Straightforward Solvent‐Free Synthesis of Tertiary Phosphine Chalcogenides from Secondary Phosphines,Electron‐Rich Alkenes,and Elemental Sulfur or Selenium

A series of tertiary phosphine sulfides and selenides have been synthesized in excellent yields (88‐99%) via a three‐component reaction between secondary phosphines, electron‐rich alkenes (styrene, vinyl chalcogenides), and elemental sulfur or selenium, proceeding under solvent‐free conditions (80‐82°C, 4–44 h). The interaction occurs via initial oxidation of secondary phosphines with elemental sulfur or selenium followed by noncatalyzed anti‐Markovnikov addition of the generated R₂P(E)H (E = S, Se) species to alkenes to afford the corresponding adducts with high chemo‐ and regioselectivity.     

Approximate Group Analysis and Multiple Time Scales Method for the Approximate Boussinesq Equation

This paper is devoted to investigation of the approximate Boussinesq equation by methods of the approximate symmetry analysis of partial differential equations with a small parameter developed by Baikov, Gazizov and Ibragimov. We combine these methods with the method of multiple time scales to extend the domain of definition of approximate group invariant solutions of the approximate Boussinesq equation.     

Coupled experiments and simulations of microstructural damage in wood

In this paper, we explore ways to couple experimental measurements with the numerical simulations of the mechanical properties of wood. For our numerical simulations, we have adopted a lattice approach, where wood fibers or bundles of wood fibers are modeled as discrete structural elements connected by a lattice of spring elements. Element strength and stiffness properties are determined from bulk material properties. Damage is represented by broken lattice elements, which cause both stiffness and strength degradation. The modeling approach was applied to small specimens of spruce subjected to transverse uniaxial tension, and mode I transverse splitting. The model was found to be good at predicting the load-deformation response of both notched and unnotched specimens, including the post-peak softening response. In addition, the damage patterns predicted by the model are consistent with those observed in the experiments.     

Very Stable Two Mega Dalton High-Molecular-Mass Multiprotein Complex from Sea Cucumber Eupentacta fraudatrix

In contrast to many human organs, only the human liver can self-regenerate, to some degree. Some marine echinoderms are convenient objects for studying the processes of regenerations of organs and tissues. For example, sea cucumbers Eupentacta fraudatrix can completely restore within several weeks, the internal organs and the whole body after their division into two or three parts. Therefore, these cucumbers are a very convenient model for studying the general mechanisms of regeneration. However, there is no literature data yet on which biomolecules of these cucumbers can stimulate the regeneration of organs and the whole-body processes. Studying the mechanisms of restoration is very important for modern biology and medicine, since it can help researchers to understand which proteins, enzymes, hormones, or possible complexes can play an essential role in regeneration. This work is the first to analyze the possible content of very stable protein complexes in sea cucumbers Eupentacta fraudatrix. It has been shown that their organisms contain a very stable multiprotein complex of about 2000 kDa. This complex contains 15 proteins with molecular masses (MMs) >10 kDa and 21 small proteins and peptides with MMs 2.0–8.6 kDa. It is effectively destroyed only in the presence of 3.0 M MgCl₂ and, to a lesser extent, 3.0 M NaCl, while the best dissociation occurs in the presence of 8.0 M urea + 0.1 M EDTA. Our data indicate that forming a very stable proteins complex occurs due to the combination of bridges formed by metal ions, electrostatic contacts, and hydrogen bonds.     

Structural and Metabolic Pattern Classification for Detection of Glioblastoma Recurrence and Treatment-Related Effects

Artificial neuronal network (ANN) in classification of glioblastoma multiforme (GBM) recurrence from treatment effects using advanced magnetic resonance imaging techniques was evaluated. In 56 patients with treated GBM, normalised minimal and mean apparent-diffusion coefficient (ADC) values, vessels number on susceptibility-weighted images (SWI) and Cho/Cr ratio were analysed statistically and by ANN. Significant correlation exists between normalised minimal and mean ADC values, and no correlation between ADC and Cho/Cr values. Cut-off values for tumour presence were: 1.14 for normalised minimal ADC (54% sensitivity, 71% specificity), 1.13 for normalised mean ADC (51% sensitivity, 71% specificity), 1.8 for Cho/Cr ratio (92% sensitivity, 82% specificity), grade 2 for SWI (87% sensitivity, 82% specificity). An accurate prediction of ANN to classify patients into GBM progression or treatment effects group was 99% during the training and 96.8% during the testing phase. Multi-parametric ANN allows distinction between GBM recurrence and treatment effects, and can be used in clinical practice.     

Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence,T1- and ParaCEST MRI

Applying a single molecular probe to monitor enzymatic activities in multiple, complementary imaging modalities is highly desirable to ascertain detection and to avoid the complexity associated with the use of agents of different chemical entities. We demonstrate here the versatility of lanthanide (Ln³⁺) complexes with respect to their optical and magnetic properties and their potential for enzymatic detection in NIR luminescence, CEST and T1 MR imaging, controlled by the nature of the Ln³⁺ ion, while using a unique chelator. Based on X-ray structural, photophysical, and solution NMR investigations of a family of Ln³⁺ DO3A-pyridine model complexes, we could rationalize the luminescence (Eu³⁺, Yb³⁺), CEST (Yb³⁺) and relaxation (Gd³⁺) properties and their variations between carbamate and amine derivatives. This allowed the design of $$ probes which undergo enzyme-mediated changes detectable in NIR luminescence, CEST and T1-weighted MRI, respectively governed by variations in their absorption energy, in their exchanging proton pool and in their size, thus relaxation efficacy. We demonstrate that these properties can be exploited for the visualization of β-galactosidase activity in phantom samples by different imaging modalities: NIR optical imaging, CEST and T1-weighted MRI.     

Strikingly High Activity of 15-Lipoxygenase Towards Di-Polyunsaturated Arachidonoyl/Adrenoyl-Phosphatidylethanolamines Generates Peroxidation Signals of Ferroptotic Cell Death

The vast majority of membrane phospholipids (PLs) include two asymmetrically positioned fatty acyls: oxidizable polyunsaturated fatty acids (PUFA) attached predominantly at the sn2 position, and non-oxidizable saturated/monounsaturated acids (SFA/MUFA) localized at the sn1 position. The peroxidation of PUFA-PLs, particularly sn2-arachidonoyl(AA)- and sn2-adrenoyl(AdA)-containing phosphatidylethanolamines (PE), has been associated with the execution of ferroptosis, a program of regulated cell death. There is a minor subpopulation (≈1–2 mol %) of doubly PUFA-acylated phospholipids (di-PUFA-PLs) whose role in ferroptosis remains enigmatic. Here we report that 15-lipoxygenase (15LOX) exhibits unexpectedly high pro-ferroptotic peroxidation activity towards di-PUFA-PEs. We revealed that peroxidation of several molecular species of di-PUFA-PEs occurred early in ferroptosis. Ferrostatin-1, a typical ferroptosis inhibitor, effectively prevented peroxidation of di-PUFA-PEs. Furthermore, co-incubation of cells with di-AA-PE and 15LOX produced PUFA-PE peroxidation and induced ferroptotic death. The decreased contents of di-PUFA-PEs in ACSL4 KO A375 cells was associated with lower levels of di-PUFA-PE peroxidation and enhanced resistance to ferroptosis. Thus, di-PUFA-PE species are newly identified phospholipid peroxidation substrates and regulators of ferroptosis, representing a promising therapeutic target for many diseases related to ferroptotic death.     

Immobilized enzymes and cells in poly(N-vinyl caprolactam)-based hydrogels

A one-step mild method for entrapping animal cells and enzymes in macroporous composite poly (N-vinyl caprolactam)-calcium alginate (PVCL-CaAlg) hydrogels is described. Some properties of immobilized enzymes, such as thermal and storage stabilities and stability in water/organic media were investigated. Composite PVCL-CaAlg gels were successfully applied to immobilize a number of proteases, namely, trypsin, α-chymotrypsin, carboxypeptidase B, and thrombin. Thermal stability of the immobilized preparations obtained by entrapment in hydrogel beads allowed us to use them at 65–80†C, while the native enzymes were completely inactivated at 50–55°C. Various applications of enzymes and cells immobilized in beads weredemonstrated. Immobilized trypsin and carboxypeptidase B were applied to prepare human insulin from recombinant proinsulin. The hydrogel beads with entrapped α-chymotrypsin were used in enantioselective hydrolysis of Shiff's base of D,L-phenylalanine ethyl ester (SBPH) in acetonitrile/water medium. Thrombin immobilized in PVCL-based hydrogel films was shown to be a promising compound for wound treatment. To prepare pure preparations of monoclonal antibodies (MAb) several hybridoma cell lines, including hybridoma cell lines producing MAb to interleukin-2, were successfully cultivated in the hydrogel beads.