Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.     

Multidrug Idebenone/Naproxen Co-loaded Aspasomes for Significant in vivo Anti-inflammatory Activity

The use of proper nanocarriers for dermal and transdermal delivery of anti-inflammatory drugs recently gained several attentions in the scientific community because they pass intact and accumulate payloads in the deepest layers of skin tissue. Ascorbyl palmitate-based vesicles (aspasomes) can be considered a promising nanocarrier for dermal and transdermal delivery due to their skin whitening properties and suitable delivery of payloads through the skin. The aim of this study was the synthesis of multidrug Idebenone/naproxen co-loaded aspasomes for the development of an effective anti-inflammatory nanomedicine. Aspasomes had suitable physicochemical properties and were safe in vivo if topically applied on human healthy volunteers. Idebenone/naproxen co-loaded aspasomes demonstrated an increased therapeutic efficacy of payloads compared to the commercially available Naprosyn® gel, with a rapid decrease of chemical-induced erythema on human volunteers. These promising results strongly suggested a potential application of Idebenone/naproxen multidrug aspasomes for the development of an effective skin anti-inflammatory therapy.     

A Power-Supply Unit for Pulsed Lasers without a Storage Capacitor

A power-supply unit for pulsed lasers that are pumped by low- and medium-power flashlamps with long pump pulses that does not require a capacitive storage unit is described. The pump-pulse duration is limited by the radiation and thermal stability of the active elements and pump lamps. A functional diagram of the power-supply unit and a circuit diagram of its power system are presented. The basic parameters and elements of this unit, as well as the results of using a laser with the described power supply in experiments, are presented.     

β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and ¹H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC_50s and EC_90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.     

Design and performance evaluation of ContentPlace,a social-aware data dissemination system for opportunistic networks

In this paper we present and evaluate ContentPlace, a data dissemination system for opportunistic networks, i.e., mobile networks in which stable simultaneous multi-hop paths between communication endpoints cannot be provided. We consider a scenario in which users both produce and consume data objects. ContentPlace takes care of moving and replicating data objects in the network such that interested users receive them despite possible long disconnections, partitions, etc. Thanks to ContentPlace, data producers and consumers are completely decoupled, and might be never connected to the network at the same point in time. The key feature of ContentPlace is learning and exploiting information about the social behaviour of the users to drive the data dissemination process. This allows ContentPlace to be more efficient both in terms of data delivery and in terms of resource usage with respect to reference alternative solutions. The performance of ContentPlace is thoroughly investigated both through simulation and analytical models.     

Foam-like scaffolds for bone tissue engineering based on a novel couple of silicate-phosphate specular glasses: synthesis and properties

Glass–ceramic scaffolds mimicking the structure of cancellous bone were produced via sponge replication technique by using a polyurethane foam as template and glass powder below 30 μm as inorganic phase. Specifically, a SiO₂-based glass of complex composition and its corresponding P₂O₅-based “specular” glass were used as materials for scaffolding. The polymeric sponge was thermally removed and the glass powders were sintered to obtain a replica of the template structure. The scaffolds were investigated and compared from a structural, morphological and mechanical viewpoint by assessing their crystalline phases, volumetric shrinkage, pores content and interconnection, mechanical strength. In addition, the scaffolds were soaked in acellular simulated body fluid to investigate their in vitro behaviour. The produced scaffolds have a great potential for bone reconstructive surgery because their features, such as shape, strength, bioactivity and bioresorption, can be easily tailored according to the end use.     

Vinylene-linked pyridine-pyrrole donor–acceptor conjugated polymers

Vinylene-linked donor–acceptor–donor semiconducting polymers have been prepared by electropolymerization of the new monomers 2,6-bis[(E)-2-(1-methylpyrrol-2-yl)vinyl]pyridine and 2,5-bis[(E)-2-(1-methylpyrrol-2-yl)vinyl]pyridine. The monomers, consisting of two pyrrole donor units and a central pyridine acceptor ring spaced by vinylene links, differ by the substitution pattern around the central pyridine core (2,6 vs. 2,5-substitution). The electropolymerization process is more efficient on the 2,5-derivative. The new polymers show reversible electrochemistry dominated by a strong charge trapping effect. Poly(2,5-bis[(E)-2-(1-methylpyrrol-2-yl)vinyl]pyridine) energy levels closely match those of design rules for optimized polymers in combination with fullerene derivatives in bulk heterojunction solar cells.     

Residual Stresses in Alumina/Zirconia Composites: Effect of Cooling Rate and Grain Size

Alumina/zirconia composites with various compositions at the zirconia-rich part of the phase diagram have been prepared with various grain sizes of the starting alumina powders. After firing under identical conditions, the pellets have been cooled systematically, changing the cooling rates from 0.5 to 8000 K/min. Subsequently, the residual stresses in alumina have been determined by monitoring the frequency shifts of the R ₂ luminescence line of alumina (14 430 cm⁻¹). The data indicate that the stress in alumina is compressive in all cases, with increasing absolute values of the stress with decreasing alumina content. Within the same composition, the residual stress as a function of the cooling rate presents a minimum for values between 10 and 100 K/min, with no clear dependence on the alumina or zirconia grain size. An interpretation of the experimental data in terms of a Coble-type diffusional relaxation applies for intermediate cooling rates (from 10 to 800 K/min), but it fails to account for the large stresses at low cooling rates. The width of the stress distribution is narrow (∼150 MPa) and constant for all compositions and grain sizes at low cooling rates, but it increases for cooling rates >10 K/min, depending on the grain size but not on the composition. For fast cooling rates, a correlation is found when reporting the average width of the stress distribution as function of the average sintered grain-size distribution of alumina. Overall, zirconia grain size seems to influence the average stress, whereas alumina grain size determines the stress distribution.