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Oxindole-based natural indoles analogues retain the rigidity and size of the original indole ring system whilst introducing more 3-dimensionality and potential increased water solubility. We report the first preparation of a diverse series of new melatonin analogues 4, 6, 11, 12 based on 3-hydroxy-2-oxindoles (11) and hydroxy-free 2-oxindoles (4, 6, 12) and evaluated their ability to reduce intraocular pressure as well as their neuroprotective and antioxidant properties. Reductive amination was used to obtain new 5-(benzylamino)-substituted (indolin-3-yl)acetonitriles 11 and (indolin-3-yl)acetic acids 12 with high yields. Compounds 4 a, c, 6 a and 11 a, d, h, j-l demonstrated IOP reduction effect in range 15-27 % similar to the effect of reference compounds melatonin and timolol (12 % and 18 % reduction, respectively). 5-(Benzylamino)-substituted 3-hydroxy-2-oxindoles 11, unlike compounds 4, 6, inhibited lipid peroxidation in range 2.075-13.012 μM. Inhibition of NQO2 associated with antioxidant properties of melatonin was also evaluated for synthesized compounds and it was found that compound 11 h showed the best NQO2 inhibitory activity with an IC 50 =39 μM (vs. melatonin IC 50 =64 μM). All synthesized compounds 4, 6, 11, 12 at a concentration of 30 μM do not possess the mitochondrial toxicity. Moreover, no disruption of tubulin polymerization was observed even in the presence of 100 μM of the compounds. Thus, 3-hydroxy-2-oxindole derivatives 11 can be used for drug design of first-in-class antiglaucoma drugs with antioxidant and neuroprotective properties., (© 2025 Wiley-VCH GmbH.)

We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds 1-3) on the development of oxygen-induced retinopathy in newborn rats during a 21-day experiment. It was demonstrated that melatonin and its analogues 1-3 effectively reduce the total protein concentration in the vitreous body of rat pups, decrease concentration of VEGF-A, and lower the level of oxidative stress (as indicated by normalization of antioxidant activity in the vitreous body). Melatonin and its analogues 1-3 equally normalize the level of VEGF-A. Analogues 1 and 2 even exceed melatonin in their ability to reduce protein influx into the vitreous body. However, analogue 2 had no effect on antioxidant activity, while analogues 1 and 3 caused a significant increase in this parameter, with analogue 3 even slightly exceeding melatonin. Thus, it can be concluded that analogues 1-3 are comparable to melatonin and can be utilized as potential therapeutic agents for the treatment of retinopathy of prematurity., (© 2024 John Wiley & Sons Ltd.)

Compounds with a 2-oxindole scaffold play an important role in organic synthesis and especially in the synthesis of bioactive organic compounds, therefore, the development of new methods for modifying this scaffold is a very interesting and urgent task. In the framework of this study, we have created a rational approach to the synthesis of 5-amino-substituted derivatives of 2-oxindole. The approach is characterized by good total yield and a small number of steps. One-stage modification of obtained 5-amino-2-oxindoles leads to compounds with promising antiglaucomic activity. The most active compound 7a reduce intraocular pressure by 24% in normotensive rabbits (18% for reference drug timolol)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids. Various 3-hydroxy-2-oxindoles were synthesized using MW activation for 5-10 min with high yields (up to 98%). The influence of novel compounds applied in instillations on IOP was studied in vivo on normotensive rabbits. The lead compound was found to reduce the IOP by 5.6 Torr (ΔIOP for the widely used antiglaucomatousic drug timolol 3.5 Torr and for melatonin 2.7 Torr).

2,3-Dihydroindoles are promising agents for the synthesis of new compounds with neuroprotective and antioxidant properties. Usually, these compounds are obtained by direct reduction of the corresponding indoles containing acceptor groups in the indole ring for its activation. In this work, we propose a synthetic strategy to obtain new 2,3-dihydroindole derivatives from the corresponding polyfunctional 2-oxindoles. Three methods were proposed for reduction of functional groups in the 2-oxindole and 2-chloroindole molecules using various boron hydrides. The possibility of chemoselective reduction of the nitrile group in the presence of an amide was shown. The proposed synthetic strategy can be used, for example, for the synthesis of new analogs of the endogenous hormone melatonin and other compounds with neuroprotective properties.

Background: Cold and frost are two serious factors limiting the yield of many crops worldwide, including the tea plant (Camellia sinensis (L.) Kuntze). The acclimatization of tea plant from tropical to temperate climate regions resulted in unique germplasm in the North-Western Caucasus with extremely frost-tolerant genotypes., Methods: The aim of the current research was to evaluate the physiological, biochemical and genetic responses of tolerant and sensitive tea cultivars exposed to cold (0 to +2 °C for 7 days) and frost (-6 to -8 °C for 5 days). Relative water content, cell membranes integrity, pH of the cell sap, water soluble protein, cations, sugars, amino acids were measured under cold and frost. Comparative expression of the following genes ICE1, CBF1, WRKY2, DHN1, DHN2, DHN3, NAC17, NAC26, NAC30, SnRK1.1, SnRK1.2, SnRK1.3, bHLH7, bHLH43, P5CS, LOX1, LOX6, LOX7 were analyzed., Results: We found elevated protein (by 3-4 times) and cations (potassium, calcium and magnesium) contents in the leaves of both cultivars under cold and frost treatments. Meanwhile, Leu, Met, Val, Thr, Ser were increased under cold and frost, however tolerant cv. Gruzinskii7 showed earlier accumulation of these amino acids. Out of 18 studied genes, 11 were expressed at greater level in the frost- tolerant cultivar comparing with frost-sensitive one : ICE1, CBF1, WRKY2, DHN2, NAC17, NAC26, SnRK1.1, SnRK1.3, bHLH43, P5CS and LOX6 . Positive correlations between certain amino acids namely, Met, Thr, Leu and Ser and studied genes were found. Taken together, the revealed cold responses in Caucasian tea cultivars help better understanding of tea tolerance to low temperature stress and role of revealed metabolites need to be further evaluated in different tea genotypes., Competing Interests: Yuriy L. Orlov is an Academic Editor for PeerJ., (©2020 Samarina et al.)

Glycogen synthase kinase 3β (GSK-3β) is a widely investigated molecular target for numerous diseases including Alzheimer's disease, cancer, and diabetes mellitus. Inhibition of GSK-3β activity has become an attractive approach for treatment of diabetes and cancer. We report the discovery of novel GSK-3β inhibitors of 3-arylidene-2-oxindole scaffold with promising activity. The most potent compound 3a inhibits GSK-3β with IC 50 4.19 nM. In a cell-based assay 3a shows no significant leucocyte toxicity at 10 µM and is moderately cytotoxic against A549 cells. Compound 3a demonstrated high antidiabetic efficacy in obese streptozotocin-treated rats improving glucose tolerance at a dose of 50 mg/kg body weight thus representing an interesting lead for further optimization., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

C3 is an acute phase protein, and thus its plasma concentration increases quickly and drastically during the onset of inflammation. Insulin plays a complex role in inflammation. Elevated level of plasma C3 was shown to correlate with heightened fasting insulin levels and insulin resistance and appears to be a risk factor for the cardiovascular disease and atherosclerosis. The main source of plasma C3 is liver. Nothing is known about effects of insulin on C3 gene expression and protein secretion by hepatocytes. In light of these data we asked if insulin is capable of regulating C3 production in hepatocytes. Here we show that insulin downregulates C3 gene expression in human hepatoma cells HepG2 through activation of PI3K, mTORC1, p38 and MEK1/2 signaling pathways. Transcription factors PPARα, PPARγ, HNF4α and NF-κB are important contributors to this process. Insulin activates PPARγ through PI3K/Akt/mTORC1 pathway, which results in PPARγ binding to DR4 and DR0 cis-acting elements within the C3 promoter and subsequent displacement of HNF4α and PPARα from these sites. As a result PPARα/NF-κB complex, which exists on C3 promoter, is broken down and C3 gene expression is downregulated. The data obtained can potentially be used to explain the molecular mechanism underlying the correlation between heightened level of plasma C3 and insulin resistance in humans., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The creation of gas chromatography is traditionally associated with the names of Nobel Prize winner Archer Martin and his colleagues Richard Synge and Anthony James. However, sometimes references to their predecessors can be found. An investigation conducted by the authors of this article not only confirmed the reliability of these references; but in fact led to the conclusion that by 1952, which is commonly believed to be the year when gas chromatography was born, many research papers had already been devoted to this method, mainly, in its gas-solid version. These papers are considered in this article., (Copyright © 2018. Published by Elsevier B.V.)

A high-power ultrawideband radiation source has been developed which is capable of synthesizing electromagnetic pulses with different frequency bands in free space. To this end, a new circuit design comprising a four-channel former of bipolar pulses of durations 2 and 3 ns has been elaborated and conditions for the stable operation of gas gaps of independent channels without external control pulses have been determined. Each element of the 2 × 2 array of combined antennas is driven from an individual channel of the pulse former. Antennas excited by pulses of the same duration are arranged diagonally. Two radiation synthesis modes have been examined: one aimed to attain ultimate field strength and the other aimed to attain an ultimate width of the radiation spectrum. The modes were changed by changing the time delay between the 2-ns and 3-ns pulses. For the first mode, radiation pulses with a frequency band of 0.2-0.8 GHz and an effective potential of 500 kV have been obtained. The synthesized radiation pulses produced in the second mode had an extended frequency band (0.1-1 GHz) and an effective potential of 220 kV. The pulse repetition frequency was 100 Hz.

Apolipoprotein A-I (ApoA-I) is a key component of high density lipoproteins which possess anti-atherosclerotic and anti-inflammatory properties. Insulin is a crucial mediator of the glucose and lipid metabolism that has been implicated in atherosclerotic and inflammatory processes. Important mediators of insulin signaling such as Liver X Receptors (LXRs) and Forkhead Box A2 (FOXA2) are known to regulate apoA-I expression in liver. Forkhead Box O1 (FOXO1) is a well-known target of insulin signaling and a key mediator of oxidative stress response. Low doses of insulin were shown to activate apoA-I expression in human hepatoma HepG2 cells. However, the detailed mechanisms for these processes are still unknown. We studied the possible involvement of FOXO1, FOXA2, LXRα, and LXRβ transcription factors in the insulin-mediated regulation of apoA-I expression. Treatment of HepG2 cells with high doses of insulin (48 h, 100 nM) suppresses apoA-I gene expression. siRNAs against FOXO1, FOXA2, LXRβ, or LXRα abrogated this effect. FOXO1 forms a complex with LXRβ and insulin treatment impairs FOXO1/LXRβ complex binding to hepatic enhancer and triggers its nuclear export. Insulin as well as LXR ligand TO901317 enhance the interaction between FOXA2, LXRα, and hepatic enhancer. These data suggest that high doses of insulin downregulate apoA-I gene expression in HepG2 cells through redistribution of FOXO1/LXRβ complex, FOXA2, and LXRα on hepatic enhancer of apoA-I gene. J. Cell. Biochem. 118: 382-396, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Apolipoprotein A-I (ApoA-I) is the main anti-atherogenic component of human high-density lipoproteins (HDL). ApoA-I gene expression is regulated by several nuclear receptors, which are the sensors for metabolic changes during development of cardiovascular diseases. Activation of nuclear receptor PPARγ has been shown to impact lipid metabolism as well as inflammation. Here, we have shown that synthetic PPARγ agonist GW1929 decreases both ApoA-I mRNA and protein levels in HepG2 cells and the effect of GW1929 on apoA-I gene transcription depends on PPARγ. PPARγ binds to the sites A and C within the hepatic enhancer of apoA-I gene and the negative regulation of apoA-I gene transcription by PPARγ appears to be realized via the site C (-134 to -119). Ligand activation of PPARγ leads to an increase of LXRβ and a decrease of PPARα binding to the apoA-I gene hepatic enhancer in HepG2 cells. GW1929 abolishes the TNFα-mediated decrease of ApoA-I mRNA expression in both HepG2 and Caco-2 cells but does not block TNFα-mediated inhibition of ApoA-I protein secretion by HepG2 cells. These data demonstrate that complex of PPARγ with GW1929 is a negative regulator involved in the control of ApoA-I expression and secretion in human hepatocyte- and enterocyte-like cells. J. Cell. Biochem. 117: 2010-2022, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Here, we describe a source of high-power ultrawideband radiation with elliptical polarization. The source consisting of a monopolar pulse generator, a bipolar pulse former, and a helical antenna placed into a radioparent container may be used in tests for electromagnetic compatibility. In the source, the helical antenna with the number of turns N = 4 is excited with a high-voltage bipolar pulse. Preliminary, we examined helical antennas at a low-voltage source aiming to select an optimal N and to estimate a radiation center position and boundary of a far-field zone. Finally, characteristics of the source in the operating mode at a pulse repetition rate of 100 Hz are presented in the paper as well. Energy efficiency of the antenna is 0.75 at the axial ratio equal to 1.3. The effective potential of radiation of the source at the voltage amplitudes of the bipolar pulse generator equal to -175/+200 kV reaches 280 kV.

Complement C3 is a pivotal component of three cascades of complement activation. The liver is the main source of C3 in circulation and expression and secretion of C3 by hepatocytes is increased during acute inflammation. However, the mechanism of the regulation of the C3 gene in hepatocytes is not well elucidated. We showed that the C3 gene is the direct target for peroxisome proliferator-activated receptor α (PPARα) in human hepatoma HepG2 cells and mouse liver. Using PPARα siRNA and synthetic PPARα agonist WY-14643 and antagonist MK886 we showed that activation of PPARα results in up-regulation of C3 gene expression and protein secretion by HepG2 cells. The PPAR response element (PPRE), which is able to bind PPARα in vitro and in vivo, was found in the human C3 promoter. PPRE is conserved between human and mouse, and WY-14643 stimulates mouse C3 expression in the liver. TNFα increases C3 gene via NF-κB and, to a lesser extent, MEK1/2 signaling pathways, whereas TNFα-mediated stimulation of C3 protein secretion depends on activation of MEK1/2, p38, and JNK in HepG2 cells. Activation of PPARα abolishes TNFα-mediated up-regulation of C3 gene expression and protein secretion due to interference with NF-κB via PPRE-dependent mechanism in HepG2 cells. TNFα decreases PPARα protein content via NF-κB and MEK1/2 signaling pathways and inhibits PPARα binding with the human C3 promoter in HepG2 cells. These results suggest novel mechanism controlling C3 expression in hepatocytes during acute phase inflammation and demonstrate a crosstalk between PPARα and TNFα in the regulation of complement system.

A set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized using solid phase peptide synthesis and chemical ligation technique. Selective chemical ligation was achieved as a result of hydrazone formation in the course of interaction between NLS hydrazide and GnRH analog modified by pyruvic acid. The efficiency of synthesized peptide carriers was demonstrated in experiments with human cancer cells transfected by reporter luciferase and beta-galactosidase genes or suicide HSV-1 thymidine kinase gene. It was shown that selectivity of action on cancer cells can be achieved as a result of peptide/DNA complex penetration through the cell membrane by GnRH receptor-mediated endocytosis pathway.

To improve the efficiency of anticancer drugs due to their delivery to intracellular targets a set of GnRH analogues containing nuclear localization signal (NLS) of SV-40 virus large T-antigen have been synthesized. NLS was attached to the parent molecule via ε-amino group of D-Lysine in position 1 or 6 of peptide sequence using orthogonal protection strategy. The biological activity studies revealed that incorporation of NLS moiety significantly increases cytotoxic activity of palmitoyl-containing GnRH analogues in vitro. The influence of tested peptides on tumor cells does not accompanied by the destruction of cell membrane, as confirmed in experiments with normal fibroblasts, used as a control.

Genetic modification of mammalian embryos is an important way to model various changes in human development; also, it is an instrument for studying the functions of certain genes in mammals. Using our own experience in developing modes of delivery of genetic constructions to mammals in a nonviral way, we present here data on the delivery of a eukaryotic expression vector to mice embryos through the transplacental barrier with the use of hydrodynamic intravenous injections of DNA-hybrid peptide complexes to pregnant females. The peptide has a cationic part for interaction with DNA and includes a ligand structure towards receptors of the releasing factor of luteinizing hormone (RFLH, luliberin). Advantages of the suggested method are simplicity, economy, nonimmunogenicity for females, and the ability to multiply repeat the procedure. On the basis of the method, systemic gene delivery into tissues of mammalian embryos may be developed.

The rate and character of skin tissue regeneration after wounds, burns and other traumas depend on the cell proliferation within damaged area. Acceleration of healing by stimulation of cell proliferation and extracellular matrix synthesis is one of the most important tasks of modern medicine. There are gene therapy approaches to wound treatment consisting in the transfer of genes encoding mitogenic growth factors to wound area. The most important step in the development of gene therapy approaches is the design of gene delivery tools. In spite of high efficacy of viral vectors, the non-viral means have some preferences (low toxicity, low immunogenity, safety and the absence of backside effects). Among non-viral gene delivery tools, molecular conjugates are the most popular because of their efficacy, simplicity, and the capacity to the targeted gene transfer. In the present work we have developed two molecular conjugates--NLS-TSF7 and NLS-TSF12 consisting of the modified signal of nuclear localization of T-antigen of SV40 virus (cationic part) and the peptide ligands of mammalian transferrin receptor (ligand part). These conjugates bind to plasmid DNA with formation of polyelectrolytic complexes and are capable to deliver plasmid DNA into cells expressing transferrin receptors by receptor-mediated endocytosis. Transfer of the expression vector of luciferase gene in the complex with molecular conjugate NLS-TSF7 to murine surface tissues led to about 100 fold increasing of luciferase activity in comparison with the transfer of free expression vector. Treatment of slash wounds in mice with the complexes of expression vector of synthetic human gene encoding insulin-like growth factor 1 with molecular conjugates NLS-TSF7 led to acceleration of healing in comparison with mice treated with free expression vector. The results obtained confirm the high efficiency of the developed regenerative gene therapy approach for the treatment of damaged skin tissues in mammals.

This work was devoted to the study of conditions of the formation of DNA/K8 complex and analysis of factors effecting the entry of DNA/K8 complex into mammalian cells in comparison with DNA complexes with arginine-rich fragment (47-57) of human immunodeficiency virus (type 1) transcription factor Tat (Tat peptide). The stoichiometry of positively charged DNA/K8 complexes has been studied for the first time. Non-cooperative character of DNA-K8 interaction was revealed. It has been shown that along with the positive charge of such complexes, the presence of an excess of free K8 peptide in the culture medium is a necessary condition for maximal efficiency of cell transfection with DNA/K8 complexes. A stimulatory effect of free K8 peptide on the efficiency of mammalian cell transfection by DNA/K8 complexes is likely to be mediated by the interactions of cationic peptide K8 with negatively charged proteoglycans on the cell surface, which leads to protection of DNA/K8 complexes from disruption by cellular heparan sulfates. However, the protective role of free cationic peptides depends not only on their positive charge, but also on the primary structure of the peptide. In contrast with the results obtained for DNA complexes with molecular conjugates based on poly-L-lysine, the aggregation of DNA/K8 complexes leads to a significant increase in the expression of transferred gene.

Human apolipoprotein A-I gene (apoA-I) plasmid expression vectors were transferred into mice by hydrodynamic injections into tail vein. Two types of expression vectors were used. First one -pCMVcapoAI contains cDNA of apo A-I driven by human cytomegalovirus early gene promoter (CMV). Second one--pAlg contains genomic locus of intron-containing apo A-I under control of own extended 5'-regulatory region (APOAI). Hydrodynamic intravenous injections of both expression vectors led to appearance of human apo A-I mRNA in the liver and human Apo A-I protein in the serum of injected mice. Dynamics of human Apo A-I content in the serum of mice injected by pCMVcapoAI and pAlg were different. When pCMVcapoAI was used, maximal concentration of human Apo A-I protein in the mouse serum was detected one day after injection with following decline to zero level during next two weeks. Under the same conditions injections of pAlg led to maximal level of human Apo A-I concentration in the mouse serum (up to 20 mkg/ml in some animals) on the 5th-7th day of experiment with following graduate decline during several months (human Apo A-I concentration in the serum of oldest analyzed mouse (6 months after injection) was about 25% of its maximal level in the same animal). Levels of human Apo A-I concentration in the mouse serum were compatible after injections of both expression vectors, in spite of much more strong activity of CMV promoter in comparison with APOAI in cultured human hepatoma cells HepG2. We ascribe the revealed difference in dynamics of human Apo A-I expression to delay of apo A-I transcription from pAlg vector, that was confirmed by nested RT-PCR. Significant level and long-term persistence of human Apo A-I in the serum of mice injected by pAlg could be explained by properties of APOAI or (and) exon-intron structure of genomic apo A-I gene. To test the role of APOAI in long-term expression of human Apo A-I in the mice we performed hydrodynamic injections of plasmid vectors containing cDNA of reporter gene encoding luciferase driven by variants of APOAI. No long-term expression of luciferase was found in the livers of injected mice. Therefore, our data suggest the role of exon-intron structure in maintaining of efficient and long-term expression of transferred human apo A-I.

An efficient reaction between triphenylphosphine or triphenyl phosphite and 2-oxoindoline-3-ylidene derivatives in the presence of acetylenic esters leads to functionalized 2-oxoindoline-3-ylidene containing phosphorus ylieds or phosphonate esters. All compounds obtained in these reactions are stable and have good yields. [ABSTRACT FROM AUTHOR]

Cordierite ceramic is usually used for diesel particulate filter owing to its excellent low thermal expansion coefficient and high thermal shock resistance properties. However, the co‐exited intermediate spinel phase can deteriorate the thermal and mechanical performances of cordierite ceramic product, because the spinel phase has much higher thermal expansion coefficient comparing to that of cordierite. In this study, two methods are utilized to reduce the spinel impurity in the cordierite ceramic. On the one hand, rational reaction resources were introduced to decrease spinel production. The formation of intermediate spinel phase is systematically researched by X‐ray diffraction (XRD), scanning electron microscopy (SEM), Raman characterizations and the results clarified the preference of path "Enstatite + Mullite → Cordierite" for less spinel production in comparison to path "Enstatite + Al2O3 → Cordierite + Spinel." Additionally, MgO was introduced as fluxing agent to promote liquid‐phase sintering, thus facilitating the conversion of spinel. On the other hand, the sintering schedule was improved by introducing a holding temperature gradient to promote the diffusion of Si4+ and further promote the conversion of spinel into cordierite. With these methods, the residual spinel phase is minimized, the resulting high‐purity cordierite has a 47% reduction in the thermal expansion coefficient from 3.07 × 10−6/K to 1.63 × 10−6/K compared to the original cordierite sample. [ABSTRACT FROM AUTHOR]

Zirconia toughened alumina (ZTA) has a wide range of applications in high temperature. Though some routes were reported to enhance the mechanical properties at room temperature, the preparation of ZTA with improved high temperature properties was still unknown. In this work, cordierite/ZTA pre‐stressed ceramics (marked as Cor‐ZTA30) have been fabricated successfully by using prestressed coating reinforcement method. The relationships among the temperature, residual stress and the flexural strength of Cor‐ZTA30 have been established based on experimental data. Due to the compressive stresses exists in the surface layer of Cor‐ZTA30 hinder the crack extension, the flexural strength of Cor‐ZTA30 was greatly enhanced at the temperatures below 1000°C. In addition, the difference in flexural strength between coated and uncoated ZTA ceramics decreased with increasing temperature until 1000°C. It indicated that the residual stress vanished entirely as the temperature above 1000°C, which resulted in the same flexural strength for ZTA and Cor‐ZTA30. Therefore, strengthening ZTA ceramics by prestressing is available under the temperatures below 1000°C. [ABSTRACT FROM AUTHOR]

The stress–strain behavior of ceramics, such as aluminum titanate, has certain features that are unusual for brittle materials—in particular, a substantial nonlinearity under uniaxial tension, and load–unload hysteresis caused by the sharp increase of the incremental stiffness at the beginning of unloading. These features are observed experimentally and are attributed to microcracking. Here we compare different degrees of stress–strain nonlinearity of aluminum titanate materials and quantitatively model them. We use advanced mechanical testing to observe the mechanical response at room and high temperature; electron microscopy, and X‐ray refraction radiography to observe the microstructural changes. Experiments show that two types of microcracks can be distinguished: (i) microcracks induced by cooling from the sintering temperature (due to heterogeneity and anisotropy of thermal expansion), with typical sizes of the order of grain size, and (ii) much larger microcracks generated by the mechanical loading. The two microcrack types produce different effects on the stress–strain curves. Such microcracks and the features of the stress–strain behavior depend on the density of the cooling‐induced microcracks and on the distribution of grain sizes. They are modeled analytically and numerically. [ABSTRACT FROM AUTHOR]

We consider the main features of detailed dynamics of the bimolecular process of recombination of the atomic ion Cs+ with the ions F– and I– via the ionic complex consisting of the Ar or Xe atom and the Cs+ ion. Recombination was simulated within the framework of the quasiclassical trajectory method on the potential energy surfaces identical to the surfaces used earlier for studying the direct three-body recombination reactions involving the same particles. Eight kinematic parameters of bimolecular recombination are described. Of them, the main parameters are the collision energy and the impact parameter of a collision of the halide ion with the ionic complex. The results of visualization of eight trajectories corresponding to recombination are presented. The central stage of the recombination process (the energy transfer from the ion pair to the neutral atom and its detachment from the cesium ion with the formation of a stable cesium halide molecule) takes a small share of the trajectory length. [ABSTRACT FROM AUTHOR]

A method was developed for the synthesis of selectively labeled [15N]indole, allowing to obtain the target product with high chemical and isotopic purity. One-dimensional and two-dimensional 1H, 13C, and 15N NMR spectra were examined. The chemical shifts of 1H, 13C, and 15N nuclei were determined, as well as the spin-spin coupling constants of 15N nucleus and the isotopic chemical shifts of 13C nuclei for [15N]indole in CD3CN solution, caused by the replacement of 14N nucleus with a 15N nucleus. It was demonstrated that isotopic shifts of this type can provide important structural information. The NMR data set obtained in the current work can serve as an important reference point for establishing the structures of new aromatic heterocycles. [ABSTRACT FROM AUTHOR]

The study of winter stress tolerance in perennial legumes needs to consider the complete symbiotic system including both plants and bacteria since these two partners are differentially affected by stress conditions. Here, we compared the regrowth after a freezing stress of four different associations of two alfalfa populations differing in freezing tolerance (A-TF0 and A-TF7) inoculated with two Sinorhizobium (Ensifer) meliloti strains (B399 and NRG34) of contrasted adaptation to cold. To understand the contribution of each partner to a better regrowth performance of an association after freezing, we identified molecular traits having major roles in cold acclimation, freezing tolerance, and those involved in the crosstalk between alfalfa and its symbiotic partner. Regrowth after exposure to a freezing stress was 35% larger in the A-TF7 × NRG34 than in the A-TF0 × B399 association. The metabolomic study of roots, crowns and, more specifically, nodules, revealed profound changes in these organs, switching from a sink to support cold acclimation to a source of reserves enabling regrowth after deacclimation. Marked increases in concentrations of stachyose and raffinose, two sugars of the raffinose-family oligosaccharides (RFO), and in the expression level of a gene of the RFO synthetic pathway were observed in response to cold acclimation supporting the importance of a protective role for RFO in alfalfa. Both cold-adapted partners of the symbiotic association contributed to increases in arginine concentration in nodules in response to cold acclimation and deacclimation underscoring the importance of N storage and remobilization for a successful overwintering in alfalfa. [ABSTRACT FROM AUTHOR]

The aim of this work is to study the effect of various talc rocks for the preparation of talc-based cordierite ceramics. Raw talc and sintered cordierite-based ceramic samples (1000-1375ºC for 2 h) were characterized using XRD, XRF, TGA-DTG, laser PSDs, Archimedes method, SEM-EDAX and dielectric relaxation spectrometer (DRS). Results show that impurity oxide contents, particle size and mineralogical changes of green batches influenced the microstructure densification and crystallization of orthorhombic and hexagonal cordierite. The complex electric modulus plot shows the existence of two relaxation processes associated with the capacitive contribution grain boundaries and grain at low and high frequencies, respectively. The dielectric loss reached much lower values (0.0004–0.0007) for the ceramics composed of higher cordierite phase composition (87.00 to 92.00wt.%) that sintered at 1350 and 1375ºC. Such ceramics could be promising in electronic applications like capacitors, microwave devices and wireless communication. [ABSTRACT FROM AUTHOR]

ATP-binding cassette transporter A-I (ABCA1) is an ubiquitously expressed protein whose main function is the transmembrane transport of cholesterol and phospholipids. Synthesis of ABCA1 protein in liver is necessary for high-density lipoprotein (HDL) formation in mammals. Thus, the mechanism of ABCA1 gene expression regulation in hepatocytes are of critical importance. Recently, we have found the insulin-dependent downregulation of other key player in the HDL formation—apolipoprotein A-I gene (J. Cell. Biochem., 2017, 118:382-396). Nothing is known about the role of insulin in the regulation of ABCA1 gene. Here we show for the first time that insulin decreases the mRNA and protein levels of ABCA1 in human hepatoma cell line HepG2. PI3K, p38, MEK1/2, JNK and mTORC1 signaling pathways are involved in the insulin-mediated downregulation of human ABCA1 gene. Transcription factors LXRα, LXRβ, FOXO1 and NF-κB are important contributors to this process, while FOXA2 does not regulate ABCA1 gene expression. Insulin causes the decrease in FOXO1, LXRα and LXRβ binding to ABCA1 promoter, which is likely the cause of the decrease in the gene expression. Interestingly, the murine ABCA1 gene seems to be not regulated by insulin in hepatocytes (in vitro and in vivo). We suggest that the reason for this discrepancy is the difference in the 5ʹ-regulatory regions of human and murine ABCA1 genes. [ABSTRACT FROM AUTHOR]

The capability to fabricate ultra-low and customizable CTE materials with good mechanical properties in a simple method was demonstrated in this work. For this purpose, nano beta-eucryptite and alumina powders were synthesized and used in the composite's fabrication. Four composites of alumina and a second-phase beta-eucryptite were prepared, containing 10, 20, 30, and 40 wt.% beta-eucryptite. The temperature effect on prepared composites is investigated. The results of XRD analysis and the microstructures of prepared composites are discussed with results of mechanical strength and thermal expansion at temperature ranges of 1400, 1500, and 1550 °C. The CTE of alumina-beta-eucryptite composites decrease as the beta-eucryptite content increases, reaching -1.036 × 10–6 °C−1. The findings show that a composite with a very low thermal expansion coefficient and good mechanical properties can be designed and used in different applications. [ABSTRACT FROM AUTHOR]

The main goal of the study is to make an optimization algorithm for plasma etch rate of deposited thin films by adaptive neuro fuzzy inference system (ANFIS). ANFIS represent a heuristic optimization method with back propagation training in one direction and gradient descent algorithm in backwards. The experimental training data samples are acquired for published literature. There are operating parameters which have impact on the plasma etch rate. Input attribute source power has the highest influence on the etch rate. Combination of source power and bias power has the highest influence on the etch rate. Combination of source power, bias power, and pressure has the highest influence on the etch rate. The study considering different operating parameters simultaneously is believed to be the first on a small scale and to attract the interest of everyone. [ABSTRACT FROM AUTHOR]

This work evaluates the influence of the interface characteristics on the measurable quantities that reflect the overall response of ceramic composites. The situations that may lead to the misinterpretation of the experimental results are evidenced. The study is carried out on representative volume elements (RVEs) of periodic microstructures with either perfect adhesion or pure frictional coupling between the matrix and the reinforcement. These alternatives may constitute the initial and the final material configuration in the presence of damaging processes. The mechanical response to common characterization tests is reproduced by numerical analyses, and measurable quantities are evaluated by computational homogenization procedures. Different material combinations with fiber or particle inclusions are analyzed. The case of porous composites is also introduced for comparison purposes. Overall stresses and strains are not proportional in the presence of frictional interfaces. It is however shown that the deviation from linearity is slight and prone to be confused with experimental inaccuracies, e.g. due to the initial adjustment of the testing devices. The effect on the effective material proprieties is significant, though. [ABSTRACT FROM AUTHOR]

Following previous study on non-microcracked porous ceramics (SiC and alumina), we studied the micro and macrostrain response of honeycomb porous microcracked ceramics under applied uniaxial compressive stress. Cordierites of different porosities were compared. Both macroscopic and microscopic strains were measured, by extensometry and neutron diffraction, respectively. Lattice strains were determined using a single diffraction peak (steady-state neutron source) in both the axial and the transverse sample directions. Complementarily, we measured the macroscopic Young's modulus of these materials as a function of temperature, at zero load, using high-temperature laser ultrasound spectroscopy. This allowed having a non-microcracked reference state for all the materials investigated. Confirming our previous study, we observed that macrostrain relaxation occurs at constant load, which is not observed in non-microcracked compounds, such as SiC. This relaxation effect increases as a function of porosity. Moreover, we generally observed a linear dependence of the diffraction modulus on porosity. However, for low and very high applied stress, the lattice strain behavior versus stress seems to be influenced by microcracking and shows considerable strain release, as already observed in other porous microcracked ceramics. We extended to microcracked porous ceramics (cordierite) the macro to microstrain and stress relations previously developed for non-microcracked ceramics, making use of the integrity factor (IF) model. Using the whole set of data available, the IF could also be calculated as a function of applied stress. It was confirmed that highly porous microcracked materials have great potential to become stiffer and more connected. [ABSTRACT FROM AUTHOR]

The incidence of colon cancer is amongst the top three in the world. The tumour microenvironment plays an important role in the occurrence and development of colon cancer. Stromal cells and immune cells are the main components of the tumour microenvironment. Our study detected genes, which affected the infiltration of stromal, immune cells and the way they affected the prognosis of colon cancer patients. We found that the colon's immune system had a special way to affect the tumour microenvironment. Moderate infiltration of stromal and immune cells was proved to be important protective factors for colon cancer patients, which has not been found in other tumours. C3, C5, CXCL12, GNAI1, LPAR1, PENK, PYY, SAA1 and SST were the differential expression hub genes of moderate‐stromal and immune score group. They had a more significant correlation with tumour purity and infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophage, neutrophil, democratic cells. The proteins encoded by C3, C5, CXCL12, GNAI1, PENK, PYY, SST were detected in colon cancer cells. These genes had the potential to become markers to predict the prognosis of patients with colon cancer. [ABSTRACT FROM AUTHOR]

The work is devoted to the study of the mechanical properties of porous ceramics based on diatomite, which has high porosity, adsorption capacity, weak thermal and acoustic conductivity, refractoriness and acid resistance. Based on the morphological analysis of the samples, the numerical value of the sample's porosity was determined. The mechanical properties of the samples were determined by static and dynamic loading methods. The values of static and dynamic elastic moduli of the samples were experimentally measured. The research results showed that, for the material under consideration, at the initial stages of compression processes, the processes of elastic deformation are mainly realized with the subsequent transition to the region of plastic deformation. It was also found that for highly porous samples in the elastic deformation region, the manifestation of pressing processes is possible. In this work, the study of the dependence of the dynamic modulus of porous diatomite ceramics on porosity was carried out: a decrease in elastic moduli was recorded with an increase in the material porosity. A decrease in material porosity after deformation is found. [ABSTRACT FROM AUTHOR]

The paper presents the design of a combined antenna, optimized in numerical calculations to radiate high‐power bipolar pulses with a duration of 0.5 ns. According to the results of the calculations, a compact antenna with the dimensions of 60 × 65 × 55 mm3 (width × height × length) was made. The influence of a high‐voltage insulator position relative to the antenna input on the matching band of the antenna with the coaxial feeder is shown. In the absence of an isolator, the matching band is in the range of 0.98–9.33 GHz. The antenna efficiency by the peak electric field strength and the energy efficiency are equal to 0.75–0.8 and 0.9, respectively. [ABSTRACT FROM AUTHOR]

In this work, we performed the comparative study of plasma parameters, steady-state gas phase compositions and Si reactive-ion etching kinetics in CF4 + O2 + Ar, CHF3 + O2 + Ar and C4F8 + O2 + Ar gas mixtures with variable O2/Ar component ratios. It was found that the substitution of Ar for O2 (a) did not disturb the well-known correlation between the polymerizing ability and the F/C ratio in the original fluorocarbon molecule; (b) causes similar changes in electrons- and ions-related plasma parameters (electron temperature, plasma density, ion bombardment energy); and (c) always suppresses densities of polymerizing radicals and reduces the polymer film thickness. At the same time, the specific effects of oxygen on F atom kinetics result in sufficient differences in their densities and fluxes. It was shown that the dominant etching mechanism for Si in all three gas systems is the chemical etching pathway provided by F atoms (since the contribution of physical sputtering is below 10%) while measured etching rates do not follow the behavior of F atom flux. The phenomenological analysis of heterogeneous process kinetics allowed one to suggest factors influencing the effective reaction probability. These are either the transport of F atoms through thick polymer film (in the case of high-polymerizing C4F8 + O2 + Ar plasma) or heterogeneous reactions with a participation of oxygen atoms under the condition of thin or non-continuous polymer film (in the case of low-polymerizing CF4 + O2 + Ar plasma). [ABSTRACT FROM AUTHOR]

Fouling is one of the drawbacks in membrane filtration systems, reducing the water quality and decreasing the lifespan of a membrane filtration system. In this study, we propose a surface modification on polyethersulfone (PES) membrane by using plasma polymerization with heptylamine as the precursor by varying the deposition time from 3 to 15 min to induce hydrophilic surface of the membrane without changing the bulk properties of PES membrane. Cross-flow filtration and water contact angle of the PES membrane were used to measure permeate flux and Congo red rejection. Based on permeate flux, we calculate the fouling tendencies of each membrane and the result showed that sample with 5-min deposition time produces the best permeate flux (58% increase) and the lowest fouling tendencies (65% decrease) when compared to the untreated membrane. From the EDX mapping, the deposition enables to introduce a stable nitrogen element into the membrane with the homogeneous distribution. This plasma-based post-surface modification demonstrates the encouraging potential to improve significantly the permeate flux, rejection and fouling properties compared to the untreated commercial filtration membrane. [ABSTRACT FROM AUTHOR]

Glycogen synthase kinase-3β (GSK-3β) is a highly conserved multifunctional serine/threonine (Ser/Thr) protein kinase widely expressed in many tissues. GSK-3β inhibitors could be used in the treatment of human key diseases, such as cancer, Alzheimer's disease, Parkinson's disease, inflammation, type-II diabetes, and so on, due to the multi-role of GSK-3β in the hepatic glycolysis regulation, cell signaling pathways, and phosphorylation of various proteins. Recently, sets of diverse GSK-3β inhibitors have been prepared, and biologically evaluated in vitro and in vivo in different screening models. This review summarizes the latest developments in GSK-3β inhibitors unclosed from 2015 to 2019, including their structure–activity relationship and bioactivity studies. [ABSTRACT FROM AUTHOR]

The investigation of etching kinetics and surface conditions for KNbxOy thin films in CF4 + Ar and Cl2 + Ar inductively coupled plasmas was carried out. The variable processing parameters were Ar content in a feed gas (0–75% Ar), gas pressure (4–10 mTorr) and input power (400–700 W) at constant bias power of 100 W. The combination of plasma diagnostics by Langmuir probes and plasma modeling provided the data on internal plasma parameters, gas-phase chemistry and steady-state densities of plasma active species. The compositional changes of the etched surfaces were investigated using X-ray photoelectron spectroscopy (XPS). It was found that the fluorine-based etching chemistry provides the much lower halogen atom flux together with the much higher KNbxOy etching rate under the condition of quite close ion momentum fluxes in both gas systems. The correlations between measured etching rates and model-predicted fluxes of active species suggested the neutral-flux-limited etching regime with the much lower effective reaction probability between KNbxOy and Cl atoms. The last effect may be related to lower volatility of NbClx compared with NbFx (that is confirmed by XPS data) as well as to the higher energy threshold for KNbxOy + Cl reaction. [ABSTRACT FROM AUTHOR]

In-situ neutron diffraction measurements have been performed on IMI-24 grade (20% porosity) and PG25 (48% porosity) graphite subjected to external uni-axial compression loading. The 'pore free' matrix properties such as modulus of elasticity of about 72 GPa and 46 GPa were measured for the IMI-24 and PG25, respectively, and were higher than those measured at the macro-length-scale. The elastic modulus of each crystal plane, hkl, is reported ranging from about 48–145 GPa and Poisson ratio ranging from 0.08–0.28 for IMI-24 graphite. With the proposed method, the pore morphology factor 'm' was independently evaluated to be 10.8 and 4.8 for IMI-24 and PG25, respectively. It has been demonstrated from that the micro-diffraction the Young modulus is not dependent on the pore morphology factor. We consider and discuss the experimental plus modelling approach to provide a new perspective on the micro-mechanics of porous graphites. [ABSTRACT FROM AUTHOR]

Introduction: Hemivertebrae excision with local posterior instrumentation is the most common technique for treatment of patients with congenital spine deformity-it is performed at a very young age. We conducted a comparative analysis for accuracy of pedicle screw positioning in infants with congenital scoliosis of the thoracolumbar area inserted using freehand technique in vivo and 3D-printed guiding templates in vitro.Methods: The study analyzes the results of 10 surgically treated patients with congenital deformity of the thoracolumbar spine due to vertebrae failure of formation. These patients were included in group 1 (in vivo) comprising six boys and four girls with a mean age of 3 years 8 months (2 years 2 months-6 years 8 month). Group 2 (in vitro) consisted of 27 plastic 3D-printed models of congenitally deformed spine of the same 10 patients in which screws were placed using 3D-printed guiding templates. The accuracy of screw position was assessed using computer tomography data performed postoperatively with Gertzbein-Robbins classification.Results: Results of our study show that screw insertion using 3D-printed guiding templates during surgical treatment of infants with congenital spine deformities is more accurate than using freehand technique (96.3% vs. 78.8% p = 0.011).Conclusion: The data show that this method of screw insertion is very promising and can be used in surgical treatment of infants with congenital spine deformities. [ABSTRACT FROM AUTHOR]

Patients with diabetes have an increased risk of vascular complications. Suv39h1, a histone methyltransferase, plays a protective role against myocardial injury in diabetes. Herein, we intend to explore whether Suv39h1 could affect neointimal formation after vascular injury in diabetic rats and reveal the underlying mechanism. In this study, we generated adenovirus expressing Suv39h1 as well as lentivirus expressing Suv39h1‐targeting shRNA and evaluated the significance of Suv39h1 in vascular smooth muscle cells (VSMCs) under diabetic conditions. In vitro, we examined proliferative and migratory behaviours as well as the underlying signalling mechanisms in VSMCs in response to high glucose treatment. In vivo, we induced diabetes in SD rats with streptozocin and established the common carotid artery balloon injury model. Suv39h1 was found to be both necessary and sufficient to promote VSMC proliferation and migration under high glucose conditions. We observed corresponding changes in intracellular signalling molecules including complement C3 and phosphor‐ERK1/2. However, either up‐regulating or down‐regulating Suv39h1, phosphor‐p38 level was not significantly affected. Consistently, Suv39h1 overexpression led to accelerated neointima formation, while knocking down Suv39h1 reduced it following carotid artery injury in diabetic rats. Using microarray analyses, we showed that altering the Suv39h1 level in vivo dramatically altered the expression of myriad genes mediating different biological processes and molecular function. This study reveals the novel role of Suv39h1 in VSMCs of diabetes and suggests its potential role as a therapeutic target in diabetic vascular injury. [ABSTRACT FROM AUTHOR]

A unique feature of cordierite is the negative thermal expansion of its c‐axis, while the a‐ and b‐axes show positive thermal expansion behavior. The thermal expansion mechanism of cordierite has been investigated in many theoretical studies, but the effect of Ti or Ge doping has not yet been studied theoretically. Here, we investigate the thermal expansion behavior of Ti‐ and Ge‐doped cordierite by ab initio molecular dynamics (AIMD) simulation. The computational cost of AIMD simulation for cordierite doped with Ti or Ge is challenging due to the many different configurations of crystal models. We overcame this computational difficulty by separating the respective models into groups with identical symmetry, then we performed MD simulation for each different symmetry crystal model. To understand the mechanism of the negative thermal expansion of the c‐axis, we investigated the changes in all the bond lengths and angles. We found that the negative thermal expansion of the c‐axis is coupled with the increase in the O–Al–O angle and the shrinkage of the O–Si–O angle at the T1 site in cordierite, which suggests the rotation of the six‐membered ring. This study provides insight into the mechanism of thermal expansion of cordierite with Ti and Ge doping. Moreover, the approach presented here can be generally applied to investigate the thermal expansion behavior of other ceramic materials within reasonable accuracy and computational cost. [ABSTRACT FROM AUTHOR]

In this study, the concentrations of sodium, copper, and oxygen atoms in the ground state were obtained on the basis of spectral measurements. The values of concentrations agree with the results of kinetic studies of condensate accumulation. The modeling of the formation processes and further transformations of active particles in atmospheric pressure discharge plasma with a sodium chloride solution used as a cathode was performed. Experimental data on the composition of the gas phase and the physical parameters of plasma were used in the numerical simulation. The calculations were carried out using experimental values of E/N and gas temperatures for the discharge currents range of 10–70 mA. The concentrations of many active particles (O2(a1Δg), O2(b1Σg+), O(3P), NO, H2O2, OH, HO2) in the gas phase were determined. The channels of influence of the transfer processes on the properties of the discharge were established. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) affects ~ 40% of patients with diabetes and is associated with high mortality rates. Among different cellular targets in DKD, podocytes, highly specialized epithelial cells of the glomerular filtration barrier, are injured in the early stages of DKD. Both clinical and experimental data support the role of preserved insulin signaling as a major contributor to podocyte function and survival. However, little is known about the key modulators of podocyte insulin signaling. This review summarizes the novel knowledge that intracellular lipids such as cholesterol and sphingolipids are major determinants of podocyte insulin signaling. In particular, the implications of these lipids on DKD development, progression, and treatment will be addressed. [ABSTRACT FROM AUTHOR]