Dichloroacetate Radiosensitizes Hypoxic Breast Cancer Cells

Mitochondrial metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways can potentially sensitize tumors with limited treatment options, such as triple-negative breast cancer (TNBC), to chemo- and/or radiotherapy. Dichloroacetate (DCA) is a specific inhibitor of the pyruvate dehydrogenase kinase (PDK), which leads to enhanced reactive oxygen species (ROS) production. ROS are the primary effector molecules of radiation and an increase hereof will enhance the radioresponse. In this study, we evaluated the effects of DCA and radiotherapy on two TNBC cell lines, namely EMT6 and 4T1, under aerobic and hypoxic conditions. As expected, DCA treatment decreased phosphorylated pyruvate dehydrogenase (PDH) and lowered both extracellular acidification rate (ECAR) and lactate production. Remarkably, DCA treatment led to a significant increase in ROS production (up to 15-fold) in hypoxic cancer cells but not in aerobic cells. Consistently, DCA radiosensitized hypoxic tumor cells and 3D spheroids while leaving the intrinsic radiosensitivity of the tumor cells unchanged. Our results suggest that although described as an oxidative phosphorylation (OXPHOS)-promoting drug, DCA can also increase hypoxic radioresponses. This study therefore paves the way for the targeting of mitochondrial metabolism of hypoxic cancer cells, in particular to combat radioresistance.     

A Fluorometric Enzymatic Assay for Quantification of Steryl Glucosides in Biodiesel

Steryl glucosides (SG) are common contaminants in biodiesel that form precipitates, which form and cause problems due to fouling during transport and storage. Therefore, their quantification is necessary to assess the quality of this fuel. The methods currently available for SG analysis require expensive instrumentation, need a previous concentration step by solid‐phase extraction (SPE) or are of limited use for the quantitative assessment. We developed an enzymatic method for SG quantification in biodiesel samples based on the hydrolysis of the glucoside catalyzed by a broadly specific beta glucosidase and the subsequent determination of the glucose released by the reaction. The method is non‐expensive, sensitive and was adapted to 96‐well format fluorescence plate reader, making it useful for the parallel assay of multiple samples. The enzymatic assay presented here represent a valuable tool for both quality control and the development of improved biodiesel production and purification procedures.     

Ile-1781-Leu and Asp-2078-Gly Mutations in ACCase Gene,Endow Cross-resistance to APP,CHD, and PPZ in Phalaris minor from Mexico

Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase) are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor). These herbicides are classified into three major families (ariloxyphenoxypropionates (APP), cyclohexanodiones (CHD), and, recently, phenylpyrazolines (PPZ)). In this work, the resistance to ACCase (APP, CHD, and PPZ) inhibiting herbicides was studied in a biotype of Phalaris minor (P. minor) from Mexico, by carrying out bioassays at the whole-plant level and investigating the mechanism behind this resistance. Dose-response and ACCase in vitro activity assays showed cross-resistance to all ACCase herbicides used. There was no difference in the absorption, translocation, and metabolism of the ¹⁴C-diclofop-methyl between the R and S biotypes. The PCR generated CT domain fragments of ACCase from the R biotype and an S reference were sequenced and compared. The Ile-1781-Leu and Asp-2078-Gly point mutations were identified. These mutations could explain the loss of affinity for ACCase by the ACCase-inhibing herbicides. This is the first report showing that this substitution confers resistance to APP, CHD, and PPZ herbicides in P. minor from Mexico. The mutations have been described previously only in a few cases; however, this is the first study reporting on a pattern of cross-resistance with these mutations in P. minor. The findings could be useful for better management of resistant biotypes carrying similar mutations.     

The role of K2O on sintering and crystallization of glass powder compacts in the Li2O–K2O–Al2O3–SiO2 system

The effects of K₂O content on sintering and crystallization of glass powder compacts in the Li₂O–K₂O–Al₂O₃–SiO₂ system were investigated. Glasses featuring SiO₂/Li₂O molar ratios of 2.69–3.13, far beyond the lithium disilicate (LD-Li₂Si₂O₅) stoichiometry, were produced by conventional melt-quenching technique. The sintering and crystallization behaviour of glass powders was explored using hot stage microscopy (HSM), scanning electron microscopy (SEM), differential thermal (DTA) and X-ray diffraction (XRD) analyses. Increasing K₂O content at the expense of SiO₂ was shown to lower the temperature of maximum shrinkage, eventually resulting in early densification of the glass-powder compacts. Lithium metasilicate was the main crystalline phase formed upon heat treating the glass powders with higher amounts of K₂O. In contrast, lithium disilicate predominantly crystallized from the compositions with lower K₂O contents resulting in strong glass–ceramics with high chemical and electrical resistance. The total content of K₂O should be kept below 4.63 mol% for obtaining LD-based glass–ceramics.     

Influence of the growth conditions on the defect density of single-walled carbon nanotubes

The influence of the temperature and precursor pressure on the defect density of single-walled carbon nanotubes (SWCNTs) grown by catalytic chemical vapor deposition was studied for several catalyst–precursor couples. The SWCNT defect density was assessed by studying the Raman D band. In situ Raman monitoring was used to determine experimental conditions allowing the preparation of samples free of pyrolytic carbon and not altered by air exposure. The most striking feature is that the Arrhenius plots of the I_G/I_D ratio systematically display a convex shape, i.e. the apparent activation energy decreases with increasing temperature. From HRTEM observations and oxidation experiments, this evolution of the D band features is ascribed to the catalytic growth of long SWCNTs with few defects at high temperature and of short and defective SWCNTs and carbon structures at low temperature. The convex Arrhenius behavior is well accounted by two kinetic models: (i) a model considering a change of intermediate states as a function of the temperature (for instance due to a phase transition of the catalyst particle or a change of intermediate carbon species) and (ii) a model considering a high-temperature process of defect creation (for instance by reaction with reactive gas species).     

Design and synthesis of foam glasses from recycled materials

Recycling has emerged as an environmental key point due to the diminishing of natural resources and the generation of ever-increasing amounts of industrial solid wastes. Glass wastes are among the materials that attract great interest in the recycling concept. This work presents the results of foams production from four series of compositions. The first series comprises powders of a sodium-calcium-silicate sheet glass cullet as the main component, an alkali-earth aluminosilicate glass as an additive, and a reagent grade silicon carbide (SiC) powder as gassing agent. In the second series, the glass cullet was used in combination with fly ashes (FLA) as main components, while SiC waste from abrasive paper served as foaming agent. In the third and fourth series, carbonates (calcite and dolomite) were used for foaming powder mixtures composed of sheet glass cullet and FLA, and powdered cathode ray tube panel glasses, respectively. All the processing parameters, including the main components, the nature and content of foaming agents are shown to play a crucial role on the foaming ability and final properties of the glass foams.     

Synthesis and structure-activity relationship of the isoindolinyl benzisoxazolpiperidines as potent,selective, and orally active human dopamine D4 receptor antagonists

A new class of potent dopamine D(4) antagonists was discovered with selectivity over dopamine D(2) and the alpha-1 adrenoceptor. The lead compound was discovered by screening our compound collection. The structure-activity relationships of substituted isoindoline rings and the chirality about the hydroxymethyl side chain were explored. The isoindoline analogues showed modest differences in potency and selectivity. The S enantiomer proved to be the more potent enantiomer at the D(4) receptor. Several analogues with greater than 100-fold selectivity for D(4) over D(2) and the alpha-1 adrenoreceptor were discovered. Several selective analogues were active in vivo upon oral or intraperitoneal administration. A chiral synthesis starting from either D- or L-O-benzylserine is also described.