Mechanism for the Formation of a Solid Solution of Carbon in Silicon Carbide

We consider a mechanism for the formation of a solid solution of carbon in silicon carbide when various carbide synthesis methods are used that involve participation of thermally expanded (exfoliated) graphite. We have determined the role of chemical transport reactions in processes of solid-phase interaction between the components of the synthesis. We have optimized the conditions for synthesis of a powder of a solid solution of carbon in silicon carbide with participation of thermally expanded graphite.     

LC–MS analysis of the cis isomers of chlorogenic acids

The behaviour of cis isomers of selected mono- and di-acyl chlorogenic acids produced by UV-irradiation has been investigated by LC–MSⁿ. cis Isomers fragment identically to the more common trans isomers. cis-5-Acyl chlorogenic acids are more hydrophobic and elute later than their mono- or di-trans counterparts whereas the reverse is true for cis-3-acyl and cis-4-acyl chlorogenic acids. The cis isomers of 1,3-dicaffeoylquinic acid, the only 1-acyl chlorogenic acid investigated, are also more hydrophobic than the di-trans isomer. Coffee leaves had a proportionately greater content of cis isomers relative to trans isomers compared with coffee beans suggesting that UV-irradiation in vivo may also cause geometric isomerisation.     

Stability and Heat Resistance of Silicide Coatings on Refractory Metals. Part 2. Stability and Heat Resistance of Silicide Coatings on Tungsten and Molybdenum at 1500-2000°C

The kinetics of diffusion redistribution of phases within the system WSi₂ W on heating tungsten silicide in air in the temperature range 1500-2000°C is studied. The stability and heat resistance of silicide coatings on tungsten is mainly governed by the diffusion of silicon towards the interphase boundaries W W₅Si₃, W₅Si₃ WSi₂, and WSi₂ SiO₂, formation at them of diffusion barriers of lower silicide W₅Si₃, and also a protective SiO₂ film at the outer boundary of the silicide coating. It is established that the transition rate for the higher to the lower tungsten silicide WSi₂ W₅Si₃ is on average four times slower than the transition rate for MoSi₂ Mo₅Si₃. It is shown that an increase in silicon concentration in the WSi₂ surface layer stimulates formation of diffusion barrier compounds at interphase boundaries. This leads to an increase in the stability of the phase composition and heat resistance of a silicide coating on metals. In particular at 1700°C the transition rate for molybdenum silicide on tungsten MoSi₂ (Mo, W)₅Si₃ is about twenty times slower than the transition rate for MoSi₂ Mo₅Si₃, and less by a factor of about eleven than the transition rate for WSi₂ W₅Si₃. Here there is also an increase in the heat resistance of silicide coatings on tungsten and molybdenum. It is shown that the SiO₂ film on tungsten silicide does not lose its protective properties up to 2000°C.     

Resveratrol Affects Sphingolipid Metabolism in A549 Lung Adenocarcinoma Cells

Resveratrol is a naturally occurring polyphenol which has various beneficial effects, such as anti-inflammatory, anti-tumor, anti-aging, antioxidant, and neuroprotective effects, among others. The anti-cancer activity of resveratrol has been related to alterations in sphingolipid metabolism. We analyzed the effect of resveratrol on the enzymes responsible for accumulation of the two sphingolipids with highest functional activity—apoptosis promoting ceramide (CER) and proliferation-stimulating sphingosine-1-phosphate (S1P)—in human lung adenocarcinoma A549 cells. Resveratrol treatment induced an increase in CER and sphingosine (SPH) and a decrease in sphingomyelin (SM) and S1P. Our results showed that the most common mode of CER accumulation, through sphingomyelinase-induced hydrolysis of SM, was not responsible for a CER increase despite the reduction in SM in A549 plasma membranes. However, both the activity and the expression of CER synthase 6 were upregulated in resveratrol-treated cells, implying that CER was accumulated as a result of stimulated de novo synthesis. Furthermore, the enzyme responsible for CER hydrolysis, alkaline ceramidase, was not altered, suggesting that it was not related to changes in the CER level. The enzyme maintaining the balance between apoptosis and proliferation, sphingosine kinase 1 (SK1), was downregulated, and its expression was reduced, resulting in a decrease in S1P levels in resveratrol-treated lung adenocarcinoma cells. In addition, incubation of resveratrol-treated A549 cells with the SK1 inhibitors DMS and fingolimod additionally downregulated SK1 without affecting its expression. The present studies provide information concerning the biochemical processes underlying the influence of resveratrol on sphingolipid metabolism in A549 lung cancer cells and reveal possibilities for combined use of polyphenols with specific anti-proliferative agents that could serve as the basis for the development of complex therapeutic strategies.     

Unusual Cytochrome c552 from Thioalkalivibrio paradoxus: Solution NMR Structure and Interaction with Thiocyanate Dehydrogenase

The search of a putative physiological electron acceptor for thiocyanate dehydrogenase (TcDH) newly discovered in the thiocyanate-oxidizing bacteria Thioalkalivibrio paradoxus revealed an unusually large, single-heme cytochrome c (CytC552), which was co-purified with TcDH from the periplasm. Recombinant CytC552, produced in Escherichia coli as a mature protein without a signal peptide, has spectral properties similar to the endogenous protein and serves as an in vitro electron acceptor in the TcDH-catalyzed reaction. The CytC552 structure determined by NMR spectroscopy reveals significant differences compared to those of the typical class I bacterial cytochromes c: a high solvent accessible surface area for the heme group and so-called “intrinsically disordered” nature of the histidine-rich N- and C-terminal regions. Comparison of the signal splitting in the heteronuclear NMR spectra of oxidized, reduced, and TcDH-bound CytC552 reveals the heme axial methionine fluxionality. The TcDH binding site on the CytC552 surface was mapped using NMR chemical shift perturbations. Putative TcDH-CytC552 complexes were reconstructed by the information-driven docking approach and used for the analysis of effective electron transfer pathways. The best pathway includes the electron hopping through His528 and Tyr164 of TcDH, and His83 of CytC552 to the heme group in accordance with pH-dependence of TcDH activity with CytC552.     

Analysis of Circulating Tumor and Cancer Stem Cells Provides New Opportunities in Diagnosis and Treatment of Small Cell Lung Cancer

Current methods for diagnosis and treatment of small cell lung cancer (SCLC) have only a modest efficacy. In this pilot study, we analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with SCLC to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. In other forms of lung cancer, we showed a heterogeneity of blood CTCs and CSCs populations, as well as changes in other cell populations (ALDH⁺, CD87⁺CD276⁺, and EGF⁺Axl⁺) in smokers. A number of CTCs and CSCs in patients with SCLC have been shown to be resistant to chemotherapy (CT). High cytotoxic activity and resistance to apoptosis of reprogrammed CD3⁺CD8⁺ T-lymphocytes (rTcells) in relation to naive CD3⁺CD8⁺ T-lymphocytes was demonstrated in a smoking patient with SCLC (Patient G) in vitro. The target for rTcells was patient G’s blood CSCs. Reprogramming of CD3⁺CD8⁺ T-lymphocytes was carried out with the MEK1/2 inhibitor and PD-1/PD-L1 pathway blocker nivolumab. The training procedure was performed with a suspension of dead CTCs and CSCs obtained from patient’s G blood. The presented data show a new avenue for personalized SCLC diagnosis and targeted improvement of chemotherapy based on the use of both CTCs and CSCs.     

Selective and Reversible 1,3-Dipolar Cycloaddition of 2-(2-Oxoindoline-3-ylidene)acetates with Nitrones in the Synthesis of Functionalized Spiroisoxazolidines

The 1,3-dipolar cycloaddition of 2-(2-oxoindoline-3-ylidene)acetates with functionalized aldo- and ketonitrones proceeds with good selectivity to provide new highly functionalized 5-spiroisoxazolidines. A characteristic feature of these reactions is reversibility that allows for the control of the diastereoselectivity of cycloaddition. The reduction of obtained adducts using zinc powder in acetic acid leads to 1,3-aminoalcohols or spirolactones. For a number of the spiro compounds obtained, anticancer activity was found.