strategies. Full article

Seasonal environmental conditions can modulate the chemical composition and biological activity of essential oils from medicinal plants. This study investigated the phytochemical profile, antioxidant potential, cytotoxic activity, and cytoprotective effects of Lippia alba essential oils collected during dry and rainy seasons. Gas chromatography analysis revealed that all samples preserved a citral chemotype. Principal Component Analysis (PCA) confirmed citral as the primary discriminant metabolite, while quantitative seasonal variations were mainly associated with minor oxygenated monoterpenes, particularly geraniol, carvone, and nerolidol. The essential oil obtained during the rainy season (A5T–RS) exhibited significantly higher antioxidant activity, as determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, total antioxidant capacity, and hydrogen peroxide scavenging assays. Intracellular reactive oxygen species (ROS) evaluation using the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) method demonstrated that both oils reduced oxidative stress in murine fibroblasts—L929, with enhanced cytoprotective effects observed for A5T–RS. Cytotoxicity assays against non-tumor (murine fibroblast-NIH/3T3, L929, Chinese hamster ovary—CHO-K1) and tumor (human cervical carcinoma—HeLa, and human hepatocellular carcinoma—HepG2) cell lines revealed selective antiproliferative activity, with tumor cells displaying greater sensitivity, particularly to the rainy-season oil. These results demonstrate that seasonal metabolomic modulation enhances the biological performance of L. alba essential oil without altering its chemotypic identity, highlighting the importance of environmental factors in the development of bioactive plant-derived products. Full article

We study a pharmaceutical scheduling problem with a hybrid batch-continuous manufacturing process in a distributed supply chain. The supply chain consists of heterogeneous plants and one distribution center. Each plant adopts an unrelated permutation flowshop layout consisting of a hybrid batch-continuous production line. Each pharmaceutical order is split and produced in multi-production sites located in various regions. The pharmaceutical medicines manufactured by the production sites are directly shipped to a distribution center. To minimize the makespan, we formulate the addressed scheduling problem as a mathematical model. To solve this model, we propose four metaheuristic variants by applying two population-based metaheuristics to two distinct solution structures. We compare the proposed metaheuristics to evaluate their performance in the numerical experiments. Additionally, we present managerial insights through sensitivity analysis. Full article

Saline–alkali land represents an important reserve of arable resources in China, and exploiting its agricultural potential is crucial for ensuring food security. In maize (Zea mays L.), which is moderately sensitive to salt stress, proline serves as a key osmoprotectant, and Δ¹-pyrroline-5-carboxylate synthetase (P5CS), the rate-limiting enzyme in its biosynthesis, plays a vital role in plant stress responses. In this study, the maize ZmP5CS gene family was systematically identified and characterized through comprehensive bioinformatics analyses. Four ZmP5CS homologs were identified, most of which were predicted to localize to chloroplasts. Phylogenetic analysis classified these genes into four major clades. Among them, ZmP5CS4 (GRMZM2G028535) expression was significantly upregulated under salt stress. Association analysis using a natural population of 278 inbred lines revealed that nine SNPs significantly associated with relative P5CS enzyme activity were located within ZmP5CS4. Haplotype analysis further identified a superior haplotype, HapA, carried by 14 inbred lines. Under salt stress, lines carried by HapA exhibited higher P5CS enzyme activity, greater proline accumulation, lower standard evaluation scores, and slightly enhanced salt tolerance compared to lines carried by HapB. Functional validation via transgenic approaches demonstrated that ZmP5CS4 overexpression significantly increased proline content and plant survival under salt stress, whereas knockout of this gene led to heightened salt sensitivity. Collectively, this study elucidates the structure and function of the maize ZmP5CS gene family, establishes the critical role of ZmP5CS4 in the salt stress response, and provides both a theoretical foundation and a candidate gene resource for improving salt tolerance in maize breeding programs. Full article

Background/Objectives: Programmed death ligand 1 (PD-L1) is often overexpressed in triple-negative breast cancer (TNBC), where it helps the tumor evade the immune system and promotes tumor growth. Interleukin-24 (IL-24) is recognized for its anti-tumor activity, although its role in immune regulation remains unclear. In this study, we examined the role of IL-24 in regulating PD-L1 and its anti-cancer activity in TNBC cells. Methods: The study used TNBC cell lines treated with IL-24, delivered via a non-replicating adenovirus vector expressing the IL-24 gene. Assays included MTT for cell viability, Annexin V for apoptosis, Western blot for protein analysis, and qRT-PCR for mRNA analysis. Results: We found that the highly aggressive MDA-MB-231 cells had significantly higher PD-L1 levels. We discovered that treatment with IL-24 reduced cell growth, induced apoptosis, and significantly decreased PD-L1 protein levels in MDA-MB-231 cells. Mechanistically, we identified PKR, also known as eukaryotic translation initiation factor 2 alpha kinase 2, as a key mediator of IL-24–induced PD-L1 suppression. Additionally, doxorubicin, a primary chemotherapy drug used to treat triple-negative breast cancer, decreases PD-L1 expression and increases the sensitivity when combined with IL-24. Conclusions: In this study, we show that IL-24 decreases PD-L1 expression in MDA-MB-231 cells through PKR activation, enhances the anti-tumor effects of Doxorubicin, and may enable lower doses that reduce toxicity and further decrease PD-L1 levels. These findings suggest that IL-24 could serve as a valuable target for therapeutic intervention and suggest that it can improve doxorubicin’s effectiveness against aggressive breast cancer. Full article

Background/Objectives: Acute pelvic pain in pediatric female patients is a common presentation in the emergency setting and poses significant diagnostic challenges. Ultrasonography is the first-line imaging modality, but a substantial proportion of examinations remain inconclusive. Magnetic resonance imaging (MRI) is increasingly used as a second-line modality in this context; however, evidence comparing the diagnostic performance of non-contrast-enhanced and contrast-enhanced MRI protocols in pediatric patients remains limited. The aim of this study was to assess the diagnostic accuracy of MRI in pediatric females with acute pelvic pain after inconclusive ultrasonography and to compare non-contrast-enhanced and contrast-enhanced MRI protocols. Methods: This single-center observational study included pediatric female patients presenting with acute pelvic pain who underwent MRI after inconclusive ultrasonography. MRI examinations were performed using a standardized protocol including non-contrast-enhanced sequences and diffusion-weighted imaging. Administration of contrast material was determined by the attending radiologist according to clinical indications. Three radiologists with different levels of experience independently reviewed all examinations in two separate reading sessions (without and with contrast). Diagnostic performance, interobserver and intraobserver agreement, diagnostic confidence, and examination duration were assessed using a composite clinical reference standard. Results: Eighty-eight patients (mean age, 13.5 years; range, 7–17 years) were included. MRI identified a specific cause of acute pelvic pain in 60 patients (68.2%), with gynecological conditions accounting for 75.0% of positive findings. Hemorrhagic ovarian cysts and adnexal torsion were the most frequent diagnoses. Both non-contrast-enhanced and contrast-enhanced MRI demonstrated high diagnostic accuracy across all readers, with no statistically significant differences in sensitivity or specificity between protocols (p > 0.05). Contrast-enhanced MRI was associated with higher diagnostic confidence for all readers (p < 0.001) but longer examination times. Conclusions: MRI is a reliable second-line imaging modality for evaluating acute pelvic pain in pediatric female patients after inconclusive ultrasonography. Non-contrast-enhanced MRI combined with diffusion-weighted imaging provides robust diagnostic performance in most cases, while contrast-enhanced MRI may be reserved for selected equivocal cases. Full article