Gold nanoparticles supported on functionalized silica as catalysts for alkyne hydroamination: A chemico-physical insight

Highly stable gold nanoparticles anchored on propynylcarbamate-functionalized silica (Au/SiO2@Yne) have been efficiently utilized for the heterogeneous hydroamination of phenylacetylene with aniline under different reaction conditions. In order to ascertain the eventual influence of surface silanol groups on the system activity and selectivity tailored modifications of Au/SiO2@Yne catalysts were pursued according to two different strategies, involving respectively functionalization with trimethylethoxysilane (Au/SiO2@Yne-TMS) or post-treatment with triethylamine (Au/SiO2@Yne-NEt3). The prepared materials were analysed by several complementary techniques such as Solid State NMR (SS NMR), Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectroscopy (XPS), X-ray Diffraction (XRD). A comparison of the resulting catalytic activities with that of the pristine Au/SiO2@Yne revealed a significant improvement for Au/SiO2@Yne-NEt3 in terms of both conversion and selectivity. Recycling and stability studies showed a catalytic activity decrease after the first run, due to the formation of polyphenylacetylene (PPhA) oligomers shielding the active sites. PPhA removal by sonication in acetone fully restored the catalytic activity and empowered the system with a good operational stability, a very crucial issue in view of eventual practical applications

PRC2 is dispensable for HOTAIR-mediated transcriptional repression

Long non-coding RNAs (lncRNAs) play diverse roles in physiological and pathological processes. Several lncRNAs have been suggested to modulate gene expression by guiding chromatin-modifying complexes to specific sites in the genome. However, besides the example of Xist, clear-cut evidence demonstrating this novel mode of regulation remains sparse. Here, we focus on HOTAIR, a lncRNA that is overexpressed in several tumor types and previously proposed to play a key role in gene silencing through direct recruitment of Polycomb Repressive Complex 2 (PRC2) to defined genomic loci. Using genetic tools and a novel RNA-tethering system, we investigated the interplay between HOTAIR and PRC2 in gene silencing. Surprisingly, we observed that forced overexpression of HOTAIR in breast cancer cells leads to subtle transcriptomic changes that appear to be independent of PRC2. Mechanistically, we found that artificial tethering of HOTAIR to chromatin causes transcriptional repression, but that this effect does not require PRC2. Instead, PRC2 recruitment appears to be a consequence of gene silencing. We propose that PRC2 binding to RNA might serve functions other than chromatin targeting

Evolution of enhanced innate immune evasion by SARS-CoV-2

Emergence of SARS-CoV-2 variants of concern (VOCs) suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on characterisation of spike changes in VOCs, mutations outside spike likely contribute to adaptation. Here we used unbiased abundance proteomics, phosphoproteomics, RNAseq and viral replication assays to show that isolates of the Alpha (B.1.1.7) variant3 more effectively suppress innate immune responses in airway epithelial cells, compared to first wave isolates. We found that Alpha has dramatically increased subgenomic RNA and protein levels of N, Orf9b and Orf6, all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful Alpha transmission, and may increase in vivo replication and duration of infection4. The importance of mutations outside Spike in adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the Delta and Omicron N/Orf9b regulatory regions

Polyaniline/poly (2-acrylamido-2-methyl-1-propanesulfonic acid) modified cellulose as promising material for sensors design

A material based on cellulose coated with polyaniline/poly (2-acrylamido-2-methyl-1-propanesulfonic acid) (Cell/PANI-PAMPSA) was synthesized in a simple way starting from cellulose fibres, aniline and using PAMPSA as dopant. The morphology, mechanical properties, thermal stability, and electrical conductivity were investigated by means of several complementary techniques. The obtained results highlight the excellent features of the Cell/PANI-PAMPSA composite with respect to the Cell/PANI one. Based on the promising performance of this material, novel device functions and wearable applications have been tested. We focused on its possible single use as: i) humidity sensors and ii) disposable biomedical sensors to provide immediate diagnostic services as close to the patient as possible for heart rate or respiration activity monitoring. To our knowledge, this is the first time that Cell/PANI-PAMPSA system has been used for such applications

Magnetic composite materials for energy storage applications

In this work the development of flexible graphite electrodes suitably modified for their use in the preparation of pseudocapacitors is investigated. The optimal conditions for the electrosynthesis of nanocomposite films consisting of polyanaline (PANI, a conductive polymer)[1] and nanoparticles based on bare and/or functionalized magnetite and gold are studied. In particular, magnetite and Au/magnetite nanoparticles labelled as Au/Fe3O4 and Au/Fe3O4@Yne (Yne = propynylcarbamate)[2,3,4], are used to obtain modified PANI electrodes with improved performance in respect of pristine PANI in terms of charge density, surface area and storage capacity. The electrosynthesis of the polymer and polymer-composites is carried out through cyclic voltammetry, in aqueous solution. The electrodes are characterized by CV, SEM, charge-discharge test (C/D) and impedance test (EIS). Finally, the best performing electrodes are used to assemble a symmetrical supercapacitor

Mechanosensor YAP cooperates with TGF-β1 signaling to promote myofibroblast activation and matrix stiffening in a 3D model of human cardiac fibrosis

: Cardiac fibrosis is characterized by a maladaptive remodeling of the myocardium, which is controlled by various inflammatory pathways and cytokines. This remodeling is accompanied by a significant stiffening of the matrix, which may contribute to further activate collagen synthesis and scar formation. Evidence suggests that TGF-β1 signaling, the main pro-fibrotic pathway in cardiac fibrosis, might cooperates with the Hippo transcriptional pathway by activating YAP. To directly test the cooperation of mechanical cues and paracrine signaling in cardiac fibrosis, we developed a 3D model of cardiac extracellular matrix remodeling by generating tissue blocks with Gelatin Methacrylate, a bioink with tunable stiffness, and human cardiosphere-derived stromal cells. Using this strategy, we assessed the cooperation of TGF-β1 and YAP transcriptional factor to matrix compaction. Using mechanical compression tests, Masson's trichrome staining, immunofluorescence, and RT-qPCR, we demonstrate that pharmacological inhibition of YAP complex reverts almost completely the pro-compaction phenotype and the matrix-remodeling activity of cells treated with TGF-β1. Our data show a direct connection between the classical pro-fibrotic signaling driven by TGF-β1 and the mechanically activated pathways under the control of YAP in cardiac remodeling. Treatment with the elective drug targeting YAP is sufficient to override this cooperation with potential benefits for anti-fibrotic therapeutic applications. STATEMENT OF SIGNIFICANCE: Heart failure is a pathology in continuous growth worldwide, characterized by a progressive fibrosis, which decreases the pumping efficiency of the heart. Experimental evidences suggest that fibroblasts, normally responsible for the turnover of the cardiac matrix, are involved in myocardial fibrosis by differentiating into 'myofibroblasts'. These cells remodel extensively the cardiac extracellular matrix and deposit abundant collagen with a consequent increase in stiffness. In the present contribution, we propose a new 3D model of cell-mediated cardiac extracellular matrix stiffening to investigate the mechano-chemical mechanisms underlying the onset of the pathology. We also consolidate a pharmacological treatment able to prevent the pathological activation of fibroblasts with potential benefits for anti-fibrotic treatment of the failing heart