Search Results (577)

Accurate and spatially consistent rainfall estimation is essential for hydrological modeling and flood risk mitigation, especially in mountainous tropical regions with sparse observational networks and highly heterogeneous rainfall. This study presents a comparative analysis of six radar–gauge merging methods, including three statistical approaches—Quantile Adaptive Gaussian (QAG), Empirical Quantile Mapping (EQM), and radial basis function (RBF)—and three geostatistical approaches—external drift kriging (EDK), Bayesian Kriging (BAK), and Residual Kriging (REK). The evaluation was conducted over the Huong River Basin in Central Vietnam, a region characterized by steep terrain, monsoonal climate, and frequent hydrometeorological extremes. Two observational scenarios were established: Scenario S1 utilized 13 gauges for merging and 7 for independent validation, while Scenario S2 employed all 20 stations. Hourly radar and gauge data from peak rainy months were used for the evaluation. Each method was assessed using continuous metrics (RMSE, MAE, CC, NSE, and KGE), categorical metrics (POD and CSI), and spatial consistency indicators. Results indicate that all merging methods significantly improved the accuracy of rainfall estimates compared to raw radar data. Among them, RBF consistently achieved the highest accuracy, with the lowest RMSE (1.24 mm/h), highest NSE (0.954), and strongest spatial correlation (CC = 0.978) in Scenario S2. RBF also maintained high classification skills across all rainfall categories, including very heavy rain. EDK and BAK performed better with denser gauge input but required recalibration of variogram parameters. EQM and REK yielded moderate performance and had limitations near basin boundaries where gauge coverage was sparse. The results highlight trade-offs between method complexity, spatial accuracy, and robustness. While complex methods like EDK and BAK offer detailed spatial outputs, they require more calibration. Simpler methods are easier to apply across different conditions. RBF emerged as the most practical and transferable option, offering strong generalization, minimal calibration needs, and computational efficiency. These findings provide useful guidance for integrating radar and gauge data in flood-prone, data-scarce regions. Full article

The B-cell lymphoma 2 (Bcl-2)-related ovarian killer (BOK), a member of the Bcl-2 protein family, shares a similar domain structure and amino acid sequence homology with the pro-apoptotic family members BAX and BAK. Although BOK is involved in the development of various types of cancer, its mechanism of action in breast cancer remains unclear. This study found that BOK was involved in the process of MG132, inhibiting the migration and epithelial–mesenchymal transition (EMT) of breast cancer cells induced by transforming growth factor-β. Furthermore, interfering BOK reversed the inhibition of breast cancer cell migration and the EMT process by MG132. Additional studies revealed that BOK silencing promoted the expression of EMT-related markers in breast cancer cells, while BOK overexpression inhibited EMT and migration. Using RNA-seq sequencing and Western blotting, we confirmed that the Wnt signaling pathway is involved in BOK regulating the EMT process in breast cancer cells. Therefore, we conclude that low BOK expression promotes breast cancer EMT and migration by activating the Wnt signaling pathway. This study enhances our understanding of breast cancer pathogenesis and suggests that BOK may serve as a potential prognostic marker and therapeutic target for breast cancer. Full article

Background: The treatment landscape for multiple myeloma (MM) has significantly evolved in recent decades with novel therapies like proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. However, MM remains incurable, necessitating new pharmacological strategies. Mitotic kinases, such as Aurora proteins, have emerged as potential targets. Selective inhibitors of Aurora A and B,- alisertib (MLN8237) and barasertib (AZD1152), respectively, have shown anti-myeloma activity in preclinical studies, with alisertib demonstrating modest efficacy in early clinical trials. Methods and Results: This study investigated the mechanisms of action of alisertib and barasertib and their combination with antitumor agents in a panel of five MM cells lines. Both drugs induced cell cycle arrest phase and abnormal nuclear morphologies. Alisertib caused prolonged mitotic arrest, whereas barasertib induced transient arrest, both resulting in the activation of mitotic catastrophe. These findings revealed three potential outcomes: cell death, senescence, or polyploidy. High mitochondrial reactive oxygen species (mROS) were identified as possible drivers of cell death. Caspase inhibition reduced caspase-3 activation but did not prevent cell death. Interestingly, alisertib at low doses remained toxic to Bax/Bak^DKO cells, although mitochondrial potential disruption and cytochrome c release were observed. Sequential combinations of high-dose Aurora kinase inhibitors with BH3-mimetics, and in specific cases with panobinostat, showed a synergistic effect. Conversely, the simultaneous combination of alisertib and barasertib showed mostly antagonistic effects. Conclusions: Alisertib and barasertib emerge as potential in vitro candidates against MM, although further studies are needed to validate their efficacy and to find the best combinations with other molecules. Full article

Springtails are adapted to life in the pore space of soil, where humidity in moist soil is close to saturation. Drought is the most important limiting factor for springtails; however, their molecular and physiological adaptations to low humidity are not well understood. The present study explored the global proteomic drought response of the springtail, Folsomia candida (Isotomidae, Collembola). In relatively dry soil (−360 kPa), adult springtails initially lost body water but re-established the normal body water content over the following two weeks. Nano LC–MS/MS analysis identified a total of 1729 unique proteins. Proteomic analysis and pathway enrichment found that the proteome generally did not show a dramatic induction of proteins in response to drought stress. After an initial down-regulation of pathways related to metabolism and growth, these pathways gradually returned to the same levels as in moist soil. Other pathways such as the cytoskeleton pathway, which is important in cell proliferation and differentiation, were predominantly down-regulated throughout the experiment in drought-exposed animals, which correlated with essentially no somatic growth of the springtails in dry soil. This study facilitates the understanding of the consequences of climate change on soil functioning and fertility. Full article

The resistance of breast cancer cells to therapeutic antibodies such as anti-HER2 trastuzumab can be overcome by engaging natural killer (NK) cells for killing antibody-binding tumor cells via antibody-dependent cellular cytotoxicity (ADCC). Here, we investigated how autophagy modulation affects trastuzumab-mediated ADCC in HER2-positive JIMT1 breast cancer cells and NK cells. Autophagy inducers (rapamycin and resveratrol) had no significant impact, but the inhibitor bafilomycin nearly abolished ADCC. Protection occurred when either cancer or NK cells were pretreated, indicating dual effects. Bafilomycin reduced phosphatidylserine externalization, the loss of plasma membrane integrity, caspase-3/7 activity, and DNA fragmentation. It downregulated pro-apoptotic BAK1 and BAX without altering BCL-2. Additionally, bafilomycin decreased HER2 surface expression, impairing trastuzumab binding, and modulated immune regulators (STAT1, CD95, and PD-L1) in NK and/or in the cancer cells. Bafilomycin disrupted HER2 trafficking and induced HER2 internalization, leading to its accumulation in cytoplasmic vesicles. These findings show that autophagy inhibition by bafilomycin confers ADCC resistance by altering apoptosis, immune signaling, and HER2 dynamics. The study underscores autophagy’s role in antibody-based cancer therapy efficacy. Full article

Ovarian cancer cells overexpress HDAC6, and selective HDAC6 inhibitors have been considered potential new drugs for ovarian cancer either alone or in combination with other anticancer agents. We screened 46 potential novel HDAC6 inhibitors in ES-2 ovarian cancer cells and showed that compound 25253 demonstrated the most potent anti-proliferative activity and effective synergy with paclitaxel, which was also validated in TOV21G ovarian cancer cells. The combination of 25253 and paclitaxel significantly induced subG1 and apoptotic cells, revealed by PI staining assay and Annexin V-FITC/PI double staining assay, respectively. Western blot analysis showed downregulation of Bcl-2 and Bcl-XL, and upregulation of Bax and Bak, indicating that apoptosis was mediated through the intrinsic pathway. The combination increased γ-H2AX and p-p53 protein levels, suggesting the induction of DNA damage. Furthermore, HDAC6 was downregulated and acetylated α-tubulin was profoundly increased. Compound 25253 enhanced the inhibitory effect of paclitaxel on cell migration and invasion, possibly due to the extensive accumulation of acetylated α-tubulin, which affected microtubule dynamics. Taken together, the combination of 25253 and paclitaxel synergistically inhibited the growth, migration, and invasion of ovarian cancer cells and induced apoptosis, providing supporting evidence that the combination of HDAC6 inhibitors and paclitaxel may be a promising treatment strategy for ovarian cancer. Full article

Mesenchymal stem cells (MSCs) have recently shown great promise as potential anticancer drug delivery carriers. MSCs exhibit tropism to inflammatory sites, such as tumor beds, and resistance to chemotherapeutics. The aim of this study was to examine the efficacy of gemcitabine (GEM) conjugated with flurbiprofen (FLU) as a potential agent enhancing the GEM cytotoxic effect. Pancreatic cancer cell lines (PCCs), including PANC-1, AsPC-1, and BxPC-3, were studied meticulously. Moreover, the usefulness of bone-marrow-derived mesenchymal stem cells (BM-MSCs) treated with GEM and FLU, and the conditioned media from above these cells (CM) as elements supporting the in vitro action of GEM, inducing apoptosis, necrosis, and inhibiting the cell cycle, was tested. The results showed that CM-GEM exhibited higher cytotoxicity towards the selected PCCs compared to GEM alone. Furthermore, the obtained data revealed lower sensitivity of these cells to treatment, which promotes the utilization of BM-MSCs as potential drug carriers. Based on the presented findings, it seems that applying FLU in the antiproliferative effect of GEM might be regarded as an effective strategy in the therapy of pancreatic cancer, especially in the inhibition of proliferation and induction of cancer cell death. Full article

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect of cancer treatment. Characterized by symptoms like pain, numbness, and muscle weakness, CIPN significantly impacts patients’ quality of life. Current management strategies vary, with limited consensus on effective treatments. This scoping review aims to explore comprehensive rehabilitation interventions for CIPN, focusing on enhancing patient well-being and functional abilities. Methods: A scoping review, guided by Arksey and O’Malley’s framework and Levac et al.’s refinements, was conducted to assess rehabilitation programs for CIPN. Searches across six databases were performed, with inclusion and exclusion criteria focusing on studies with physical rehabilitation interventions. Data were charted, detailing interventions, demographics, and outcomes. Results were synthesized descriptively and presented narratively with tables. Results: The review included 24 studies covering diverse cancer types and treatments, involving a total of 1167 participants. Various interventions for CIPN were assessed, and results were thematically categorized according to exercise category. Physical modalities like ultrasound and exercise showed promise in symptom relief for colorectal and breast cancer patients. No distinct advantage was found in the timing of exercise interventions. Complementary therapies such as acupuncture and yoga demonstrated effectiveness in managing CIPN symptoms. Conclusions: This review highlights the effectiveness of diverse physical and complementary interventions in managing CIPN, advocating for their integration into standard protocols. It emphasizes the need for holistic, patient-centered approaches that combine exercises, physical therapy, and complementary therapies to improve patient outcomes. These findings set a direction for future research and clinical practices focused on comprehensive and personalized CIPN management strategies. Full article

Mitochondrial transplantation (MTx) has emerged as a potential therapeutic approach for diseases associated with mitochondrial dysfunction, yet its scalability and cross-species feasibility remain underexplored. This study aimed to evaluate the dose-dependent uptake and molecular effects of xenogeneic mitochondrial transplantation (xeno-MTx) using rat-derived mitochondria in mouse neuronal systems. HT-22 hippocampal neuronal cells and a murine model of cardiac arrest-induced global cerebral ischemia were used to assess mitochondrial uptake, gene expression, and mitochondrial DNA presence. Donor mitochondria were isolated from rat pectoralis muscle and labeled with MitoTracker dyes. Flow cytometry and confocal microscopy revealed a dose-dependent increase in donor mitochondrial uptake in vitro. Quantitative PCR demonstrated a corresponding increase in rat-specific mitochondrial DNA and upregulation of Mfn2 and Bak1, with no changes in other fusion, fission, or apoptotic genes. Inhibitor studies indicated that mitochondrial internalization may involve actin-dependent macropinocytosis and cholesterol-sensitive endocytic pathways. In vivo, rat mitochondrial DNA was detected in mouse brains post–xeno-MTx, confirming donor mitochondrial delivery to ischemic tissue. These findings support the feasibility of xeno-MTx and its dose-responsive biological effects in neuronal systems while underscoring the need for further research to determine long-term functional outcomes and clinical applicability. Full article

This study developed a transparent NO₂ gas sensor with enhanced sensing performance and high optical transmittance. Al-doped ZnO thin films were deposited by atomic layer deposition, which was chosen for its capability to precisely control surface chemistry at the atomic scale. Oxygen vacancies were effectively introduced by utilizing trimethylaluminum, a strongly reducing Al₂O₃ precursor, thereby increasing carrier concentration and enhancing gas-sensing performance. By adjusting the Al doping level, the optimized device achieved a 50 °C reduction in operating temperature, a 66.2-fold increase in sensitivity at 150 °C, and shortened response and recovery times. The morphology, crystallinity, and elemental distribution were analyzed using transmission electron microscopy, selected area electron diffraction, and energy-dispersive X-ray spectroscopy, while chemical bonding states were investigated via X-ray photoelectron spectroscopy. Optical properties were characterized using UV–visible spectroscopy, confirming an average transmittance of approximately 80% in the visible range. These results demonstrate the promise of transparent oxide gas sensors for integration into next-generation electronics and Internet of Things-based environmental monitoring systems. Full article

Breast cancer (BC) remains a significant therapeutic challenge, necessitating novel agents with multi-target efficacy. Here, we demonstrate that triptophenolide (TRI), a bioactive compound from Tripterygium wilfordii, exerts potent anti-BC activity across hormone-responsive (MCF-7) and triple-negative (MDA-MB-231) subtypes. In vitro, TRI inhibited proliferation in a concentration-dependent manner, with IC₅₀ values decreasing from 180.3 μg/mL (24 h) to 127.2 μg/mL (48 h) in MCF-7 cells, and from 322.5 μg/mL to 262.1 μg/mL in MDA-MB-231 cells. TRI treatment induced G1-phase arrest in both breast cancer subtypes, increasing the G1 population by 22.27% in MCF-7 cells and 10.64% in MDA-MB-231 cells. Concurrently, TRI triggered apoptosis, elevating apoptotic rates from 3.36% to 9.78% in MCF-7 cells and from 7.01% to 17.02% in MDA-MB-231 cells. These effects were associated with the significant upregulation of pro-apoptotic proteins BAX, BAK1, BIM, and cytochrome c (CYCS). Notably, TRI suppressed migration by 61.5% (MCF-7) and 71.5% (MDA-MB-231). In vivo, TRI treatment inhibited MCF-7 xenograft growth and reduced tumor volume (1207.5 vs. 285 mm³) and weight (0.22 vs. 0.1 g), while extending the survival time of tumor-bearing mice from 14–20 days to 24 days. These results position TRI as a promising lead therapeutic candidate against diverse BC subtypes, with mechanistic versatility surpassing single-target agents. Full article

Background: Human Immunodeficiency Virus (HIV) infections remain a source of cardiopulmonary complications among people receiving antiretroviral therapy. Still to this day, pulmonary hypertension (PH) severely affects the prognosis in this patient population. The persistent expression of HIV proteins, even during viral suppression, has been implicated in vascular dysfunction; however, little is known about the specific effects of these proteins on the pulmonary vasculature. This study investigates the impact of Nef variants derived from HIV-positive pulmonary hypertensive and normotensive donors on pulmonary vascular cells in vitro. Methods: We utilized well-characterized Nef molecular constructs to examine their effects on cell adhesion molecule gene expression (ICAM1, VCAM1, and SELE), pro-apoptotic gene expression (BAX, BAK), and vasoconstrictive endothelin-1 (EDN1) gene expression in endothelial nitric oxide synthase (eNOS) nitric oxide and the production and secretion of pro-inflammatory cytokines over 24, 48, and 72 h post-transfections with Nef variants. Results: HIV Nef variants SF2, NA7, and PH-associated Fr17 and 3236 induced a significant increase in adhesion molecule gene expression of ICAM1, VCAM1, and SELE. Pulmonary normotensive Nef 1138 decreased ICAM1 gene expression, but had increased VCAM1. PH Nef ItVR showed a consistent decrease in ICAM1 and no changes in SELE and VCAM1 expression. Further gene expression analyses of pro-apoptotic genes BAX and BAK demonstrated that Nef NA7, SF2, normotensive Nef 1138, and PH Nef Fr8, Fr9, Fr17, and 3236 variants significantly increased gene expression for apoptosis. Normotensive Nef 1138, as well as PH Nef Fr9 and ItVR, all displayed a statistically significant decrease in BAX expression. The expression of EDN1 had a statistically significant increase in samples treated with Nef NA7, SF2, normotensive Nef 2044 and PH Nef 3236, Fr17, and Fr8. Notably, PH-associated Nef variants sustained pro-inflammatory cytokine production, including IL-2, IL-4, and TNFα, while anti-inflammatory cytokine levels remained insufficient. Furthermore, eNOS was transiently upregulated by all Nef variants except for normotensive Nef 2044. Conclusions: The distinct effects of Nef variants on pulmonary vascular cell biology highlight the complex interplay between Nef, host factors, and vascular pathogenesis according to the variants. Full article

Driven by increased integration of renewable energy sources, the widespread decarbonization of power systems has led to energy price fluctuations that require greater adaptability and flexibility from grid users in order to maximize profits. Industrial loads equipped with flexible resources can optimize energy consumption rather than merely reacting to immediate events, thereby capitalizing on volatile energy prices. However, the absence of sufficient measured data in industrial processes limits the ability to fully harness this flexibility. To address this challenge, we presents a black-box optimization model for optimizing the energy consumption of cooling systems in the aquaculture industry using Extreme Gradient Boosting (XGBoost) and Bayesian Optimization (BO). XGBoost is employed to establish a nonlinear relationship between cooling system power consumption and available measured data. Based on this model, Bayesian Optimization with the Lower Confidence Bound (LCB) acquisition function is used to determine the optimal discharge temperature of water into breeding pools, minimizing day-ahead electricity costs. The proposed approach is validated using real-world data from a case study at the Port of Hirtshals, Denmark based on measurements from 2023. Our findings illustrate that leveraging the inherent flexibility of industrial processes can yield financial benefits while providing valuable signals for grid operators to adjust consumption behaviors through appropriate price mechanisms. Furthermore, machine learning techniques prove effective in optimizing energy consumption for industries with limited measured data, delivering accurate and practical estimations. Full article

The surge in electric vehicles (EVs) in Denmark challenges the country’s residential low-voltage (LV) distribution system. In particular, it increases the demand for home EV charging significantly and possibly overloads the LV grid. This study analyzes the impact of EV charging integration on Denmark’s residential distribution networks. A residential grid comprising 67 households powered by a 630 kVA transformer is studied using DiGSILENT PowerFactory. With the assumption of simultaneous charging of all EVs, the transformer can be heavily loaded up to 147.2%. Thus, a voltage-droop based autonomous control approach is adopted, where the EV charging power is dynamically adjusted based on the point-of-connection voltage of each charger instead of the fixed rated power. This strategy eliminates overloading of the transformers and cables, ensuring they operate within a pre-set limit of 80%. Voltage drops are mitigated within the acceptable safety range of ±10% from normal voltage. These results highlight the effectiveness of the droop control strategy in managing EV charging power. Finally, it exemplifies the benefits of intelligent EV charging systems in Horizon 2020 EU Projects like SERENE and SUSTENANCE. The findings underscore the necessity to integrate smart control mechanisms, consider reinforcing grids, and promote active consumer participation to meet the rising demand for a low-carbon future. Full article

Marssonina coronaria is the causal agent of apple blotch, which poses a significant threat to apple production worldwide. Here, Illumina and Oxford Nanopore sequencing were combined to generate a high-quality M. coronaria YL1 genome assembly (54.5 Mb, 23 contigs). Based on genome annotation, 97 candidate effector proteins (CEPs) were identified, and 61 CEPs were successfully cloned for functional analysis. Transient expression assays in Nicotiana benthamiana revealed that eight CEPs significantly suppressed BAX-induced cell death, with McCEP12, McCEP23, McCEP24, and McCEP52 concurrently inhibiting flg22-triggered reactive oxygen species bursts. Two signal peptide-dependent cell death-inducing effectors were identified: McNLP1, containing an NPP1 domain, and McCEP3. McCEP3 exhibited evolutionary conservation within Ascomycota, with its homologous gene VmMcCEP3 from Valsa mali inducing cell death in N. benthamiana. McEP03-triggered cell death was independent of BAK1/SOBIR1 receptor kinases. This study provides a high-quality genomic resource for M. coronaria and sheds light on the mechanisms by which its CEPs modulate host immunity, offering new insights into the molecular interactions between the pathogen and its host. Full article