Structural Determinants of the Selectivity of 3‐Benzyluracil‐1‐acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10

The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3 ) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4 ), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells.     

Synthesis and characterization of the polyols by air oxidation of soybean oil and its effect on the morphology and dynamic mechanical properties of poly(vinyl chloride) blends

The use of natural additives, with low toxicity and good compatibility, for PVC is becoming increasingly attractive. In this study, soybean oil additives were prepared by air oxidation reactions and blending with PVC. The oxidation reaction produced a significant increase in the number of hydroxyl groups in soybean oil; however, this kind of reaction results in the formation of a heterogeneous structure due to free radical reactions in the medium. The oxidized soybean oil improved the compatibility with PVC due to an increase in the number of polar groups, such as hydroxyls, and thus a reduction in the amount of atactic polymer was observed. Furthermore, an increase in the molecular weight of the oxidized oil, as well as large amounts of polar groups contributes to reducing the migration of oil in the PVC. Regarding the crystallinity of PVC, the use of pure and oxidized soybean oil causes small changes in the crystalline phase of the polymer. Oxidized soybean oil has great potential for usage as a secondary plasticizer for PVC. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42102.     

Effects of composition and furnace temperature on (Ni,Co) (Cr,Al)2O4 pigments synthesized by solution combustion route

The effects of composition and furnace temperature on Ni_1‐ΨCo_ΨCr_2?2ΨAl_2ΨO₄ (0≤Ψ≤1) pigments prepared by Solution Combustion Synthesis were studied. As‐synthesized samples showed spinel‐like spongy structure, very easy to grind. However, important differences on crystallinity, crystal size, and microstructure were observed depending on composition and furnace temperature. All pigments developed intense tones, covering a wide color palette because of composition influence, although little effect was observed with furnace temperature. Stable crystalline structures, suitable grain size, and high resistance against synthesizing variables and ceramic glazes make SCS pigments perfect candidates to be used in the ceramic ink‐jet decoration.     

On the steady‐state drop size distribution in stirred vessels. Part I: Effect of dispersed phase viscosity

Previous studies on emulsification have used the maximum drop size (d_max) or Sauter mean diameter ( ) to investigate the effect of viscosity on the drop size distribution (DSD), however, these parameters fall short for highly polydispersed emulsions. In this investigation (Part I), the steady‐state DSD of dilute emulsions is studied using of silicon oils with viscosities varying across six orders of magnitude at different stirring speeds. Different emulsification regimes were identified; our modeling and analysis is centered on the intermediate viscosity range where interfacial cohesive stresses can be considered negligible and drop size increases with viscosity. The bimodal frequency distributions by volume were well described using two log‐normal density functions. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3293–3302, 2018     

Characterisation of surface oxidation of nickel-titanium alloy by ion-beam and electrochemical techniques

The passivating effects produced on Ni₄₉Ti₅₁ (at.%) shape memory alloy by electropolishing in methanol-sulphuric acid electrolyte or thermal treatment in air are investigated with ion-beam techniques (secondary ion mass spectrometry (SIMS) and mass resolved ion scattering spectrometry (MARISS)) and electrochemical techniques (polarisation curves, photocurrent spectroscopy and impedance). Electropolishing produces a limited passivation due to formation of a thin layer of amorphous TiO₂, which causes only a slight hindrance to the oxygen evolution reaction. Thermal treatment in air at 450 °C causes a more substantial passivation due to formation of a thick oxide layer, estimated at about 80 nm for a 16 h treatment on the basis of weight increase, disregarding roughness. Data indicate that the film produced by thermal oxidation has probably a duplex structure, with a porous outer layer with inclusions of Ni species and a compact inner layer, in contact with the substrate, consisting of (essentially) nickel free TiO₂ rutile.     

Preliminary study of the anticancer applications of mesoporous materials functionalized with the natural product betulinic acid

Dehydrated MCM-41 (S1) was functionalized under nitrogen with 3-chloropropyltriethoxysilane (CPTS) and 3-aminopropyltriethoxysilane (APTS) by grafting in toluene at 80 °C over 48 h to give the corresponding materials S2 and S3, respectively. Subsequently, S2 and S3 were suspended in methanol and reacted in a nitrogen atmosphere with betulinic acid (BA) for 48 h at 65 °C (in the presence of the triethylamine of S2) to give the BA-functionalized materials S4 and S5. All materials studied were characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, multinuclear MAS NMR spectroscopy, thermogravimetry, UV spectroscopy, IR, SEM, and TEM. To study the release of BA, S4 and S5 were suspended in solutions simulating various body pH conditions (pH 7.4, 5.5, and 3.0). Results of the quantification of BA release by HPLC for S4 show a pH-dependent and very slow BA release following a logarithmic tendency, while S5 behaves differently, also pH-dependent but, in this case, fast release of BA which requires only days for total release of the therapeutic compound. In addition, the cytotoxic activity of all synthesized materials against various cancer cell lines was studied. The results show the absence of an antiproliferative effect on the surfaces without BA S1-S3, while an antiproliferative effect was observed with S4 and S5 and was attributed to the release of BA in the medium.     

Ecology and Evolution of Soil Nematode Chemotaxis

Plants influence the behavior of and modify community composition of soil-dwelling organisms through the exudation of organic molecules. Given the chemical complexity of the soil matrix, soil-dwelling organisms have evolved the ability to detect and respond to these cues for successful foraging. A key question is how specific these responses are and how they may evolve. Here, we review and discuss the ecology and evolution of chemotaxis of soil nematodes. Soil nematodes are a group of diverse functional and taxonomic types, which may reveal a variety of responses. We predicted that nematodes of different feeding guilds use host-specific cues for chemotaxis. However, the examination of a comprehensive nematode phylogeny revealed that distantly related nematodes, and nematodes from different feeding guilds, can exploit the same signals for positive orientation. Carbon dioxide (CO(2)), which is ubiquitous in soil and indicates biological activity, is widely used as such a cue. The use of the same signals by a variety of species and species groups suggests that parts of the chemo-sensory machinery have remained highly conserved during the radiation of nematodes. However, besides CO(2), many other chemical compounds, belonging to different chemical classes, have been shown to induce chemotaxis in nematodes. Plants surrounded by a complex nematode community, including beneficial entomopathogenic nematodes, plant-parasitic nematodes, as well as microbial feeders, are thus under diffuse selection for producing specific molecules in the rhizosphere that maximize their fitness. However, it is largely unknown how selection may operate and how belowground signaling may evolve. Given the paucity of data for certain groups of nematodes, future work is needed to better understand the evolutionary mechanisms of communication between plant roots and soil biota.     

Buildup of hyperbranched polymer/alginate multilayers and their influence on protein adsorption and platelet adhesion

A hyperbranched poly(methylene bisacrylamide–aminoethyl piperazine) (HPMA) and lactobionic acid modified hyperbranched poly(methylene bisacrylamide–aminoethyl piperazine) (LA–HPMA), namely, galactosylated HPMA, were assembled with alginate through the application of the layer‐by‐layer technique to fabricate polyelectrolyte multilayer (PEM) films. We monitored the assembly process to reveal the stepwise mass increase with a quartz crystal microbalance with the dissipation technique and by the reversal of the ζ potential. The thickness of PEMs assembled in solutions with different pHs was measured by spectroscopic ellipsometry; it showed a general decreasing tendency along with the pH increase. Postincubation in a buffer solution revealed that the multilayers possessed good stability with a thickness decrease from 5 to 15%. The PEMs showed a limited protein adsorption. Serum, bovine serum albumin, and fibrinogen were adsorbed onto the multilayers with a density within hundreds of nanograms per square centimeter to 1 μg/cm² and showed a relatively smaller adsorption on the multilayers assembled at pH 9. The PEMs assembled with LA–HPMA showed the lowest adhesion and activation of platelets, regardless of the outmost layer. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44769.     

The modification of indium tin oxide with phosphonic acids: mechanism of binding, tuning of surface properties, and potential for use in organic electronic applications

Transparent metal oxides, in particular, indium tin oxide (ITO), are critical transparent contact materials for applications in next-generation organic electronics, including organic light emitting diodes (OLEDs) and organic photovoltaics (OPVs). Understanding and controlling the surface properties of ITO allows for the molecular engineering of the ITO-organic interface, resulting in fine control of the interfacial chemistries and electronics. In particular, both surface energy matching and work function compatibility at material interfaces can result in marked improvement in OLED and OPV performance. Although there are numerous ways to change the surface properties of ITO, one of the more successful surface modifications is the use of monolayers based on organic molecules with widely variable end functional groups. Phosphonic acids (PAs) are known to bind strongly to metal oxides and form robust monolayers on many different metal oxide materials. They also demonstrate several advantages over other functionalizing moieties such as silanes or carboxylic acids. Most notably, PAs can be stored in ambient conditions without degradation, and the surface modification procedures are typically robust and easy to employ. This Account focuses on our research studying PA binding to ITO, the tunable properties of the resulting surfaces, and subsequent effects on the performance of organic electronic devices. We have used surface characterization techniques such as X-ray photoelectron spectroscopy (XPS) and infrared reflection adsorption spectroscopy (IRRAS) to determine that PAs bind to ITO in a predominantly bidentate fashion (where two of three oxygen atoms from the PA are involved in surface binding). Modification of the functional R-groups on PAs allows us to control and tune the surface energy and work function of the ITO surface. In one study using fluorinated benzyl PAs, we can keep the surface energy of ITO relatively low and constant but tune the surface work function. PA modification of ITO has resulted in materials that are more stable and more compatible with subsequently deposited organic materials, an effective work function that can be tuned by over 1 eV, and energy barriers to hole injection (OLED) or hole-harvesting (OPV) that can be well matched to the frontier orbital energies of the organic active layers, leading to better overall device properties.     

Lipid Transfer to HDL is Higher in Marathon Runners than in Sedentary Subjects,but is Acutely Inhibited During the Run

Although exercise increases HDL-cholesterol, exercise-induced changes in HDL metabolism have been little explored. Lipid transfer to HDL is essential for HDL’s role in reverse cholesterol transport. We investigated the effects of acute exhaustive exercise on lipid transfer to HDL. We compared plasma lipid, apolipoprotein and cytokine levels and in vitro transfer of four lipids from a radioactively labeled lipid donor nanoemulsion to HDL in sedentary individuals (n = 28) and in marathon runners (n = 14) at baseline, immediately after and 72 h after a marathon. While HDL-cholesterol concentrations and apo A1 levels were higher in marathon runners, LDL-cholesterol, apo B and triacylglycerol levels were similar in both groups. Transfers of non-esterified cholesterol [6.8 (5.7–7.2) vs. 5.2 (4.5–6), p = 0.001], phospholipids [21.7 (20.4–22.2) vs. 8.2 (7.7–8.9), p = 0.0001] and triacylglycerol [3.7 (3.1–4) vs. 1.3 (0.8–1.7), p = 0.0001] were higher in marathon runners, but esterified-cholesterol transfer was similar. Immediately after the marathon, LDL- and HDL-cholesterol concentrations and apo A1 levels were unchanged, but apo B and triacylglycerol levels increased. Lipid transfer of non-esterified cholesterol [6.8 (5.7–7.2) vs. 5.8 (4.9–6.6), p = 0.0001], phospholipids [21.7 (20.4–22.2) vs. 19.1 (18.6–19.3), p = 0.0001], esterified-cholesterol [3.2 (2.2–3.8) vs. 2.3 (2–2.9), p = 0.02] and triacylglycerol [3.7 (3.1–4) vs. 2.6 (2.1–2.8), p = 0.0001] to HDL were all reduced immediately after the marathon but returned to baseline 72 h later. Running a marathon increased IL-6 and TNF-α levels, but after 72 h these values returned to baseline. Lipid transfer, except esterified-cholesterol transfer, was higher in marathon runners than in sedentary individuals, but the marathon itself acutely inhibited lipid transfer. In light of these novel observations, further study is required to clarify how these metabolic changes can influence HDL composition and anti-atherogenic function.