Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments.     

Water-Based Graphene Oxide–Silicon Hybrid Nanofluids—Experimental and Theoretical Approach

In the current paper, a new hybrid nanofluid based on graphene oxide sheets and silicon nanoparticles is proposed for thermal applications. GO sheets and Si nanoparticles with different mixture ratios are dispersed in distilled water. Dynamic viscosity is measured at temperatures within the range 20–50 °C and the values are compared to the results available in the literature. The results indicated that the viscosity increases with increasing the mixture ratio of graphene oxide. A new correlation for the dynamic viscosity based on the experimental findings is proposed. Finally, the criteria for the performance of new hybrid nanofluid for thermal applications are analyzed.     

New Poly(N-isopropylacrylamide-butylacrylate) Copolymer Biointerfaces and Their Characteristic Influence on Cell Behavior In Vitro

Designing and obtaining new synthetic smart biointerfaces with specific and controlled characteristics relevant for applications in biomedical and bioengineering domains represents one of the main challenges in these fields. In this work, Matrix-Assisted Pulsed Laser Evaporation (MAPLE) is used to obtain synthetic biointerfaces of poly(N-isopropyl acrylamide-butyl acrylate) p(NIPAM-BA) copolymer with different characteristics (i.e., roughness, porosity, wettability), and their effect on normal HEK 293 T and murine melanoma B16-F1 cells is studied. For this, the influence of various solvents (chloroform, dimethylsulfoxide, water) and fluence variation (250–450 mJ/cm²) on the morphological, roughness, wettability, and physico–chemical characteristics of the coatings are evaluated by atomic force microscopy, scanning electron microscopy, contact angle measurements, Fourier-transform-IR spectroscopy, and X-ray photoelectron spectroscopy. Coatings obtained by the spin coating method are used for reference. No significant alteration in the chemistry of the surfaces is observed for the coatings obtained by both methods. All p(NIPAM-BA) coatings show hydrophilic character, with the exception of those obtained with chloroform at 250 mJ/cm². The surface morphology is shown to depend on both solvent type and laser fluence and it ranges from smooth surfaces to rough and porous ones. Physico–chemical and biological analysis reveal that the MAPLE deposition method with fluences of 350–450 mJ/cm² when using DMSO solvent is more appropriate for bioengineering applications due to the surface characteristics (i.e., pore presence) and to the good compatibility with normal cells and cytotoxicity against melanoma cells.     

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.     

Fusarium graminearum Infection Strategy in Wheat Involves a Highly Conserved Genetic Program That Controls the Expression of a Core Effectome

Fusarium graminearum, the main causal agent of Fusarium Head Blight (FHB), is one of the most damaging pathogens in wheat. Because of the complex organization of wheat resistance to FHB, this pathosystem represents a relevant model to elucidate the molecular mechanisms underlying plant susceptibility and to identify their main drivers, the pathogen’s effectors. Although the F. graminearum catalog of effectors has been well characterized at the genome scale, in planta studies are needed to confirm their effective accumulation in host tissues and to identify their role during the infection process. Taking advantage of the genetic variability from both species, a RNAseq-based profiling of gene expression was performed during an infection time course using an aggressive F. graminearum strain facing five wheat cultivars of contrasting susceptibility as well as using three strains of contrasting aggressiveness infecting a single susceptible host. Genes coding for secreted proteins and exhibiting significant expression changes along infection progress were selected to identify the effector gene candidates. During its interaction with the five wheat cultivars, 476 effector genes were expressed by the aggressive strain, among which 91% were found in all the infected hosts. Considering three different strains infecting a single susceptible host, 761 effector genes were identified, among which 90% were systematically expressed in the three strains. We revealed a robust F. graminearum core effectome of 357 genes expressed in all the hosts and by all the strains that exhibited conserved expression patterns over time. Several wheat compartments were predicted to be targeted by these putative effectors including apoplast, nucleus, chloroplast and mitochondria. Taken together, our results shed light on a highly conserved parasite strategy. They led to the identification of reliable key fungal genes putatively involved in wheat susceptibility to F. graminearum, and provided valuable information about their putative targets.     

Nanoparticle evolution in flame spray pyrolysis—Process design via experimental and computational analysis

In flame spray pyrolysis (FSP), the evolution of metal oxide nanoparticles relies on quite a number of droplet (liquid) and vapor phase related physical mechanism as for instance precursor evaporation, oxidation, nucleation via gas-to-particle conversion mechanism, and subsequent particle (solid) growth mechanisms based on coagulation, sintering/coalescence, and agglomeration. The liquid precursor and dispersion oxygen feed rates are relevant control parameters of the FSP process for tailoring the nanoparticle size (diameter) and structure as well as the atomizer nozzle configuration. Sophisticated nonintrusive, laser-based in situ and ex situ diagnostics with multiscale spatial resolution (micrometer to meter range) are applied for analyzing droplet formation and size, gas velocity, temperature, species concentration, as well as primary and agglomerate diameters along the flow direction. Computational fluid dynamics (CFD) are coupled with population balance modeling (PBM) to elucidate the nanoparticle dynamics within the reactive spray. It is found that the CFD-PBM approach allows estimations of primary and agglomerate nanoparticle diameters within 80 and 75% accuracy compared to experimental data, suggesting that the methods presented could pave the way for designing next-generations of flame reactors.     

Ag2O–Al2O3–ZrO2 Trimetallic Nanocatalyst for High Performance Photodegradation of Nicosulfuron Herbicide

Topics in Catalysis - In the present study, Ag2O–Al2O3–ZrO2 based trimetallic oxide nanocatalyst was designed using simple microwave assisted reduction method. It was characterized...     

Biosynthetic Plasticity Enables Production of Fluorinated Aurachins

Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explored the plasticity of the aurachin biosynthesis pathway with regard to using fluoro- and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics. The incorporation rates of the tested precursor molecules disclosed a regiopreference for halogen substitution as well as steric limitations of enzymatic substrate tolerance. Three previously undescribed fluorinated aurachin derivatives were produced in preparative amounts by fermentation and structurally characterized. Furthermore, their antibacterial activities were evaluated in comparison to their natural congener aurachin D.