Cytotoxic Efficacy and Resistance Mechanism of a TRAIL and VEGFA-Peptide Fusion Protein in Colorectal Cancer Models

TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy of a recently developed chimeric AD-O51.4 protein, a TRAIL fused to the VEGFA-originating peptide. We tested AD-O51.4 protein activity against human colorectal cancer (CRC) models and investigated the resistance mechanism in the non-responsive CRC models. The quantitative comparison of apoptotic activity between AD-O51.4 and the native TRAIL in nine human colorectal cancer cell lines revealed dose-dependent toxicity in seven of them; the immunofluorescence-captured receptor abundance correlated with the extent of apoptosis. AD-O51.4 reduced the growth of CRC patient-derived xenografts (PDXs) with good efficacy. Cell lines that acquired AD-O51.4 resistance showed a significant decrease in surface TRAIL receptor expression and apoptosis-related proteins, including Caspase-8, HSP60, and p53. These results demonstrate the effectiveness of AD-O51.4 protein in CRC preclinical models and identify the potential mechanism underlying acquired resistance. Progression of AD-O51.4 to clinical trials is expected.     

Purification and characterization of three commercial phenylazoaniline disperse dyes

Although tons of disperse dyes are used worldwile, little information on their ecotoxicity is available. While in silico models can be used to predict their ecotoxicity, experimental results from Daphnia can show significantly higher toxicity than predicted. Thus the objective of this work was to extend the knowledge base in this area by evaluating the ecotoxicity of three widely used disperse dyes and comparing the results to predicted values. Bearing in mind that generating ecotoxicity data on azo disperse dyes is complicated because they are not readily found as homogeneous compounds, we employed chromatographic methods to purify three commercially dyes C.I. Disperse Violet 93, Blue 291, and Blue 373 already found in the aquatic environment. No acute toxicity was observed for Daphnia similis. These results seems to be in general agreement when compared with ECOSAR predicted values. We hypothesize that differences in Kow values could explain the variations in results.     

Enhancement of oxygen reduction by incorporation of heteropolytungstate into the electrocatalytic ink of carbon supported platinum nanoparticles

Nafion stabilized inks of Vulcan XC-72 supported platinum (20 wt.%) nanoparticles (Pt/XC-72) were utilized to produce electrocatalytic films on glassy carbon. The catalysts were modified (activated) with phosphododecatungstic acid H₃PW₁₂O₄₀ (PW₁₂). Comparison was made to bare (PW₁₂-free) electrocatalytic films. Electroreduction of dioxygen was studied at 25 °C in 0.5 mol dm⁻³ H₂SO₄ electrolyte using rotating disk voltammetry. For the same loading of platinum (≈95 μg cm⁻²) and for the approximately identical distribution of the catalyst, the reduction of oxygen at a glassy carbon electrode modified with the ink containing PW₁₂ proceeded at ca. 30-60 mV more positive potential (depending on the PW₁₂ content), and the system was characterized by a higher kinetic parameter (rate of heterogeneous electron transfer), when compared to the PW₁₂-free electrocatalyst. Gas diffusion electrodes with Pt/XC-72 supported on carbon paper (Pt loading 1 mg cm⁻²) were also tested. Under the same experimental conditions, while the exchange current density and the total resistance contribution to polarization components, computed from the galvanostatic polarization curves were found to be clearly higher and lower, respectively, for the ink modified with PW₁₂ relative to the unmodified system. The results demonstrate that addition of heteropolytungstatic acid (together with Nafion) enhances the electrocatalytic activity of platinum towards reduction of oxygen.     

Ultrafine-Grained Plates of Al-Mg-Si Alloy Obtained by Incremental Equal Channel Angular Pressing: Microstructure and Mechanical Properties

In this study, an Al-Mg-Si alloy was processed using via incremental equal channel angular pressing (I-ECAP) in order to obtain homogenous, ultrafine-grained plates with low anisotropy of the mechanical properties. This was the first attempt to process an Al-Mg-Si alloy using this technique. Samples in the form of 3 mm-thick square plates were subjected to I-ECAP with the 90 deg rotation around the axis normal to the surface of the plate between passes. Samples were investigated first in their initial state, then after a single pass of I-ECAP, and finally after four such passes. Analyses of the microstructure and mechanical properties demonstrated that the I-ECAP method can be successfully applied in Al-Mg-Si alloys. The average grain size decreased from 15 to 19 µm in the initial state to below 1 µm after four I-ECAP passes. The fraction of high-angle grain boundaries in the sample subjected to four I-ECAP passes lay within 53 to 57 pct depending on the examined plane. The mechanism of grain refinement in Al-Mg-Si alloy was found to be distinctly different from that in pure aluminum with the grain rotation being more prominent than the grain subdivision, which was attributed to lower stacking fault energy and the reduced mobility of dislocations in the alloy. The ultimate tensile strength increased more than twice, whereas the yield strength was more than threefold. Additionally, the plates processed by I-ECAP exhibited low anisotropy of mechanical properties (in plane and across the thickness) in comparison to other SPD processing methods, which makes them attractive for further processing and applications.

     

Photoinitiated polymerization in ionic liquids: Kinetics and viscosity effects

The photo-induced polymerization of poly(ethylene glycol) dimethacrylate and poly(ethylene glycol) monomethacrylate (crosslinking and linear, resp.) in four imidazolium-based ionic liquids (ILs) containing the same cation or the same anion in pairs is reported. The kinetic studies were accompanied by detailed viscosity measurements, which showed the occurrence of an interesting phenomenon - a viscosity synergism in monomer/IL mixtures (i.e. the viscosity of the mixture is higher than the simple additive combination of viscosities of the two components). Viscosity synergism, very important for kinetic considerations, is especially strong for ILs of low viscosity and its magnitude depends on the monomer structure. The polymerization conducted in ILs was considerably faster than in a reference solvent. The propagation rate coefficients were influenced mainly by the anion structure whereas the termination rate coefficients by viscosity of the initial monomer/IL mixture (taking into account the synergistic effect). FTIR studies showed the existence of specific interactions between the carbonyl group in the monomer and C₂-H of the imidazolium ring; the polymerization rates were directly related to the magnitude of the monomer/IL interaction.     

Photochemical Degradation of Disazo Dyes,R-Salt Derivatives,on Dyed Cotton

Direct disazo dyes, R-salt derivatives, were synthesized and examined. The dyes were prepared by coupling of appropriate components with tetrazotized diacyl derivatives of aromatic diamines. Derivatives of dicarboxylic acids with the general formula HOOC―(CH₂)_n―COOH (n = 0 ÷ 4) were used as acylating agents. Photochemical degradation rates of dyes on dyed cotton fabric were studied. Compositions of azo-hydrazone tautomers, their aggregates, and their decay rates in UV-Vis light were determined. It was assumed that the length of aliphatic chain in the molecule affects the rate of its photochemical degradation T_1/2, tautomeric composition, and dyes aggregation in azo and hydrazo forms.     

Microstructural changes upon annealing in ODS-strengthened ultrafine grained ferritic steel

In this study, the stability of grain size and oxide nanoparticles in the ODS steel upon annealing at high temperature (650–1350 °C) has been evaluated. The ODS Fe–Cr–W–Ti–Y₂O₃ steel has been manufactured by powder metallurgy, consolidated by hot isostatic pressing and processed by hydrostatic extrusion. Such a processing brings about ultrafine grain structure reinforced with oxide nanoparticles (few nm in diameter) and results in superior mechanical properties. The stability of nano-oxides has been analyzed by small angle X-ray scattering together with transmission electron microscopy. The results obtained revealed excellent thermal stability of ultrafine grained ODS ferritic steel, which was attributed to the resistance of oxides against coarsening.