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We delineated the signaling of ponatinib-induced vascular toxicity, demonstrating that ponatinib inhibits endothelial survival, reduces angiogenesis and induces endothelial senescence and apoptosis via the Notch-1 pathway. Ponatinib induced endothelial toxicity in vitro. Hyperactivation of Notch-1 in the vessels can lead to abnormal vascular development and vascular dysfunction. By hyperactivating Notch-1 in the vessels, ponatinib exerts an "on-target off tumor effect", which leads to deleterious effects and may explain the drug's vasculotoxicity. Selective blockade of Notch-1 prevented ponatinib-induced vascular toxicity.The revolution in the global market of composite materials is evidenced by their increasing use in such segments as the transport, aviation, and wind industries. Puromycin aminonucleoside supplier The innovative aspect of this research is the methodology approach, based on the simultaneous analysis of mechanical and tribological loads of composite materials, which are intended for practical use in the construction of aviation parts. Simultaneously, the methodology allows the composition of the composites used in aviation to be optimized. Therefore, the presented tests show the undefined properties of the new material, which are necessary for verification at the application stage. They are also a starting point for further research planned by the authors related to the improvement of the tribological properties of this material. In this article, the selected mechanical and tribological properties of an aviation polymer composite are investigated with the matrix of L285-cured hardener H286 and six reinforcement layers of carbon fabric GG 280P/T. The structure of a polymer composite has a significant influence on its mechanical properties; thus, a tribological analysis in the context of abrasive wear in reciprocating the movement for the specified polymer composite was performed. Moreover, the research was expanded to dynamic analysis for the discussed composite. This is crucial knowledge of material dynamics in the context of aviation design for the conditions of resonance vibrations. For this reason, experimental dynamical investigations were performed to determine the basic resonance of the material and its dynamics behavior response. The research confirmed the assumed hypotheses related to the abrasive wear process for the newly developed material, as well as reporting an empirical evaluation of the dependencies of the resonance zone from the fabric orientation sets.The fact that a single bout of acute physical exercise has a positive impact on cognition is well-established in the literature, but the neural correlates that underlie these cognitive improvements are not well understood. Here, the use of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), offers great potential, which is just starting to be recognized. This review aims at providing an overview of those studies that used fMRI to investigate the effects of acute physical exercises on cerebral hemodynamics and cognition. To this end, a systematic literature survey was conducted by two independent reviewers across five electronic databases. The search returned 668 studies, of which 14 studies met the inclusion criteria and were analyzed in this systematic review. Although the findings of the reviewed studies suggest that acute physical exercise (e.g., cycling) leads to profound changes in functional brain activation, the small number of available studies and the great variability in the study protocols limits the conclusions that can be drawn with certainty. In order to overcome these limitations, new, more well-designed trials are needed that (i) use a more rigorous study design, (ii) apply more sophisticated filter methods in fMRI data analysis, (iii) describe the applied processing steps of fMRI data analysis in more detail, and (iv) provide a more precise exercise prescription.(1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic responses induced by titanium dioxide (TiO2), silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) in 2D monolayer and 3D spheroid cultures of HepG2 human liver cells. (2) NPs were characterized by electron microscopy, dynamic light scattering, laser Doppler anemometry, UV-vis spectroscopy and mass spectrometry. Cytotoxicity was investigated by the alamarBlue assay and confocal microscopy in HepG2 monolayer and spheroid cultures after 24 h of NP exposure. DNA damage (strand breaks and oxidized base lesions) was measured by the comet assay. (3) Ag-NPs were aggregated at 24 h, and a substantial part of the ZnO-NPs was dissolved in culture medium. Ag-NPs induced stronger cytotoxicity in 2D cultures (EC50 3.8 µg/cm2) than in 3D cultures (EC50 > 30 µg/cm2), and ZnO-NPs induced cytotoxicity to a similar extent in both models (EC50 10.1-16.2 µg/cm2). Ag- and ZnO-NPs showed a concentration-dependent genotoxic effect, but the effect was not statistically significant. TiO2-NPs showed no toxicity (EC50 > 75 µg/cm2). (4) This study shows that the HepG2 spheroid model is a promising advanced in vitro model for toxicity assessment of NPs.Transthyretin (TTR), an homotetrameric protein mainly synthesized by the liver and the choroid plexus, and secreted into the blood and the cerebrospinal fluid, respectively, has been specially acknowledged for its functions as a transporter protein of thyroxine and retinol (the latter through binding to the retinol-binding protein), in these fluids. Still, this protein has managed to stay in the spotlight as it has been assigned new and varied functions. In this review, we cover knowledge on novel TTR functions and the cellular pathways involved, spanning from neuroprotection to vascular events, while emphasizing its involvement in Alzheimer's disease (AD). We describe details of TTR as an amyloid binding protein and discuss its interaction with the amyloid Aβ peptides, and the proposed mechanisms underlying TTR neuroprotection in AD. We also present the importance of translating advances in the knowledge of the TTR neuroprotective role into drug discovery strategies focused on TTR as a new target in AD therapeutics.