Acid Value,Polar Compounds and Polymers as Determinants of the Efficient Conversion of Waste Frying Oils to Biodiesel

The cost of starting materials for the production of biodiesel is typically 75 % of the final retail price. Oils previously used for frying, waste frying oils (WFO), are a very suitable resource. Repetitive use of oil for frying foods involves high temperature, moisture and aeration for extended periods. The most important deterioration processes triggered by these conditions are hydrolysis and oxidation. In this study, 24 WFO samples of different origins were analyzed and classified as potential starting materials for biodiesel production using three quality parameters representing the main factors that affect the conversion of WFO. These parameters were: acid value, content of polar compounds and content of polymers, which varied in the ranges from 0.2 to 7.6, 14.9 to 43.2 and 0.9 to 15.2 %, respectively. Ester content obtained using conventional transesterification (TE) for WFO conversion decreased with increased levels of WFO deterioration determined by any of the three parameters noted above. TE products obtained had ester content between 81.4 and 95.7 %. Total ester content of a WFO sample with relatively low %AV could be increased to 96.5 % using a two-stage base catalysis TE. Finally, conversion of WFO samples resulted in ester contents of 89.0 and 91.3 %, respectively, when transesterified by conventional TE. After blending up to 10 % with refined oil, the ester content achieved was near 96.5 %. Thus, the blending represents an alternative for obtaining a product with suitable ester content.     

Thermal Analysis of Charcoal from Fast-Growing Eucalypt Wood: Influence of Raw Material Moisture Content

This study aimed to investigate the influence of raw material moisture content on the properties of charcoal from fast-growing Eucalyptus benthamii wood. For that, three treatments were performed with 0, 30, and 50% in relation to the wet basis moisture of the wood samples. The carbonization process used an electric kiln with a heating rate of 1.60°C min^?1, initial temperature of 25 to 600°C at the end, kept constant at that temperature for two hours. Variables were statistically analyzed for charcoal yield, non-condensable gases, liquor, and fixed carbon and properties: fixed carbon content, volatile, ash, bulk density, and moisture content of charcoal. According to the results, the charcoal produced from dry wood presented the highest properties, yet the charcoal produced from wood with 30% moisture content showed similar properties.     

Role of strain induced crystallization and oxidative crosslinking in fracture properties of rubbers

Tensile properties and crack propagation properties, especially critical strain energy release rate in mode I, G_IC, have been used to investigate fracture properties of elastomers and their relationships with microstructure. These investigations were mainly based on a series of comparisons: first, the behaviour of polychloroprene rubber (CR), undergoing stress hardening due to strain induced crystallization (SIC) and oxidative crosslinking (OCL) was compared with that of chlorinated polyethylene (CPE), which undergoes SIC but not OCL, and with a polyurethane based on hydroxyl terminated polybutadiene (PU) which undergoes OCL but not SIC. Comparisons were also made on CR between fracture behaviour at ambient temperature, where SIC occurs and at 100 °C where there is no SIC. Finally, oxidative crosslinking was used to vary in a continuous way the crosslink density in CR and PU, in order to evaluate the role of crosslinking in fracture behaviour.     

Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib,Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.     

Structural Plasticity Is a Feature of Rheostat Positions in the Human Na+/Taurocholate Cotransporting Polypeptide (NTCP)

In the Na⁺/taurocholate cotransporting polypeptide (NTCP), the clinically relevant S267F polymorphism occurs at a “rheostat position”. That is, amino acid substitutions at this position (“S267X”) lead to a wide range of functional outcomes. This result was particularly striking because molecular models predicted the S267X side chains are buried, and thus, usually expected to be less tolerant of substitutions. To assess whether structural tolerance to buried substitutions is widespread in NTCP, here we used Rosetta to model all 19 potential substitutions at another 13 buried positions. Again, only subtle changes in the calculated stabilities and structures were predicted. Calculations were experimentally validated for 19 variants at codon 271 (“N271X”). Results showed near wildtype expression and rheostatic modulation of substrate transport, implicating N271 as a rheostat position. Notably, each N271X substitution showed a similar effect on the transport of three different substrates and thus did not alter substrate specificity. This differs from S267X, which altered both transport kinetics and specificity. As both transport and specificity may change during protein evolution, the recognition of such rheostat positions may be important for evolutionary studies. We further propose that the presence of rheostat positions is facilitated by local plasticity within the protein structure. Finally, we note that identifying rheostat positions may advance efforts to predict new biomedically relevant missense variants in NTCP and other membrane transport proteins.     

From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl₂ or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.     

Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients

Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient’s plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ.     

Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception

The avoidance of being overweight or obese is a daily challenge for a growing number of people. The growing proportion of people suffering from a nutritional imbalance in many parts of the world exemplifies this challenge and emphasizes the need for a better understanding of the mechanisms that regulate nutritional balance. Until recently, research on the central regulation of food intake primarily focused on neuronal signaling, with little attention paid to the role of glial cells. Over the last few decades, our understanding of glial cells has changed dramatically. These cells are increasingly regarded as important neuronal partners, contributing not just to cerebral homeostasis, but also to cerebral signaling. Our understanding of the central regulation of energy balance is part of this (r)evolution. Evidence is accumulating that glial cells play a dynamic role in the modulation of energy balance. In the present review, we summarize recent data indicating that the multifaceted glial compartment of the brainstem dorsal vagal complex (DVC) should be considered in research aimed at identifying feeding-related processes operating at this level.     

Colloidal thiophosphorus calcium salt as antiwear additive

This paper describes the synthesis of an oil-soluble colloidal calcium thiophosphate by a direct route. It consists of the reaction of calcium oxide or hydroxide with tetraphosphorus decasulphide and water in the presence of a surfactant such as a calcium alkylaryl sulphonate in an organic medium. Reaction and micellisation occurred simultaneously according to a one-step process. The product is characterised by a high calcium, phosphorus and sulphur content. The colloidal nature of the product has been confirmed by dialysis. The ³¹P-NMR spectrum showed signals characteristic of a blend of different calcium thiophosphates, plus calcium phosphate. The product could be defined as a core of different calcium (thio)phosphates surrounded by a calcium alkylaryl sulphonate shell, according to a reverse micelle type association in oil. This compound was evaluated as an antiwear additive in a 130 Neutral Solvent mineral oil by anti-wear and extreme-pressure four-ball tests. The extreme-pressure characteristics depend on the concentration of mineral colloidal core in oil. The antiwear properties are a function not only of the concentration, but also of the colloidal core/surfactant shell ratio. Thermogravimetric analysis of these colloidal species shows a weight loss in the 350°C to 450°C range, due to surfactant degradation. The further evolution of weight loss up to 900°C demonstrates the high thermal stability of the colloidal calcium (thio)phosphate core.     

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.