Accurate detection of benign and malignant renal tumor subtypes with MethylBoostER: An epigenetic marker-driven learning framework.

Current gold standard diagnostic strategies are unable to accurately differentiate malignant from benign small renal masses preoperatively; consequently, 20% of patients undergo unnecessary surgery. Devising a more confident presurgical diagnosis is key to improving treatment decision-making. We therefore developed MethylBoostER, a machine learning model leveraging DNA methylation data from 1228 tissue samples, to classify pathological subtypes of renal tumors (benign oncocytoma, clear cell, papillary, and chromophobe RCC) and normal kidney. The prediction accuracy in the testing set was 0.960, with class-wise ROC AUCs >0.988 for all classes. External validation was performed on >500 samples from four independent datasets, achieving AUCs >0.89 for all classes and average accuracies of 0.824, 0.703, 0.875, and 0.894 for the four datasets. Furthermore, consistent classification of multiregion samples (N = 185) from the same patient demonstrates that methylation heterogeneity does not limit model applicability. Following further clinical studies, MethylBoostER could facilitate a more confident presurgical diagnosis to guide treatment decision-making in the future.

Remarkable Structural Modifications of Tialite Solid Solutions Obtained by Different Methods.

The structural changes occurring in tialite due to the formation of magnesium-titanate-aluminum-titanate solid solutions were determined. For this purpose, a DFT simulation of the structural changes was performed. The simulation proposed a number of possible atomic substitutions occurring in the elementary cells of the tialite, along with calculations of the lattice parameter changes in this material. Next, the actual changes occurring in the structure of the tialite due to the formation of solid solutions, obtained in different ways, were investigated. After comparing the obtained results, it was possible to confirm the mechanism of the formation of tialite solid solutions, through which one magnesium atom and one titanium atom substituted two aluminum atoms simultaneously. The results of this experimental work were confirmed by theoretical calculations (the differences in the values of the lattice parameters, measured in the experiment and calculated in the simulation, were less than 0.5%), through which changes in the lattice parameters with Mg and Ti substitution were observed.

Reactive Sintering of Dysprosium-Iron Garnet via a Perovskite-Hematite Solid State Reaction and Physical Properties of the Material.

In this paper, we report on a successful synthesis of dysprosium iron garnet Dy3Fe5O12 (DyIG) by a reactive synthesis method involving dysprosium iron perovskite and hematite. Phase formation was traced using dilatometry, and XRD measurements attested to the formation of the desired structure. Samples with relative density close to 97% were fabricated. The samples were characterized using vibrating sample magnetometry, dielectric spectroscopy, and UV-Vis-NIR spectroscopy. Magnetic properties were probed in temperatures between 80 and 700 K with a maximum applied field of 1 kOe. The measurements revealed several effects: the compensation of magnetic moments at a certain temperature, the inversion of the magnetocaloric effect, and the ability to measure the Curie temperature of the material. Activation energy was determined from UV-Vis-NIR and dielectric spectroscopy measurements. Characteristic magnetic temperatures and activation energy values of the samples were similar to bulk DyIG obtained using other methods.

Influence of the Grain Size Distribution of the Limestone Additives on the Color Properties and Phase Composition of Sintered Ceramic Materials Based on Cream-Firing Clays.

The study focused on determining color changes in materials made of cream-firing clays from the Opoczno region (Poland) due to the addition of calcium carbonate in the form of limestone. Moreover, the influence of the grain size distribution of this additive on the color properties of the materials and their phase composition was determined. Test samples were prepared using theplastic method and fired at four different temperatures: 1120, 1140, 1160 and 1180 °C. The color properties of the surface of ceramic materials were determined in CIE-Lab color space using a colorimeter. Quantitative phase analysis was performed using the Rietveld method. The research showed that the addition of calcium carbonate causes an increase in the yellow color factor and a decrease in the red color factor and the brightness of the material. Moreover, it was proven that the grain size distribution of the additive used significantly influences the phase composition of the materials, thus determining the values of physical properties and the color of the materials.

Effect of Expanded Graphite on the Reaction Sintering of Boron Carbide.

This paper presents novel results of research focused on reaction sintering of a mixture of expanded graphite and amorphous boron. It has been shown that as a result of combining the synthesis from the elements with sintering under pressure, dense boron carbide polycrystals (95% TD) can be obtained in which stable structures dominate, i.e., boron carbides of stoichiometry B13C2 and B4C. Sintering was carried out on boron excess systems, and reaction mixtures with the following mass ratios (B:C = 5:1; 10:1; and 15:1) were used. Boron excess systems were used due to the presence of additional carbon during sintering since the matrix, reactor lining, and heating elements were made of graphite. 1850 °C was considered to be the optimum reaction sintering temperature for all of the systems tested. This shows that a reduction in the sintering temperature of 200-300 °C was observed with respect to traditional sintering techniques. Micro-cracks are present in the sinters, the presence of which is most likely due to the difficulty in removing the gaseous products which accompany the boron carbide synthesis reaction. The elimination of these defects of sintering requires further research.

Investigating the Crystallization Process of Boron-Bearing Silicate-Phosphate Glasses by Thermal and Spectroscopic Methods.

Glasses and devitrificates from the SiO2-B2O3-P2O5-K2O-CaO-MgO system with constant contents of SiO2 and P2O5 network formers, modified by the addition of B2O3, were analyzed. All materials were synthesized by the traditional melt-quenching technique. The glass stability (GS) parameters (Krg, ∆T, KW, KH) were determined. The effect of the addition of B2O3 on the GS, liquation phenomenon, crystallization process, and the type of crystallizing phases were examined using SEM-EDS, DSC, XRD, and Raman spectroscopy imaging methods. It was observed that the addition of B2O3 increased the tendency of the glass to crystallize. Both phosphates (e.g., Ca9MgK(PO4)7, Mg3Ca3(PO4)4), and silicates (e.g., K2Mg5(Si12O30), CaMg(Si2O6), MgSiO3) crystallized in the studied system. The Raman spectrum for the orthophosphate Mg3Ca3(PO4)4 stanfieldite type was obtained. Boron ions were introduced into the structures of crystalline compounds at high crystallization temperatures. The type of crystallizing phases was found to be related to the phenomenon of liquation, and the order of their occurrence was dependent on the Gibbs free enthalpy.

Comparison of Precursor Preparation Routes on Final Density of Y3Fe5O12 Garnets Prepared via Reactive Sintering.

Yttrium iron garnet was obtained using four methods of synthesis. A modified citrate method and a modified citrate method with YIG (yttrium iron garnet, Y3Fe5O12) nucleation were used. In two subsequent methods, YIP (yttrium iron perovskite, YFeO3) and α-Fe2O3 obtained in the first case by the citrate method and in the second by precipitation of precursors with an ammonia solution were used as the input precursors for reaction sintering. Differential scanning calorimetry (DSC) measurements of the output powders obtained by all methods allowed to identify the effects observed during the temperature increase. Dilatometric measurements allowed to determine the changes in linear dimensions at individual stages of reaction sintering. In the case of materials obtained by the citrate method, two effects occur with the increasing temperature, the first of which corresponds to the reaction of the formation of yttrium iron perovskite (YIP), and the second is responsible for the reaction of the garnet (YIG) formation. However, in the case of heat treatment of the mixture of YIP and α-Fe2O3, we observe only the effect responsible for the solid state reaction leading to the formation of yttrium iron garnet. The obtained materials were reaction sintered at temperatures of 1300 and 1400 °C. Only in the case of material obtained from a mixture of perovskite and iron(III) oxide obtained by ammonia precipitation at temperature of 1400 °C were densities achieved higher than 98% of the theoretical density. The use of Hot Isostatic Pressing (HIP) in the case of this material allowed to eliminate the remaining porosity and to obtain full density.

Hydrothermal Aging of ATZ Composites Based on Zirconia Made of Powders with Different Yttria Content.

The presented work concerns the development and investigation of three different grades of ZrO2 materials containing Al2O3 particles (ATZ-Alumina Toughened Zirconia ceramics with 2.3-20 vol.% of alumina). The zirconia powders containing 3 mol.% of yttria were synthesized by a precipitation/calcination method and fabricated from two different zirconia powders with different yttria content. Then, the selected ATZ composites (ATZ-B, ATZ-10 and ATZ-20) were prepared by means of conventional mixing, compacting and sintering at 1450 °C for 1.5 h. The phase composition, microstructure, relative density and basic mechanical properties were determined. Uniform microstructures with relative densities over 99% of theoretical density, hardness values between 12.0-13.8 GPa, flexural strength up to 1 GPa and outstanding fracture toughness of 12.7 MPa⋅m1/2 were obtained. The aging susceptibility of alumina toughened zirconia materials, as a consequence of hydrothermal treatment, was investigated. The aim of this study was to determine the influence of LTD (low temperature degradation) on the tetragonal to monoclinic phase transitions and on the flexural strength of hydrothermally aged specimens. The results were compared to those obtained for commercially available tetragonal zirconia-based materials containing 3 mol.% of yttria. This research shows that ATZ composites that have excellent mechanical properties and sufficient hydrothermal aging resistance can be attained and later used in technical and biomedical applications.

The Utilisation of Solid Fuels Derived from Waste Pistachio Shells in Direct Carbon Solid Oxide Fuel Cells.

The comprehensive results regarding the physicochemical properties of carbonaceous materials that are obtained from pistachio shells support their usage as solid fuels to supply direct carbon solid oxide fuel cells (DC-SOFCs). The influence of preparation conditions on variations in the chemical composition, morphology of the biochar powders, and degree of graphitization of carbonaceous materials were investigated. Based on structural investigations (X-ray diffraction analysis and Raman spectroscopy), it was observed that disordered carbon particles developed during the application of thermal treatments. The use of X-ray fluorescence enabled a comparative analysis of the chemical composition of the inorganic matter in biocarbon-based samples. Additionally, the gasification of carbonaceous-based samples vs. time at a temperature of 850 °C was investigated in a H2O or CO2 gas atmosphere. The analysis demonstrated the conversion rate of biochar obtained from pistachio shells to H2, CH4 and CO during steam gasification. The electrochemical investigations of the DC-SOFCs that were supplied with biochars obtained from pistachio shells were characterized by satisfactory values for the current and power densities at a temperature range of 700-850 °C. However, a higher power output of the DC-SOFCs was observed when CO2 was introduced to the anode chamber. Therefore, the impact of the Boudouard reaction on the performance of DC-SOFCs was confirmed. The chars that were prepared from pistachio shells were adequate for solid fuels for utilization in DC-SOFCs.

Search for mid- and high-entropy transition-metal chalcogenides - investigating the pentlandite structure.

For the first time, transition metal-based chalcogenides conforming to the definition of high entropy materials, are synthesized, with the multicomponent occupation being utilized on both cationic and anionic sublattices. The pentlandite-structured (Co,Fe,Ni)9S8 and (Co,Fe,Ni)9(S,Se)8 compositions are obtained using a two-stage, solid-state reaction method. Room temperature structural analysis (XRD, SEM, Raman) in both cases indicates the presence of a homogeneous, single-phase, Fm3[combining macron]m structure, with a profound effect of Se addition on the lattice parameters. The obtained materials possess an excellent electrical conductivity of 105 S m-1, and slightly negative Seebeck coefficient values, resulting from their metallic character, combined with a low thermal conductivity of 2.5 W m-1 K-1, especially when compared with conventional analogues. The optical measurements reveal very promising behavior in the UV/vis range. The electrochemical sensitivity towards hydrazine and acetaminophen is also presented, making them potentially interesting for sensor devices. Based on the DFT analysis of various sub-systems, the origins of the observed transport and optical behavior are explained. Furthermore, it is shown that the application of the high-entropy principle to both sublattices simultaneously allows for extensive tailoring of the band structure, allowing these materials to be optimized with respect to the given application, including thermoelectric and photoelectrochemical devices and catalysis, e.g., the hydrogen evolution reaction.

Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells.

Circadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.

Bioactive hydrogel scaffolds reinforced with alkaline-phosphatase containing halloysite nanotubes for bone repair applications.

Alkaline phosphatase (ALP), biomineralization promoting enzyme, was immobilized in halloysite (HAL) nanotubes and used as a bioactive component of the chitosan (CH) and chitosan-collagen (C-CH) hydrogel scaffolds for bone regeneration. The influence of HAL-ALP and collagen on the properties of the obtained materials was studied. 30 wt% of HAL-ALP increased significantly the swelling ratio of chitosan-based scaffolds. The presence of both: collagen and HAL-ALP had positive effect on the scaffolds' porosity, which was considerably higher for C-CH. The presence of HAL has improved the mechanical properties of both types of scaffolds, while the addition of 20% of collagen to the chitosan hydrogels have considerably decreased their storage modulus. Biomineralization tests showed that although mineral was formed in both CH and C-CH scaffolds with HAL-ALP, the process was more effective for collagen-containing hydrogels. Biological studies, performed using MG-63 osteoblast-like cell line showed that C-CH scaffolds, especially those after biomineralization, were a better material for cell adhesion and growth. Both types of scaffolds degraded slowly in physiological pH. C-CH scaffolds containing 30% of HAL-ALP have the highest potential as bioactive material for bone regeneration.

Samples of Ba1-xSrxCe0.9Y0.1O3-δ, 0 < x < 0.1, with Improved Chemical Stability in CO2-H2 Gas-Involving Atmospheres as Potential Electrolytes for a Proton Ceramic Fuel Cell.

Comparative studies were performed on variations in the ABO3 perovskite structure, chemical stability in a CO2-H2 gas atmosphere, and electrical conductivity measurements in air, hydrogen, and humidity-involving gas atmospheres of monophase orthorhombic Ba1-xSrxCe0.9Y0.1O3-δ samples, where 0 < x < 0.1. The substitution of strontium with barium resulting in Ba1-xSrxCe0.9Y0.1O3-δ led to an increase in the specific free volume and global instability index when compared to BaCe0.9Y0.1O3-δ. Reductions in the tolerance factor and cell volume were found with increases in the value of x in Ba1-xSrxCe0.9Y0.1O3-δ. Based on the thermogravimetric studies performed for Ba1-xSrxCe0.9Y0.1O3-δ, where 0 < x < 0.1, it was found that modified samples of this type exhibited superior chemical resistance in a CO2 gas atmosphere when compared to BaCe0.9Y0.1O3-δ. The application of broadband impedance spectroscopy enabled the determination of the bulk and grain boundary conductivity of Ba1-xSrxCe0.9Y0.1O3-δ samples within the temperature range 25-730 °C. It was found that Ba0.98Sr0.02Ce0.9Y0.1O3-δ exhibited a slightly higher grain interior and grain boundary conductivity when compared to BaCe0.9Y0.1O3-δ. The Ba0.95Sr0.05Ce0.9Y0.1O3-δ sample also exhibited improved electrical conductivity in hydrogen gas atmospheres or atmospheres involving humidity. The greater chemical resistance of Ba1-xSrxCe0.9Y0.1O3-δ, where x = 0.02 or 0.05, in a CO2 gas atmosphere is desirable for application in proton ceramic fuel cells supplied by rich hydrogen processing gases.

Bioactive yet antimicrobial structurally stable collagen/chitosan/lysine functionalized hyaluronic acid - based injectable hydrogels for potential bone tissue engineering applications.

Novel, biocompatible, multifunctional, injectable genipin crosslinked collagen/chitosan/lysine-modified hyaluronic acid based hydrogels (ColChHAmod) were prepared in a facile, one-step procedure. The novelty of the current approach lies in the functionalization of hyaluronic acid (HA) with primary amine groups by lysine attachment, and its further use as a component of the injectable sol. The obtained derivative, HAmod, could form, upon crosslinking with genipin, covalent bonds with other components of the hydrogel network, resulting in structurally stable, better-defined hydrogels. We have demonstrated that, by adjusting HAmod content and genipin concentration, hydrogels with tunable physicochemical characteristics (swelling, wettability, tendency for enzymatic degradation) and properties adequate for the potential bone tissue regeneration can be prepared. Storage modulus measurements indicated that HAmod has positive effect on mechanical characteristics of hydrogels prepared. It was also revealed that the ColChHAmod-based hydrogels are characterized by a high porosity (85-95%). The in situ rheological measurements confirmed the injectability of the obtained hydrogels. The in vitro cell culture studies showed that the surface of all materials prepared was biocompatible, as they supported proliferation and adhesion of osteoblast-like cells followed by ALP expression. The intrinsic antibacterial activity of the hydrogels against Escherichia coli was also demonstrated in in vitro experiment.

Phenotypic proteomic profiling identifies a landscape of targets for circadian clock-modulating compounds.

Determining the exact targets and mechanisms of action of drug molecules that modulate circadian rhythms is critical to develop novel compounds to treat clock-related disorders. Here, we have used phenotypic proteomic profiling (PPP) to systematically determine molecular targets of four circadian period-lengthening compounds in human cells. We demonstrate that the compounds cause similar changes in phosphorylation and activity of several proteins and kinases involved in vital pathways, including MAPK, NGF, B-cell receptor, AMP-activated protein kinases (AMPKs), and mTOR signaling. Kinome profiling further indicated inhibition of CKId, ERK1/2, CDK2/7, TNIK, and MST4 kinases as a common mechanism of action for these clock-modulating compounds. Pharmacological or genetic inhibition of several convergent kinases lengthened circadian period, establishing them as novel circadian targets. Finally, thermal stability profiling revealed binding of the compounds to clock regulatory kinases, signaling molecules, and ubiquitination proteins. Thus, phenotypic proteomic profiling defines novel clock effectors that could directly inform precise therapeutic targeting of the circadian system in humans.

The Effect of Calcination Temperature on the Structure and Performance of Nanocrystalline Mayenite Powders.

The effect of calcination temperature on the structural properties and phase formation of synthesized CaO-Al2O3 nanopowder was investigated and discussed. The calcination products were identified by differential thermal analysis (DTA) and the crystalline phase formation was analyzed by X-ray diffraction (XRD). The obtained results showed that the crystallization started at 460 °C. Finally, the microstructures of the nanoparticles were observed by scanning (SEM) and transmission electron (TEM) microscopes. The investigation showed that an increase in the calcination temperature led to the appreciable increase in the crystallite size and the crystallinity of the final product. The obtained data confirmed that the prepared materials were mayenite with different surface area in the range of 71.18 m2/g to 10.34 m2/g after annealing in the temperature range of 470 °C to 960 °C.

Short- and long-term retrogradation of potato starches with varying amylose content.

BACKGROUND: Gels of potato starches with varying amylose content were prepared and the degree of pasting and the course of retrogradation were studied. The average molar masses of granular and pasted starches were estimated. Determination of the degree of pasting involved use of optical microscopy and the study of pasting characteristics. The studies of susceptibility to retrogradation considered mechanical spectra, hardness, syneresis, resistant starch content, and X-ray measurements. RESULTS: Heating of the starch suspensions at 95 °C resulted in almost complete deterioration of granules. Changes in storage modulus (G') exceeded these of loss modulus (G"). Values of G' and G", hardness and syneresis increased with the period of the sample storage and, simultaneously, the relevant tangent of the phase shift angle (tg (G"/G')) decreased. A tendency was observed for the resistant starch (RS) content to increase on prolonged storage of gels. The patterns of diffractograms for the pasted and lyophilized samples only differed slightly. CONCLUSION: The pastes of all the studied potato starches were characterized by a similar degree of pasting. The most essential changes in the physicochemical properties of the gels were observed between the 30th and 90th days of storage. The susceptibility of potato starch gels to retrogradation, especially within the first 2 h, was controlled, mainly by the amylose content. © 2018 Society of Chemical Industry.

Cationic derivatives of dextran and hydroxypropylcellulose as novel potential heparin antagonists.

Cationic derivatives of dextran (Dex) and hydroxypropylcellulose (HPC) were studied as potential alternatives of protamine sulfate (PS) used in the reversal of anticoagulant activity of heparin. The modification was performed by the attachment of cationic groups to the Dex main chain or by grafting short side chains of a polycation onto HPC. The cationic derivatives of these polysaccharides were found to bind heparin with the efficiency increasing with growing degree of cationic modification. The degree of cationic modification and consequently the ζ potential of the polymers do not have to be high to achieve effective heparin binding. The size of the complexes of cationic Dex with unfractionated heparin (UFH) is a few micrometers. For complexes of cationic HPC and UFH the size is much below 1 µm, both below and above the lower critical solution temperature of HPC. None of the cationic polysaccharides studied caused hemolysis. The concentrations of the polymers inducing the aggregation of human erythrocytes in vitro were determined.