Search Results (441,381)

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of cancer with poor clinical outcomes. There is a critical need to identify novel, druggable targets for TNBC to improve therapy response and patient outcomes. Due to their roles in critical processes driving cancer progression, kinases have been a major focus of drug discovery efforts. The role of extracellular signal-regulated kinase 5 (ERK5) in mediating TNBC extracellular matrix (ECM) has previously been described in 2D culture and in vivo. Here, we characterized the impact of ERK5 on breast cancer biology in 2D culture, 3D spheroids, and our 3D breast adipose-macrophysiological system (BA-MaPS). Methods: We assessed migration changes in MDA-MB-231 parental and ERK5-knockout (ERK5-ko) cells cultured in the three in vitro models using transwell, scratch, and spheroid pseudo-migration assays. Differential gene expression among these cell lines in the three platforms was assessed by RNA sequencing and pathway analysis. Stromal remodeling of adipocytes and matrix was evaluated by H&E and Masson’s Trichrome. Results: Across the in vitro models, ERK5 deletion impaired TNBC cell migration. ERK5-mediated transcriptomic changes included genes associated with epithelial-to-mesenchymal transition (EMT) and migration, with further analysis showing significant alterations in core and associated matrisome. Histological staining corroborated the downregulation of collagen with ERK5 depletion in the BA-MaPS. The NFκB pathway was significantly upregulated only in the ERK5-ko 2D-cultured cells, not in 3D spheroids nor the BA-MaPS model. Conclusions: These results indicate a link between ERK5 and TNBC progression through regulation of TME remodeling, EMT, and cell motility. Differences in 2D culture, 3D spheroid, and BA-MaPS underscore the importance of using physiologically relevant models in breast cancer research. Full article

More than 90% of bladder cancers are classified as urothelial carcinomas (UC), with approximately 75% of these cases presenting as non-muscle-invasive bladder cancer (NMIBC). Bacillus Calmette–Guérin (BCG) is the current standard immunotherapy for NMIBC, yet it suffers from limited efficacy, frequent tumor recurrence, and substantial toxicity. These limitations underscore the need for safer, more effective, and accessible alternatives. We investigated whether uropathogenic Escherichia coli (UPEC), a natural inducer of immune responses in the bladder, could serve as a novel intravesical immunotherapeutic agent. Using orthotopic bladder cancer models in both mice (MB49-luc) and rats (AY-27), we evaluated the efficacy, specificity, immune dependence, and safety of formaldehyde-inactivated UPEC strains, including mutants with altered type 1 fimbriae expression. Intravesical administration of inactivated UPEC significantly reduced tumor burden and prolonged survival, outperforming BCG in murine models and demonstrating equivalent efficacy with markedly reduced toxicity in rats. The antitumor effect was T cell-dependent and partially mediated by type I fimbriae, which facilitated tumor-specific adhesion. Notably, systemic (subcutaneous) administration of UPEC abrogated efficacy and increased mortality, emphasizing the necessity of localized bladder delivery. In conclusion, we identify inactivated UPEC as a potent, tumor-targeting, and T cell-dependent immunotherapeutic agent with a superior safety profile compared to BCG. This approach might represent a promising and practical alternative for bladder cancer treatment. Full article

The increasing deployment of Internet of Things (IoT) sensors in precision agriculture has created critical challenges related to wireless communication range, energy efficiency, and data transmission latency, particularly in large-scale rural operations. This systematic survey, conducted following the PRISMA 2020 guidelines, investigates how drones, acting as mobile data collectors and communication gateways, can enhance the performance of agricultural wireless sensor networks (WSNs). The literature search was carried out in the Scopus and IEEE Xplore databases, considering peer-reviewed studies published in English between 2014 and 2025. After duplicate removal, 985 unique articles were screened based on predefined inclusion and exclusion criteria related to relevance, agricultural application, and communication technologies. Following full-text evaluation, 64 studies were included in this review. The survey analyzes how drones can be efficiently integrated with WSNs to improve data collection, addressing technical and operational challenges such as energy constraints, communication range limitations, propagation losses, and data latency. It further examines the primary applications of drone-based data acquisition supporting efficiency and sustainability in agriculture, identifies the most relevant wireless communication protocols and Technologies and discusses their trade-offs and suitability. Finally, it considers how drone-assisted data collection contributes to improved prediction models and real-time analytics in digital agriculture. The findings reveal persistent challenges in energy management, coverage optimization, and system scalability, but also highlight opportunities for hybrid architectures and the use of intelligent reflecting surfaces (IRSs) to improve connectivity. This work provides a structured overview of current research and future directions in drone-assisted agricultural communication systems. Full article

In the filamentous fungus Neurospora crassa, a gene not having a pairing partner during meiosis is seen as a potential intruder and is targeted by a mechanism called meiotic silencing by unpaired DNA (MSUD). MSUD employs core RNA interference (RNAi) components such as the SMS-2 Argonaute, which uses small interfering RNAs (siRNAs) as guides to seek out mRNAs from unpaired genes for silencing. In Drosophila melanogaster, the heat shock protein 70 (Hsp70) chaperone system facilitates the conformational activation of an Argonaute and allows it to load siRNAs. Here, our results demonstrate that an Hsp70 protein in Neurospora interacts with SMS-2 and mediates the silencing of unpaired genes. Full article

Intravenous thrombolysis with recombinant tissue-type plasminogen activator (tPA) remains a keystone of acute ischemic stroke treatment but in a subset of patients is complicated by angioedema, a potentially life-threatening adverse event largely mediated by bradykinin signaling. The unpredictable and idiosyncratic nature of this reaction has long suggested an underlying genetic contribution, yet its molecular architecture has remained poorly characterized. We hypothesized that alteplase-associated angioedema represents a multigenic susceptibility phenotype, arising from the convergence of rare genetic variants across multiple interacting physiological systems rather than from a single causal variant. To explore this hypothesis, we performed clinical exome sequencing in a cohort of 11 patients who developed angioedema following alteplase administration. Rather than identifying a shared pathogenic variant, we observed distinct yet convergent patterns of genetic vulnerability, allowing patients to be grouped according to dominant, but overlapping, biological axes. These included alterations affecting bradykinin regulation (e.g., ACE, SERPING1, XPNPEP2), endothelial structure and hemostasis (e.g., VWF, COL4A1), neurovascular and calcium signaling (e.g., SCN10A, RYR1), and vascular repair or remodeling pathways (e.g., PSEN2, BRCA2). Notably, many of the identified variants were classified as Variant of Uncertain Significance (VUS) or likely benign significance in isolation. However, when considered within an integrated, pathway-based framework, these variants can be interpreted as capable of contributing cumulatively to system level fragility, a phenomenon best described as “contextual pathogenicity”. Under the acute biochemical and proteolytic stress imposed by thrombolysis, this reduced physiological reserve may allow otherwise compensated vulnerabilities to become clinically manifest. Together, these findings support a model in which severe alteplase-associated angioedema appears as an emergent property of interacting genetic networks, rather than a monogenic disorder. This systems level perspective underscores the limitations of gene centric interpretation for adverse drug reactions and highlights the potential value of pathway informed, multi-genic approaches to risk stratification. Such frameworks may ultimately contribute to safer, more personalized thrombolytic decision, while providing a conceptual foundation for future functional and translational studies. Full article

The combination of supported lipid bilayers (SLBs) with the Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) has been proven to be a powerful tool to simultaneously monitor mass and viscoelastic changes related to membrane binding-events. In this work, the above methodology is employed for the study of the interaction of the Early Endosomal Antigen 1 (EEA1) to a model lipid bilayer that mimics the early endosome (EE) membrane, focusing on the membrane composition. Starting with the formation of a lipid bilayer through the vesicles fusion technique, we investigated the formation of SLBs that incorporate phosphatidylinositol 3-phosphate (PI(3)P), a key component for EEA1 binding, in combination with other lipids, e.g., (1,2-dioleoyl-sn-glycero-3)-phosphocholine (DOPC), -phosphoserine (DOPS), -phosphoethanolamine (DOPE), and cholesterol (Chol). The interaction of the full-length coiled-coil EEA1 to the formed SLBs was further studied in real time with the QCM-D and characterized with respect to the lipid composition and pH. Our findings confirm that PI(3)P is essential for the EEA1–membrane interaction, while it was shown that Chol and phosphatidylserine greatly influence the binding event. In fact, including 30% Chol in a PI(3)P (3%):PS (6%) SLB resulted in almost double EEA1 binding than in the absence of Chol. Moreover, we employed the QCM-viscoelastic model available to analyze the QCM-D data with emphasis on the study of the protein conformation. Our results showed that, in our in vitro system, EEA1 is not fully extended and/or highly packed, but is mainly in a bent, distorted conformation with an average size close to 100 nm. This study complements previous works employing in vitro assays, also demonstrating the ability to reconstitute more complex biomimetic EE membranes containing inositol phospholipids on a QCM surface for the study of EEA1 binding. Full article

Although cytoplasmic male sterility (CMS) is well established in eggplant, CMS-based interspecific hybrids with allied species have not yet been reported or studied. In this study, five previously developed CMS-based interspecific F₁ hybrids between eggplant and Solanum aethiopicum Group Aculeatum (=S. integrifolium) and Group Gilo (=S. gilo), together with their parental lines, were morphologically evaluated for 67 seedling, vegetative, floral, and fruit traits, and their heterosis for vegetative growth was studied. Male fertility was assessed based on anther morphology and pollen viability, while female fertility was evaluated through backcrosses to both parents. The hybrids exhibited predominantly intermediate phenotypes and clustered distinctly from parental lines as confirmed by principal component analysis. Remarkable heterosis was observed for most growth-related traits, indicating favorable nuclear–cytoplasmic interactions despite the use of CMS eggplant lines as maternal parents. All hybrids showed complete male sterility, characterized by non-viable pollen and pronounced anther homeotic alterations, the latter indicating CMS-related effects on male fertility. Female fertility was severely reduced, likely due to meiotic irregularities, as evidenced by the failure of most attempted backcrosses. However, successful recovery of BC₁ progeny after backcrossing one CMS-based F₁ hybrid to S. gilo demonstrates partial reproductive compatibility and provides a genetic bridge for CMS introgression into S. gilo. These results indicate that CMS systems are suitable for eggplant interspecific crosses aimed at vigorous rootstock production and CMS cytoplasm introgression into allied germplasm. Full article

Current research on glial cells has primarily focused on central nervous system glial cells (CNS glia), with relatively fewer studies on EGCs. Given the critical role of EGCs in maintaining intestinal homeostasis and neural function, this study aimed to investigate their immunomodulatory effects under inflammatory conditions. Primary EGCs were isolated and an inflammatory model was established by treatment with lipopolysaccharide (LPS). Following LPS induction, cellular samples were collected for transcriptomic analysis to identify differentially expressed genes. The analysis revealed that 88 genes were significantly altered, with 60 upregulated and 28 downregulated. Through Gene Ontology (GO) classification, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping, and protein–protein interaction (PPI) network analysis, several key regulatory genes were identified: chemokine-related genes (IL8L2, IL8L1, CCL4, CCL5, and CX3CL1); negative feedback regulation-related genes (TNFAIP3 and ZC3H12A); homeostasis-maintaining genes (C1QB and LY86); and arachidonic acid metabolism-related genes (PTGS2 and GGT2). Under LPS stimulation without impairing EGC viability, EGCs may recruit immune cells by regulating the aforementioned genes. Additionally, arachidonic acid and its metabolites likely play important regulatory roles in EGC-mediated immunomodulation. These findings provide new theoretical insights and potential targets for further elucidating the pathogenesis of intestinal inflammation and developing targeted therapies. Full article

Cyclodextrins and chitosan are biomaterials largely used as pharmaceutical excipients due to their biocompatibility, biodegradability, and low/absent toxicity, associated with a number of favorable properties. In particular, cyclodextrins complexation is mainly utilized to improve the physicochemical and biological properties of drugs, including solubility, stability, and bioavailability, and to reduce their irritating effect. Nevertheless, some disadvantages related to the fast removal of the complex from blood circulation after in vivo administration, and possible competition effects for interaction with cyclodextrin between the complexed drug and other molecules present in the biological environment, can reduce their efficacy as drug carriers. On the other hand, chitosan is widely employed to take advantage of its mucoadhesive, controlled/targeted release, and permeation-enhancing properties. However, its almost complete insolubility in water and poor affinity towards hydrophobic molecules (as most drugs are) are considered its main drawbacks, which could strongly limit its applicability. Due to the several beneficial properties of both cyclodextrins and chitosan, their joint use could provide additional favorable effects in drug delivery and help overcome their disadvantages, in particular by combining the complexing/solubilizing ability of the former towards hydrophobic molecules with the mucoadhesive and controlled/targeted release properties of the latter. The present review is intended to provide a critical and comprehensive summary of the main relevant investigations performed in the last twenty-five years regarding the applications and possible advantages that can be obtained by the combined use of cyclodextrins and chitosan in the development of more effective drug delivery systems. Full article

Water resource monitoring can provide beneficial information supporting water management; however, present operational systems are small and provide only a subset of the information needed. Primary advancements consist of the clear explanation of water redistribution and water use from groundwater and river schemes, achieving better spatial detail and increased precision as evaluated against hydrometric observation. In such cases, Earth Observation (EO) satellite systems are persistently creating extensive data, which is now essential for applications in different fields. With readily available open-source satellite imagery, aerial remote sensing is progressively becoming a quick and efficient tool for monitoring land and water resource development actions, demonstrating time and cost savings. At present, the deep learning (DL) model will be beneficial for monitoring water resources and EO utilizing remote sensing. In this paper, a Deep Neural Network-Based Object Detection for Water Resource Monitoring and Earth Observation (DNNOD-WRMEO) model is introduced. The main intention is to develop an effective monitoring and analysis framework for water resources and Earth surface observations using aerial remote sensing images. Initially, the Wiener filter (WF) model was used for image pre-processing. For object detection, the Yolov12 method was used for identifying, locating, and classifying objects within an image, followed by the DNNOD-WRMEO methodology, which implements the ResNet-CapsNet model for the backbone feature extraction method. Finally, the temporal convolutional network (TCN) model was implemented for the classification of water resources. The comparison analysis of the DNNOD-WRMEO methodology exhibited a superior accuracy value of 98.61% compared with existing models under the AIWR dataset. Full article

Sustainable agriculture increasingly relies on biostimulants like protein hydrolysates (PHs) to enhance crop resilience. This study characterized and compared three plant-derived PHs (PH1, PH2, and PH3) from the Malvaceae, Brassicaceae, and Fabaceae families, respectively, under optimal (40 µM Fe³⁺-EDTA) and iron (Fe)-deficient (4 µM Fe³⁺-EDTA) conditions. Initial assays demonstrated that the PHs possessed significant antioxidant capacity and influenced biological activity: PH2 and PH3 promoted pollen germination, while PH1 exhibited a weaker stimulatory effect. In vivo experiments on tomato plants revealed that PH application effectively modulated root architecture and biomass accumulation. Moreover, PH2 and PH3 significantly mitigated Fe deficiency’s impact, by maintaining biomass and preventing chlorosis. Interestingly, while Fe deficiency typically triggers massive root Fe³⁺-chelate reductase activity, PH treatments, particularly PH2, significantly down-regulated this response. This suggests that PHs may improve internal Fe use efficiency or facilitate alternative uptake pathways. Overall, these findings establish a link between the intrinsic bioactive properties of PHs and their biostimulant action, highlighting their potential as innovative tools for improving nutrient use efficiency and crop resilience in sustainable farming systems. Full article

Background/Objectives: The rhizome of Gastrodia elata Blume (Tianma) is a functional food with medicinal value in China, used to improve the health of the central nervous system and reported to exhibit anti-cellular senescent activity. P-hydroxybenzaldehyde (P-HBA) is a key aromatic compound isolated from Tianma; however, its potential to mitigate cellular senescence remains unclear. Methods: We employed ultra-performance liquid chromatography-mass spectrometry to identify the chemical characterization of Tianma extract. Cell viability assay, senescence-associated-β-galactosidase (SA-β-Gal) assay, and immunofluorescence staining and autophagy analysis were used to evaluate the anti-senescent activity of P-HBA and other Tianma components. Results: Our findings demonstrate that Tianma methanol extract (TME) and P-HBA significantly reduce cellular senescent inducer hydroxyurea (HU)-induced DNA damage, SA-β-Gal activity increase, and autophagic dysfunction in human SH-SY5Y cells. Notably, an autophagy inhibitor, chloroquine, can reduce anti-cellular senescent activity of P-HBA. Conclusions: These results suggest that P-HBA exhibits the effect of reducing cellular senescent phenotypes, and its effect is achieved by enhancing autophagy. Full article