Multiple Chemical Features Impact Biological Performance Diversity of a Highly Active Natural Product-Inspired Library

A systematic, diversity-oriented synthesis approach was employed to access a natural product-inspired flavonoid library with diverse chemical features, including chemical properties, scaffold, stereochemistry, and appendages. Using Cell Painting, the effects of these diversity elements were evaluated, and multiple chemical features that predict biological performance diversity were identified. Scaffold identity appears to be the dominant predictor of performance diversity, but stereochemistry and appendages also contribute to a lesser degree. In addition, the diversity of chemical properties contributed to performance diversity, and the driving chemical property was dependent on the scaffold. These results highlight the importance of key chemical features that may inform the creation of small-molecule, performance-diverse libraries to improve the efficiency and success of high-throughput screening campaigns.     

Cachexia,a Systemic Disease beyond Muscle Atrophy

Cachexia is a complication of dismal prognosis, which often represents the last step of several chronic diseases. For this reason, the comprehension of the molecular drivers of such a condition is crucial for the development of management approaches. Importantly, cachexia is a syndrome affecting various organs, which often results in systemic complications. To date, the majority of the research on cachexia has been focused on skeletal muscle, muscle atrophy being a pivotal cause of weight loss and the major feature associated with the steep reduction in quality of life. Nevertheless, defining the impact of cachexia on other organs is essential to properly comprehend the complexity of such a condition and potentially develop novel therapeutic approaches.     

Effect of rheology and humic acids on the transport of environmental fluids: Potential implications for soil remediation revealed through microfluidics

This study investigated the potential effect of shear rheology and humic acids (HA) on the subsurface transport of polymeric fluids used for the remediation of contaminants. Polymeric fluids were prepared with guar, scleroglucan, and carboxymethyl cellulose (CMC). Guar fluids can be used to suspend reactive particles for contaminant degradation. Fluids prepared with 2.5 g/L of guar in water were viscous, and the crosslinker borax (1 g/L) made them viscoelastic. Microfluidics experiments showed that the increase in elasticity blocked the flow of guar in 350 μm channels. Guar, CMC, or scleroglucan fluids containing sodium thiosulfate can be used to trap toxic Cr(VI) in the subsurface and reduce it to harmless Cr(III). Trapping of Cr(VI) is achieved by the gelation of the fluids upon contact with chromium. Before mixing with chromium, HA did not affect the flow of CMC, guar, and scleroglucan in microfluidic channels. Quartz-crystal microbalance with dissipation monitoring experiments indicates that HA reduced sorption of guar onto silica, potentially promoting the transport of guar fluids in sandy aquifers. While HA slightly decreased the rate of gelation of CMC and scleroglucan upon contact with chromium, it did not affect the fast gelation rate of guar. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48465.     

Solid Fat Content as a Substitute for Total Polar Compound Analysis in Edible Oils

The solid fat contents (SFC) of heated edible oil samples were measured and found to correlate positively with total polar compounds (TPC) and inversely with triglyceride concentration. Traditional methods for determination of TPC require a laboratory setting and are time and solvent intensive. Therefore, SFC analysis represents a viable user-friendly alternative to measuring total polar components in environments where low-resolution NMR may already be in use, for example, in quality assurance environments. The slope of SFC measurements versus time was also found to correlate with the oxidative stability index of the edible oils studied.     

The role of tryptophan in protein fibrillogenesis: relevance of Trp7 and Trp14 to the amyloidogenic properties of myoglobin

In order to understand the role of tryptophan in the mechanisms of fibrils formation, the ability of a series of analogs of the residue 7-18 span of myoglobin to form amyloid-like fibrils was investigated. Alternatively one or both tryptophans were substituted with alanine and leucine, to determine the contribution of hydrophobicity and aromaticity. The scale of aggregation propensity of the peptides determined indicates that tryptophan is crucial for the amyloidogenic process. Since the rare tryptophan residue is generally engaged in structural roles in proteins, or when exposed serves as binding sites, we surmise that its exposure in the amyloidogenic fragments allows for intermolecular clustering with residues from other molecules leading to the formation of amyloid aggregates.     

Identification of vivianite,an unusual blue pigment,in a sixteenth century painting and its implications

Vivianite, a blue pigment employed in the past practically only in Northern and Central Europe, but with very limited use, was identified in an early sixteenth century painting, stylistically with Flemish features, from a church in Portugal. The identification of this iron phosphate mineral was made by SEM‐EDS based on the atomic ratio between phosphorus and iron in layers of blue paint (area analysis) and in particles of these same layers (spot analysis). This painting, about which there is no document to prove its authorship, becomes the first case, known in detail, of a sixteenth century painting containing vivianite. Moreover, this find and the presence of a chalk ground, also identified, strongly support the hypothesis of being a Flemish painting.     

The Composition of Mixed Micelles Formed by Dodecyl Trimethyl Ammonium Bromide and Benzethonium Chloride in Water

The composition of the mixed micelles formed by benzethonium chloride and dodecyl trimethyl ammonium bromide in water were experimentally determined by a combination of surfactant ion-selective electrodes and UV–Vis spectroscopy measurements. Results were compared with the computed compositions from three theories on mixed micelles available in the literature (Regular Solution, Motomura’ and Georgiev’s). The basis of the Junquera and Aicart method and the determination of the micelle aggregation number (N) by pyrene fluorescence quenching, i.e., the constancy of N and the mixed micelle composition when the total concentration is changed, were not supported by our experimental results. Experimental micelle compositions were statistically equal to those computed by Regular Solution Theory. The mixed micelle composition and the quantity of non-micellized surfactant molecules change with concentration above the critical micelle concentration, and therefore do not support the assumptions used in the Junquera and Aicart procedure and in the determination of N by pyrene fluorescence quenching. The reason why the latter procedure gives N values similar to those obtained from other techniques is discussed.     

Thermochemical model on the carbothermal reduction of oxides during spark plasma sintering of zirconium diboride

Carbon was used to reduce oxides in spark plasma sintered ZrB₂ ultra-high temperature ceramics. A thermodynamic model was used to evaluate the reducing reactions to remove B₂O₃ and ZrO₂ from the powder. Powder oxygen content was measured and carbon additions of 0.5 and 0.75 wt% were used. A C–ZrO₂ pseudo binary diagram, ZrO₂–B₂O₃–C pseudo ternaries, and Zr–C–O potential phase diagrams were generated to show how the reactions can be related to an open system experiment in the tube furnace. Scanning transmission electron microscopy identified impurity phases composed of amorphous Zr–B–O with lamellar BN and a Zr–C–O ternary model was calculated under SPS sintering conditions at 1900°C and 6 Pa to understand how oxides can be retained in the microstructure.     

Direct and Indirect Effect of TGFβ on Treg Transendothelial Recruitment in HCC Tissue Microenvironment

The balance between anti-tumor and tumor-promoting immune cells, such as CD4+ Th1 and regulatory T cells (Tregs), respectively, is assumed to dictate the progression of hepatocellular carcinoma (HCC). The transforming growth factor beta (TGFβ) markedly shapes the HCC microenvironment, regulating the activation state of multiple leukocyte subsets and driving the differentiation of cancer associated fibroblasts (CAFs). The fibrotic (desmoplastic) reaction in HCC tissue strongly depends on CAFs activity. In this study, we attempted to assess the role of TGFβ on transendothelial migration of Th1-oriented and Treg-oriented CD4+ T cells via a direct or indirect, CAF-mediated mechanisms, respectively. We found that the blockage of TGFβ receptor I-dependent signaling in Tregs resulted in impaired transendothelial migration (TEM) of these cells. Interestingly, the secretome of TGFβ-treated CAFs inhibited the TEM of Tregs but not Th1 cells, in comparison to the secretome of untreated CAFs. In addition, we found a significant inverse correlation between alpha-SMA and FoxP3 (marker of Tregs) mRNA expression in a microarray analysis involving 78 HCCs, thus suggesting that TGFβ-activated stromal cells may counteract the trafficking of Tregs into the tumor. The apparent dual behavior of TGFβ as both pro- and anti-tumorigenic cytokines may add a further level of complexity to the mechanisms that regulate the interactions among cancerous, stromal, and immune cells within HCC, as well as other solid tumors, and contribute to better manipulation of the TGFβ signaling as a therapeutic target in HCC patients.