High-Impact PLA in Compatibilized PLA/PCL Blends: Optimization of Blend Composition and Type and Content of Compatibilizer

In this work, the effectiveness of seven commercial compatibilizers is tested in polylactide (PLA)/poly(ε-caprolactone) (PCL) blends with different compositions to obtain a high-impact PLA. None of the compatibilizers is effective for 90/10 and 80/20 PLA/PCL compositions, as no improvement of the impact strength is observed. For the 70/30 composition, compatibilizers having glycidyl methacrylate (GMA) and acrylate groups in their structure are proved the most effective, as the morphological change towards co-continuity induced by them leads to significant impact strength improvements (of ≈345% and 90% with respect to the neat PLA and the noncompatibilized PLA/PCL 70/30 blend, respectively). The 70/30 PLA/PCL composition, as it shows the best balance of properties, and the best compatibilizer (ElvaloyPTW) are chosen to carry out the optimization of the compatibilizer content. It is found that adding 6 phr to the blend results in highly toughened and ductile blends while maintaining a high modulus and yield strength values. Larger compatibilizer contents lead to even higher impact strength values, but the low-strain mechanical properties are notably reduced. Thus, in this work, a simple and easily scalable method to produce high-impact PLA is shown, as it implies the compounding of three commercially available components without involving any toxic solvents.     

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

Detection and Discrimination of Conspecific Scents by the Anguid Slow-Worm Anguis fragilis

We tested the ability of male slow-worms, Anguis fragilis, a limbless anguid lizard with secretive, semifossorial habits, to detect chemical associated with conspecifics by using a T-maze in the laboratory. Male slow-worms discriminated conspecific male and female scent deposits. Males selected the arm with female scent, suggesting that scent deposits may be used to locate potential mates. Also, male slow-worms did not avoid the chemicals of other males, suggesting that they are not territorial. However, males discriminated their own scent from those of other males, and spent more time exploring the arm with other male scent, which suggests that scent marks may bear information that could be used in future intrasexual social contexts. We conclude that discrimination of conspecifics based on scents may be more widespread than previously expected among lizards inhabiting visually restricted environments.     

Synthesis, biological activity, and ADME properties of novel S-DABOs/N-DABOs as HIV reverse transcriptase inhibitors

Previous studies aimed at exploring the SAR of C2-functionalized S-DABOs demonstrated that the substituent at this position plays a key role in the inhibition of both wild-type RT and drug-resistant enzymes, particularly the K103N mutant form. The introduction of a cyclopropyl group led us to the discovery of a potent inhibitor with picomolar activity against wild-type RT and nanomolar activity against many key mutant forms such as K103N. Despite its excellent antiviral profile, this compound suffers from a suboptimal ADME profile typical of many S-DABO analogues, but it could, however, represent a promising candidate as an anti-HIV microbicide. In the present work, a new series of S-DABO/N-DABO derivatives were synthesized to obtain additional SAR information on the C2-position and in particular to improve ADME properties while maintaining a good activity profile against HIV-1 RT. In vitro ADME properties (PAMPA permeation, water solubility, and metabolic stability) were also experimentally evaluated for the most interesting compounds to obtain a reliable indication of their plasma levels after oral administration.     

Evaluating the In Vitro Metabolism of Docosahexaenoic Acid in Sheep Rumen Fluid

Rumen metabolism (e.g., biohydrogenation) of dietary unsaturated fatty acids (FA) is one of the main reasons why ruminant fats tend to be highly saturated and contain many isomerized FA intermediates. The process by which long-chain (20- to 24-carbon FA) polyunsaturated FA (LC-PUFA) are metabolized by rumen bacteria is not as well understood as that of linoleic or linolenic acids. In order to better understand the fate of LC-PUFA in the rumen several concentrations of docosahexaenoic acid (DHA) were evaluated in in vitro batch incubations ranging from 100 to 1,500 μg per 6 mL of incubation volume using rumen fluid from sheep and incubated for 0, 1, 2, 3, and 6 h. From the results, it was shown that DHA was extensively metabolized at low (100 to 300 μg/6 mL incubation volume), but not at high level of inclusion (800 μg). At 300 μg of DHA most of the depleted DHA was recovered as LC-DHA metabolites within the first 6 h of incubation, and at the lowest levels (100 μg of incubation volume) further metabolism is apparent at 6 h. Using SP-2560 GC columns several LC-DHA metabolites were shown to elute after 24:0 and just past DHA, a region generally free of interfering FA. The present in vitro study would appear to be a useful method to evaluate the production of DHA metabolites in combination with its depletion.     

Flexible oligomeric silicon-containing poly(ether-azomethine)s obtained from epoxide derivatives. Synthesis and characterization

Three new diamines derived from epoxide compounds were synthesized. The preparation of diamine monomers implied the reaction between a phenoxyalkyloxirane (alkyl: H, methyl, isopropyl) and bisphenol A, obtaining the respective aliphatic diols, which produced the corresponding dinitro derivatives. Finally, these derivatives were reduced by using palladium/carbon activated as catalyst and hydrazine as a hydrogen source. Then, six oligomeric poly(ether-azomethine)s (PEAzMs) were obtained from a polycondensation reaction between the new diamines and bis(4-formylbiphenyl-4-yl)dialkylsilane (alkyl: methyl, phenyl) with 84–93% yields. The structural characterization of the diamines and PEAzMs was performed by elemental analysis, infrared spectroscopy, and nuclear magnetic resonance spectroscopy (¹H, ¹³C, and ²⁹Si). Furthermore, polymers were analyzed by solubility tests, gel permeation chromatography, ultraviolet–visible (UV–vis) spectroscopy, thermogravimetry, and differential scanning calorimetry analysis. The results showed PEAzMs with 2–11 repetitive units, where the design of the monomers allowed to obtain improved solution processability in comparison with previously reported silylated poly(azomethine)s and good thermal stability. Additionally, all samples showed high transparency in the UV–vis region. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48055.     

High temperature tribological characterisation of TiAlSiN coatings produced by cathodic arc evaporation

This study reports on the wear properties at medium-high temperatures of TiAlSiN films deposited by cathodic arc evaporation on hot work steel substrates. The chemical composition and microstructure of the coatings were characterised by glow discharge optical emission spectroscopy, scanning electron microscopy and X-ray diffraction. The mechanical properties, i.e. hardness and elastic modulus were evaluated by nanoindentation, and the adhesion of the coatings was tested by scratch tests. Coatings with stoichiometries of Ti_0.31Al_0.1Si_0.06N_0.53 and Ti_0.23Al_0.12Si_0.09N_0.55 exhibit microstructures consisting of solid solutions of (Ti,Al,Si)N, where Al and Si replace Ti atoms. These films show high hardness and good adhesion strength to the hot work steels. Conversely, coatings with a stoichiometry of Ti_0.09Al_0.34Si_0.02N_0.55 show a wurtzite-like microstructure, low hardness and poor adhesion strength.The wear rates of the coatings were investigated by ball-on-disc experiments at room temperature, 200 °C, 400 °C and 600 °C, using alumina balls as counter surfaces. At room temperature, the films show wear rates of the same order of magnitude of TiN and TiAlN coatings. On the other hand, the wear rates of solid solution (Ti,Al,Si)N coatings measured at 200, and 400 °C are one order of magnitude smaller than those measured at room temperature due to the formation of oxide-containing tribofilms on the wear tracks. At 600 °C the wear rates increase but still keep smaller than those measured at room temperature, although this effect can be influenced by the softening of the steel substrates by over-tempering. EDS analyses revealed that, between 200 °C and 400 °C, the oxidation of the coating occurs only at the contact zone between the film and the counterpart body due to the sliding process.