Structural analysis and biomedical potential of novel salicyloyloxy estrane derivatives synthesized by microwave irradiation

New estrane salicyloyloxy or D-homo derivatives were synthesized under microwave (MW) or conventional heating from estrane precursors and methyl salicylate. The MW technique provides advantages regarding product yield and reaction time, and represents a more environmentally friendly approach than conventional heating. Considering the biomedical potential of estrane compounds, we evaluated the antioxidant activity and cytotoxicity of synthesized estrane derivatives in a series of in vitro tests, as well as their 3β-hydroxysteroid dehydrogenase/Δ⁵ → Δ⁴ isomerase (3βHSD) and 17β-hydroxysteroid dehydrogenase types 1, 2 and 3 (17βHSD1, 17βHSD2 and 17βHSD3) inhibition potentials. In DPPH tests, 3-methoxyestra-1,3,5(10)-trien-17β-yl salicylate displayed antioxidant potential, while all compounds exhibited OH radical neutralization activity. 3-Oxoestr-4-en-17β-yl salicylate showed strong cytotoxicity against MDA-MB-231 breast cancer cells, while 17-oxoestra-1,3,5(10)-trien-3-yl salicylate, estra-1,3,5(10)-triene-3,17β-diyl 3-benzoate 17-salicylate and 3-benzyloxy-17-salicyloyloxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile showed the strongest inhibition of PC-3 prostate cancer cell growth. 3-Hydroxyestra-1,3,5(10)-trien-17β-yl salicylate was the best inhibitor of 17βHSD2, suggesting potential use in treating pathological conditions associated with estrogen depletion. For 3-methoxyestra-1,3,5(10)-trien-17β-yl salicylate and 3-oxoestr-4-en-17β-yl salicylate, X-ray crystal structure analysis and molecular energy optimization were performed to define their conformations and energy minima. Very good overlap in the region of the steroidal nucleus was observed for the molecular structures of each analyzed molecule in the crystalline state and after energy optimization, while conformer analysis indicates conformational flexibility in the form of rotation around the C17···O2 bond. Structural geometry analysis for these compounds shows that the region of ring A in steroids, and especially the C3 atom functional group, is important structural features concerning antiproliferative activity against MDA-MB-231 cells.

     

In vitro biological performances of phosphorylcholine-grafted ePTFE prostheses through RFGD plasma techniques

Arterial prostheses made of microporous Teflon (ePTFE) are currently used in vascular surgery as bypasses for small and medium vessels. However, several clinical complications, such as thrombosis, frequently occur in these prostheses when implanted in humans. In this work, an original strategy was developed to improve the hemocompatibility of ePTFE prostheses, based on glow-discharge surface modification followed by chemical grafting of phosphorylcholine, known for its hemocompatible properties. This procedure leads to a covalent attachment of the molecules, therefore preventing their removal by shear stress induced by blood flow at the implant wall. The improvement of the blood compatibility properties of the modified ePTFE arterial prostheses have been investigated by in vitro tests such as thromboelastography, neutrophil adsorption, platelet aggregation, and cell cultures. These in vitro tests put in evidence that thrombogenicity index, platelet aggregation, and neutrophil adhesion were decreased by the molecule grafted on the prostheses. Moreover, the cell growth on the surface of the PRC-grafted prostheses was greatly enhanced in comparison to the virgin prosthesis. Based on these results, it could be concluded that PRC grafting on ePTFE prostheses permit to improve in vitro hemocompatibility and biocompatibility in comparison with their virgin counterpart.     

Simul 6: A fast dynamic simulator of electromigration

Simul 6 is a 1D dynamic simulator of electromigration based on the mathematical model of electromigration in free solutions. The model consists of continuity equations for the movement of electrolytes in a separation channel, acid–base equilibria of weak electrolytes, and the electroneutrality condition. It accounts for any number of multivalent electrolytes or ampholytes and provides a complete picture about dynamics of electromigration and diffusion in the separation channel. The equations are solved numerically using software means which allow for parallelization and multithreaded computation. Simul 6 has a user-friendly graphical interface. It is typically used for inspection of system peaks (zones) in electrophoresis, stacking and preconcentrating analytes, optimization of separation conditions, method development in either capillary zone electrophoresis, isotachophoresis, and isoelectric focusing. Simul 6 is the successor of Simul 5, and has been launched as a free software available for download at https://simul6.app/ .     

Haefliger’s codimension-one singular foliations, open books and twisted open books in dimension 3

We consider singular foliations of codimension one on 3-manifolds, in the sense defined by André Haefliger as being ??₁-structures. We prove that under the obvious linear embedding condition, they are ??₁-homotopic to a regular foliation carried by an open book or a twisted open book. The latter concept is introduced for this aim. Our result holds true in every regularity C ^r , r ?? 1. In particular, in dimension 3, this gives a very simple proof of Thurston??s 1976 regularization theorem without using Mather??s homology equivalence.     

A stochastic surrogate model approach applied to calibration of unstable fluid flow experiments

We propose a stochastic approach for calibration of mixing zone lengths in shock tube experiments. The methodology relies on taking into account uncertain initial data propagated through the basic multifluid Euler equations. In this work, the initial interface position is supposed uncertain, modeled by a stochastic process. The size of the mixing zone is then defined as the support of the probability density function of the stochastic process. This time dependent probability density function is estimated with non-intrusive generalized Polynomial Chaos, its support being in this case cheaply evaluated. This methodology relies on the application of an ergodic principle (Wiener, 1938) and generalizes linear perturbations analysis. It is applied in this Note to the calibration of several experimental results.     

Mechanical Enhancement of the Strain-Sensor Response in Dimers of Strongly Coupled Plasmonic Nanoparticles

Due to their particular optical and mechanical properties, plasmomechanical devices have become choice candidates in strain sensing applications. Using numerical simulation, a plasmomechanical system consisting of two gold nanoparticles with different shapes and separated by a small gap, deposited onto a deformable polydimethylsiloxane membrane, is investigated. With the aim of understanding the relationship between the plasmonic behavior of gold nanoparticles and induced mechanical deformations, mechanical extension ranging from 0% to 20% is applied to the polydimethylsiloxane membrane. In a first step, a mechanical calculation based on a hyperelastic model for polydimethylsiloxane shows that the interparticle spacing is enhanced nonlinearly by a percentage greater than the externally applied deformation, depending on the shape and size of the nanoparticles as well as the polydimethylsiloxane membrane thickness. Full optical simulation of the deformed nanosystems demonstrates that the plasmonic resonance wavelength is highly sensitive to the applied displacements and is enhanced compared to a basic approach where the gap deformation is taken as equal to the macroscopic applied deformation. The best figure of merit ($0.022{\%}^{-1}$) is obtained for the disk–rod dimer near the strong coupling regime, larger than the values reported in the literature for localized nanoparticle systems.