Soil remediation by an advanced oxidative method assisted with ultrasonic energy

A new process for the remediation of soil contaminated with hydrocarbons is proposed. The innovation consists on coupling an advanced oxidative method, using a Fenton-type catalyst, with the application of ultrasonic energy. The use of ultrasonic energy not only assists the desorption of the contaminants from the soil, but also promotes the formation of OH radicals, which are the oxidant agents involved in the oxidation process. Different Fenton-like catalysts were employed in the present study; however, the highest removal of toluene and xylenes were obtained with iron sulfate and copper sulfate, respectively. Also, hydrogen peroxide was tested at different concentrations, and it was found that increasing its concentration enhanced the removal of all the contaminants. Finally, it was demonstrated that applying ultrasonic energy to the reacting system process noticeably enhanced the global efficiency of the process due to a synergistic effect in conjunction with the hydrogen peroxide concentration and type of catalyst.     

Pharmacogenetics in Neuroblastoma: What Can Already Be Clinically Implemented and What Is Coming Next?

Pharmacogenetics is one of the cornerstones of Personalized Precision Medicine that needs to be implemented in the routine of our patients’ clinical management in order to tailor their therapies as much as possible, with the aim of maximizing efficacy and minimizing toxicity. This is of great importance, especially in pediatric cancer and even more in complex malignancies such as neuroblastoma, where the rates of therapeutic success are still below those of many other types of tumors. The studies are mainly focused on germline genetic variants and in the present review, state of the art is presented: which are the variants that have a level of evidence high enough to be implemented in the clinic, and how to distinguish them from the ones that still need validation to confirm their utility. Further aspects as relevant characteristics regarding ontogeny and future directions in the research will also be discussed.     

Conjugated linoleic acid supplementation in humans: Effects on circulating leptin concentrations and appetite

Conjugated linoleic acid (CLA) has been demonstrated to reduce body fat in animals. However, the mechanism by which this reduction occurs is unknown. Leptin may mediate the effect of CLA to decrease body fat. We assessed the effects of 64 d of CLA supplementation (3 g/d) on circulating leptin, insulin, glucose, and lactate concentrations in healthy women. Appetite was assessed as a physiological correlate of changes in circulating leptin levels. Analysis of plasma leptin concentrations adjusted for adiposity by using fat mass as a covariate showed that CLA supplementation significantly decreased circulating leptin concentrations in the absence of any changes of fat mass. Mean leptin levels decreased over the first 7 wk and then returned to baseline levels over the last 2 wk of the study in the CLA-treated group. Appetite parameters measured at around the time when the greatest decreases in leptin levels were observed showed no significant differences between supplementation and baseline determinations in the CLA-supplemented group or between the CLA and placebo-supplemented groups. There was a nonsignificant trend for mean insulin levels to increase toward the end of the supplementation period in CLA-treated subjects. CLA did not affect plasma glucose and lactate over the treatment period. Thus, 64 d of CLA supplementation in women produced a transient decrease in leptin levels but did not alter appetite. CLA did not affect these parameters in a manner that promoted decreases of adiposity.     

Murphree and vaporization efficiencies in multicomponent distillation

A quantitative comparison between Murphree and vaporization efficiencies is presented based on ternary distillation data for the systems acetone/methanol/ethanol, acetone/benzene/chlorobenzene, benzene/toluene/mxylene and n-hexane/methylcyclopentane/benzene. The influence of experimental errors on calculated values of Murphree efficiencies is also analysed.It is shown that the vaporization efficiency model fails to describe the behaviour of distillation plates and it is suggested that Murphree's model gives a more useful representation of the behaviour of distillation columns.     

Oxidation in fish lipids during thermal stress as studied by 13C nuclear magnetic resonance spectroscopy

¹³C Nuclear magnetic resonance spectroscopy has been applied to elucidate the mechanism of lipid oxidation occurring during thermal treatment of fish. Effects of temperature and time of processing have been studied by means of a model system of lipids, extracted from salmon (Salmo salar) muscle, to simulate industrial conditions of canning. Unsaturated fatty acids located at the sn-2 position of the glycerol moiety were the most prone to oxidative damage. Regarding the mechanism of the reaction, results inferred from olefinic and methylenic resonances indicated a higher susceptibility of the allylic sites closest to the carbonyl group, followed by those placed near the methyl terminal group. Unsaturations located in the middle of the carbon chain did not show much damage. The glyceryl region provided an unusual resonance at 53.4 ppm, which could be assigned to a hydroxylic compound formed during process.     

New Insights into the Determinants of Specificity in Human Type I Arginase: Generation of a Mutant That Is Only Active with Agmatine as Substrate

Arginase catalyzes the hydrolysis of L-arginine into L-ornithine and urea. This enzyme has several analogies with agmatinase, which catalyzes the hydrolysis of agmatine into putrescine and urea. However, this contrasts with the highlighted specificity that each one presents for their respective substrate. A comparison of available crystal structures for arginases reveals an important difference in the extension of two loops located in the entrance of the active site. The first, denominated loop A (I129-L140) contains the residues that interact with the alpha carboxyl group or arginine of arginase, and the loop B (D181-P184) contains the residues that interact with the alpha amino group of arginine. In this work, to determine the importance of these loops in the specificity of arginase, single, double, and triple arginase mutants in these loops were constructed, as well as chimeras between type I human arginase and E. coli agmatinase. In previous studies, the substitution of N130D in arginase (in loop A) generated a species capable of hydrolyzing arginine and agmatine. Now, the specificity of arginase is completely altered, generating a chimeric species that is only active with agmatine as a substrate, by substituting I129T, N130Y, and T131A together with the elimination of residues P132, L133, and T134. In addition, Quantum Mechanic/Molecular Mechanic (QM/MM) calculations were carried out to study the accommodation of the substrates in in the active site of this chimera. With these results it is concluded that this loop is decisive to discriminate the type of substrate susceptible to be hydrolyzed by arginase. Evidence was also obtained to define the loop B as a structural determinant for substrate affinity. Concretely, the double mutation D181T and V182E generate an enzyme with an essentially unaltered k_cat value, but with a significantly increased K_m value for arginine and a significant decrease in affinity for its product ornithine.     

Immune Checkpoint Blockade via PD-L1 Potentiates More CD28-Based than 4-1BB-Based Anti-Carbonic Anhydrase IX Chimeric Antigen Receptor T Cells

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to ≅10⁸ CAR T cells/kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here, we tested CD8α/4-1BB compared to CD28-based anti-CAIX CAR peripheral blood mononuclear cells (PBMCs) releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo. Using a ≅10⁷ CAR PBMCs cells/kg dose, anti-CAIX CD28 CAR T cells releasing anti-PD-L1 IgG highly decrease both tumor volume and weight in vivo, avoiding the occurrence of metastasis. This antitumoral superiority of CD28-based CAR PBMCs cells compared to 4-1BB occurred under ICB via PD-L1. Furthermore, the T cell exhaustion status in peripheral CD4 T cells, additionally to CD8, was critical for CAR T cells efficiency. The lack of hepatotoxicity and nephrotoxicity upon the administration of a 10⁷ CAR PMBCs cells/kg dose is the basis for carrying out clinical trials using anti-CAIX CD28 CAR PBMCs cells releasing anti-PD-L1 antibodies or anti-CAIX 4-1BB CAR T cells, offering exciting new prospects for the treatment of refractory ccRCC and hypoxic tumors.