Montmorillonite Exfoliation in LLDPE and Factors Affecting Its Orientation: From Monolayer to Multi-Nano-Layer Polymer Films.

The motivations of the present work are to investigate the exfoliation of montmorillonite within a linear low-density polyethylene matrix and to control its orientation during the cast extrusion process. The first part is focused on the exfoliation of the montmorillonite through the melt extrusion process. The accuracy and relevance of each method used to determine the exfoliation state of montmorillonite have been examined, thanks to X-ray diffraction, transmission electronic microscopy, and rheology. All these methods have presented limitations, but the combination of all leads to a better estimation of the exfoliation state. Finally, the orientation of the montmorillonite is quantified systematically by X-ray texture analysis and correlated with process parameters to discern which one is affecting their orientation. The results have demonstrated an enhancement of the "in-plane" orientation of the montmorillonite with the exfoliation, especially at high concentration and when combined with cast extrusion. Finally, in the multi-nano-layer polymer film configuration, the reduction of the individual layers 29 nm thickness leads to some orientation improvements. However, these improvements are almost at the same level as the concentration effect in a monolayer system. This work gives an overview of all the parameters needed to achieve a significant organo-modified montmorillonite "in-plane" orientation.

A Journey from Processing to Recycling of Multilayer Waste Films: A Review of Main Challenges and Prospects.

In a circular economy context with the dual problems of depletion of natural resources and the environmental impact of a growing volume of wastes, it is of great importance to focus on the recycling process of multilayered plastic films. This review is dedicated first to the general concepts and summary of plastic waste management in general, making emphasis on the multilayer films recycling process. Then, in the second part, the focus is dealing with multilayer films manufacturing process, including the most common materials used for agricultural applications, their processing, and the challenges of their recycling, recyclability, and reuse. Hitherto, some prospects are discussed from eco-design to mechanical or chemical recycling approaches.

Multi-Micro/Nanolayer Films Based on Polyolefins: New Approaches from Eco-Design to Recycling.

This paper describes a future-oriented approach for the valorization of polyethylene-based multilayer films. The method involves going from eco-design to mechanical recycling of multilayer films via forced assembly coextrusion. The originality of this study consists in limiting the number of constituents, reducing/controlling the thickness of the layers and avoiding the use of tie layers. The ultimate goal is to improve the manufacturing of new products from recycled multilayer materials by simplifying their recyclability. Within this framework, new structures were developed with two polymer systems: polyethylene/polypropylene and polyethylene/polystyrene, with nominal micro- and nanometric thicknesses. Hitherto, the effect of the multi-micro/nanolayer architecture as well as initial morphological and mechanical properties was evaluated. Several recycling processes were investigated, including steps such as: (i) grinding; (ii) monolayer cast film extrusion; or (iii) injection molding with or without an intermediate blending step by twin-screw extrusion. Subsequently, the induced morphological and mechanical properties were investigated depending on the recycling systems and the relationships between the chosen recycling processes or strategies, and structure and property control of the recycled systems was established accordingly. Based on the results obtained, a proof of concept was demonstrated with the eco-design of multi-micro/nanolayer films as a very promising solution for the industrial issues that arise with the valorization of recycled materials.

In vitro and in vivo pharmacology of NXT629, a novel and selective PPARα antagonist.

Peroxisome-proliferator activated receptors (PPAR) are members of the nuclear hormone receptor superfamily which regulate gene transcription. PPARα is a key regulator of lipid homeostasis and a negative regulator of inflammation. Under conditions of metabolic stress such as fasting or glucose deprivation, PPARα is upregulated in order to control gene expression necessary for processing alternate fuel sources (e.g. fatty acid oxidation) and thereby promote maintenance of cell viability. Clinically, PPARα expression is upregulated in diseased tissues such as melanoma, chronic lymphocytic leukemia, ovarian and prostate cancer. This may allow for cellular proliferation and metastasis. Importantly, genetic knockouts of PPARα have been shown to be protected against tumor growth in a variety of syngeneic tumors models. We hypothesized that a potent and selective PPARα antagonist could represent a novel cancer therapy. Early in our discovery research, we identified NXT629 (Bravo et al., 2014). Herein we describe the pharmacology of NXT629 and demonstrate that it is a potent and selective PPARα antagonist. We identify NXT629 as a valuable tool for use in in vivo assessment of PPARα due to its good systemic exposure following intraperitoneal injection. We explore the in vivo pharmacology of NXT629 and demonstrate that it is efficacious in pharmacodynamic models that are driven by PPARα. Finally, we probe the efficacy of NXT629 in disease models where PPARα knockouts have shown to be protected. We believe that PPARα antagonists will be beneficial in diseases such as ovarian cancer and melanoma where PPARα and fatty acid oxidation may be involved.

A Selective Novel Peroxisome Proliferator-Activated Receptor (PPAR)-α Antagonist Induces Apoptosis and Inhibits Proliferation of CLL Cells In Vitro and In Vivo.

Tumor-specific metabolic changes can reveal new therapeutic targets. Our findings implicate a supporting role for fatty acid metabolism in chronic lymphocytic leukemia (CLL) cell survival. Peroxisome proliferator-activated receptor (PPAR)-α, a major transcriptional regulator of fatty acid oxidation, was recently shown to be upregulated in CLL. To evaluate PPARα as a potential therapeutic target, we developed a highly selective, potent small molecule antagonist of PPARα, NXT629. NXT629 inhibited agonist-induced transcription of PPARα-regulated genes, demonstrating target engagement in CLL cells. Furthermore, NXT629 induced apoptosis of CLL cells even in the presence of a protective microenvironment. To mimic the proliferative lymphoid compartment of CLL, we examined the activity of NXT629 on CLL cells that were stimulated to proliferate in vitro. NXT629 reduced the number of leukemia cells undergoing cell division. In addition, in two xenograft mouse models of CLL (one a model for nondividing and one for dividing CLL), NXT629 reduced the number of viable CLL cells in vivo. Overall, these results suggest that fatty acid metabolism promotes survival and proliferation of primary CLL cells and that inhibiting PPARα gene regulation could be a new therapeutic approach to treating CLL.

Hippocampal cell alterations induced by the inhalation of vanadium pentoxide (V(2)O(5)) promote memory deterioration.

Spatial memory may be severely impaired as a consequence of ageing and neurodegenerative diseases, conditions that include neuronal damage. Vanadium (V) is a metalloid widely distributed in the environment and exerts severe toxic effects on a wide variety of biological systems. Reports about V inhalation toxicity on the CNS are limited, thus the purpose of this study is to determine the effects of Vanadium pentoxide (V(2)O(5)) inhalation (0.02M) on the memory and its correlation with the cytology of the hippocampus CA1. Forty eight CD-1 male mice were trained in spatial memory tasks and inhaled 1h twice a week; after each inhalation animals were evaluated and sacrificed from 1 to 4 weeks, perfused and processed for Golgi method and for ultrastructure evaluation. The cytological analysis consisted in counting the number of dendritic spines of 20 pyramidal neurons of hippocampus CA1, as well as ultrastructural characteristics. Results show that V inhalation produces a time dependent loss of dendritic spines, necrotic-like cell death, and notorious alterations of the hippocampus CA1 neuropile, which correlate with spatial memory impairment. Our data suggest that V induces important cellular and functional alterations, fact that deserves special attention since the concentration's trend of this element in the atmosphere is increasing.

Ultrastructural modifications in the mitochondrion of mouse Sertoli cells after inhalation of lead, cadmium or lead-cadmium mixture.

CD-1 mice inhaled 0.01 M lead acetate, 0.006 M cadmium chloride or Pb-Cd mixture during 1h twice a week during 4 weeks. Testes were processed for transmission electron microscopic analysis. The percentage of damaged mitochondria was related to exposure time and the type of metal inhaled, noticing more damage when the mixture was administered. A dose-time relationship was found. Cadmium chloride caused the most severe mitochondrial alteration compared to lead acetate, whereas the mixture was more aggressive compared with each metal alone. Our results suggest that the changes in Sertoli cell could lead to a transformation process that may interfere with spermatogenesis.

Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor.

Through a multiplex promoter spanning 218 kb, the phase II UDP-glucuronosyltransferase 1A (UGT1) gene encodes at least eight differently regulated mRNAs whose protein products function as the principal means to eliminate a vast array of steroids, heme metabolites, environmental toxins, and drugs. The orphan nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) were originally identified as sensors able to respond to numerous environmentally derived foreign compounds (xenobiotics) to promote detoxification by phase I cytochrome P450 genes. In this report, we show that both receptors can induce specific UGT1A isoforms including those involved in estrogen, thyroxin, bilirubin, and carcinogen metabolism. Transgenic mice expressing a constitutively active form of human PXR show markedly increased UGT activity toward steroid, heme, and carcinogens, enhanced bilirubin clearance, as well as massively increased steroid clearance. The ability of PXR and constitutive androstane receptor and their ligands to transduce both the phase I and phase II adaptive hepatic response defines a unique transcriptional interface that bridges the ingestion and metabolism of environmental compounds to body physiology.