Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

Valorization of Al slag in the production of green ceramic tiles: Effect of experimental conditions on microstructure and crystalline phase composition

This work reports the results of an investigation aimed at the development of sintered glass-ceramic tiles by the sinter-crystallization of mixtures composed of aluminum slag and reclaimed packaging glass. The thermal behaviors of mixtures incorporating 50 and 60 wt% Al slag were established by differential thermal analysis (DTA). Green compacts were sintered in a temperature range of 800°C-1050°C and then soaked for 10-60 minutes. The mineralogical characterizations of the sintered materials were obtained by X-ray diffraction (XRD). The achieved results indicated that the sintering of aluminum slag and packaging glass reclaimed led to a glass-ceramic material composed mainly of needle-like crystals of wollastonite (CaSiO₃). The bloating of samples during firing was evaluated according to a Cougny predictive diagram. After initial observations and according to bending strength characterizations, sintered tiles prepared from aluminum slag and glassy sand are appropriate for floor pavement and wall covering.     

DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Exploring New Potential Anticancer Activities of the G-Quadruplexes Formed by [(GTG2T(G3T)3] and Its Derivatives with an Abasic Site Replacing Single Thymidine

In this paper, we report our investigations on five {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 analogues, prepared by replacing sequence thymidines with abasic sites (S) one at a time, in comparison to their natural counterpart in order to evaluate their antiproliferative potential and the involvement of the residues not belonging to the central core of stacked guanosines in biological activity. The collected NMR (Nuclear Magnetic Resonance), CD (Circular Dichroism), and PAGE (Polyacrylamide Gel Electrophoresis) data strongly suggest that all of them adopt G-quadruplex (G4) structures strictly similar to that of the parent aptamer with the ability to fold into a dimeric structure composed of two identical G-quadruplexes, each characterized by parallel strands, three all-anti-G-tetrads and four one-thymidine loops (one bulge and three propeller loops). Furthermore, their antiproliferative (MTT assay) and anti-motility (wound healing assay) properties against lung and colorectal cancer cells were tested. Although all of the oligodeoxynucleotides (ODNs) investigated here exhibited anti-proliferative activity, the unmodified {"type":"entrez-nucleotide","attrs":{"text":"T30175","term_id":"612273"}}T30175 aptamer showed the greatest effect on cell growth, suggesting that both its characteristic folding in dimeric form and its presence in the sequence of all thymidines are crucial elements for antiproliferative activity. This straightforward approach is suitable for understanding the critical requirements of the G-quadruplex structures that affect antiproliferative potential and suggests its application as a starting point to facilitate the reasonable development of G-quadruplexes with improved anticancer properties.     

Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.     

First data from the EGLE experiment onboard the ISS

EGLE is a wide frequency band search- coil magnetometer designed and built at the Roma Tre University. It has been installed onboard the ISS by the Italian astronaut Roberto Vittori on April 25, 2005 within the LAZIO- EGLE experiment carried out during the ENEIDE Soyuz mission. The scope of the experiment is to test EGLE in space and to investigate geomagnetic field variations. The main applications of EGLE are the study of electromagnetic environment inside the ISS, the correlation of magnetic field data with particle fluxes detected by LAZIO particle detector, and the monitoring of ionospheric perturbations possibly caused by Earth seismic activity. Since continuous electromagnetic field measurements on board the ISS are important for diverse space applications, a magnetometer with a suitable design is requested. Appropriate solutions for these applications, which have been adopted by EGLE, are in particular the use of 1- Wire technology and the possibility to detect by means of a search- coil magnetometer a large portion of the ULF frequency band, usually measured by flux- gate probes. To investigate the topside ionosphere electromagnetic environment and stability of Van Allen radiation belts in relation with seismic and anthropogenic electromagnetic emissions, a specific satellite mission (the ESPERIA project) has been designed for the Italian Space Agency (ASI), and up to now a few instruments of its payload have been built and tested in space. One of them is exactly the EGLE search- coil magnetometer. The first magnetic observations performed by this instrument reveal to be promising and demand for a further and deeper analysis based on a longer time series of data.     

Building kernels from binary strings for image matching.

In the statistical learning framework, the use of appropriate kernels may be the key for substantial improvement in solving a given problem. In essence, a kernel is a similarity measure between input points satisfying some mathematical requirements and possibly capturing the domain knowledge. In this paper, we focus on kernels for images: we represent the image information content with binary strings and discuss various bitwise manipulations obtained using logical operators and convolution with nonbinary stencils. In the theoretical contribution of our work, we show that histogram intersection is a Mercer's kernel and we determine the modifications under which a similarity measure based on the notion of Hausdorff distance is also a Mercer's kernel. In both cases, we determine explicitly the mapping from input to feature space. The presented experimental results support the relevance of our analysis for developing effective trainable systems.     

Promoting the integration of technology in teaching: An analysis of the factors that increase the intention to use technologies among Italian teachers

Background: The rapid spread of COVID-19 forced many countries to adopt severe containment measures, transferring all didactic activities into virtual environments. However, the integration of technology in teaching may present difficulties, especially in some countries, such as Italy. Objectives: The present study analyzed how the two main factors of the Technology Acceptance Model (TAM), namely perceived usefulness and perceived ease of use, combined with online teaching self-efficacy, were associated with the intention to use technology to teach. We posited a moderated moderation model in which perceived usefulness represented the main predictor, with self-efficacy and perceived ease of use as moderators of intention to use technology to teach. Method: The model was tested through multiple regressions, using the PROCESS macro on SPSS 26 with a sample of 178 upper secondary school teachers in Italy. Results and conclusions: Regressions showed that each variable significantly predicted the intention to use technology. In addition, a moderation effect of self-efficacy on the perceived usefulness of using technology was found for medium and high-level of perceived ease of use of technology. Implications: The present study provides targeted implications for distance education policy and practice to promote its adoption (or the blended modality) in Italian upper schools.