Putative Circulating MicroRNAs Are Able to Identify Patients with Mitral Valve Prolapse and Severe Regurgitation

Mitral valve prolapse (MVP) associated with severe mitral regurgitation is a debilitating disease with no pharmacological therapies available. MicroRNAs (miRNA) represent an emerging class of circulating biomarkers that have never been evaluated in MVP human plasma. Our aim was to identify a possible miRNA signature that is able to discriminate MVP patients from healthy subjects (CTRL) and to shed light on the putative altered molecular pathways in MVP. We evaluated a plasma miRNA profile using Human MicroRNA Card A followed by real-time PCR validations. In addition, to assess the discriminative power of selected miRNAs, we implemented a machine learning analysis. MiRNA profiling and validations revealed that miR-140-3p, 150-5p, 210-3p, 451a, and 487a-3p were significantly upregulated in MVP, while miR-223-3p, 323a-3p, 340-5p, and 361-5p were significantly downregulated in MVP compared to CTRL (p ≤ 0.01). Functional analysis identified several biological processes possible linked to MVP. In addition, machine learning analysis correctly classified MVP patients from CTRL with high accuracy (0.93) and an area under the receiving operator characteristic curve (AUC) of 0.97. To the best of our knowledge, this is the first study performed on human plasma, showing a strong association between miRNAs and MVP. Thus, a circulating molecular signature could be used as a first-line, fast, and cheap screening tool for MVP identification.     

Tumor Necrosis Factor α and Interleukin-1β Acutely Inhibit AgRP Neurons in the Arcuate Nucleus of the Hypothalamus

Obesity-associated low-grade inflammation favors weight gain, whereas systemic infection frequently leads to anorexia. Thus, inflammatory signals can either induce positive or negative energy balance. In this study, we used whole-cell patch-clamp to investigate the acute effects of three important proinflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-6, and interleukin-1β (IL-1β) on the membrane excitability of agouti-related peptide (AgRP)- or proopiomelanocortin (POMC)-producing neurons. We found that both TNF-α and IL-1β acutely inhibited the activity of 35–42% of AgRP-producing neurons, whereas very few POMC neurons were depolarized by TNF-α. Interleukin-6 induced no acute changes in the activity of AgRP or POMC neurons. Our findings indicate that the effect of TNF-α and IL-1β, especially on the activity of AgRP-producing neurons, may contribute to inflammation-induced anorexia observed during acute inflammatory conditions.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Kinetics of Soybean Oil Hydrolysis on Niobium Catalysts

The catalytic hydrolysis of soybean oil was used as an alternative for the production of monoglycerides (MG) and diglycerides (DG). The reactions were conducted in a stainless-steel tubular reactor in the temperature range of 240–290 °C, on niobium phosphate (NBP) and niobium oxide (NBO) as catalysts. In the hydrolysis reactions at 270 °C, the maximum selectivities of the products of interest were obtained at 22 % MG and 48 % DG for the reaction with NBP, and 7 % MG and 33 % DG with NBO, for 59 % and 36 % of triglyceride conversion in 10 min, respectively. The proposed kinetic model presented a good fit of the theoretical model with the experimental data, showing that the previous hypotheses considered for the mechanism development are suitable for describing the kinetics of soybean oil hydrolysis.     

Restricted Participation on Financial Markets: A General Equilibrium Approach Using Variational Inequality Methods

Networks and Spatial Economics - We deal with the analysis of a general equilibrium model with restricted participation in financial markets and with numeraire assets. We consider an exchange...     

Evaluation of chlorite and chlorate genotoxicity using plant bioassays and in vitro DNA damage tests

In the last few years chlorine dioxide has been increasingly used for disinfecting drinking water in many countries. Although it does not react with humic substances, chlorine dioxide added to water is reduced primarily to chlorite and chlorate ions, compounds that are under investigation for their potential adverse effects on human health. The aim of this research was to study the genotoxicity of chlorite and chlorate and their mixtures. The end-points included two plant tests (chromosomal aberration test in Allium cepa and micronucleus assay in Tradescantia, carried out at different times of exposure) and two genotoxicity tests in human HepG2 cells (comet assay and cytokinesis-blocked micronucleus test). Preliminary toxicity tests were carried out for both plant and HepG2 assays. The results showed that chlorite and chlorate are able to induce chromosomal damage to plant systems, particularly chromosomal aberrations in A. cepa root tip cells, even at concentrations lower than the limit established by Italian normative law and WHO guidelines. In HepG2 cells increased DNA damage was only observed for chlorate at the lowest concentration. No increase in micronuclei frequency was detected in any of the samples tested in human HepG2 cells.     

Postharvest performance of fresh‐cut ‘Big Top’ nectarine as affected by dipping in chemical preservatives and packaging in modified atmosphere

Fresh‐cut ‘Big Top’ nectarines were dipped in 2% (w/v) ascorbic acid–1% (w/v) calcium lactate and stored at 4 °C for up to 12 days in 10 kPa O₂‐ and 10 kPa CO₂‐modified atmosphere packaging (MAP). The used microperforated plastic film allowed O₂ and CO₂ concentrations to reach steady values from the fifth day in storage onwards. Samples stored in MAP after chemical dipping showed the highest visual quality score, slight browning symptoms, increment in firmness and very low ethanol and acetaldehyde content. The chemical dipping also increased antioxidant capacity, probably due to the effect of ascorbic acid. The results suggested that the control of yeasts was mainly exerted by MAP, whereas only a slight effect was achieved by the chemical dipping. Therefore, MAP plus ascorbic acid/calcium lactate dipping was the best combination to preserve phytochemical content, antioxidant capacity and microbiological safety of fresh‐cut nectarines during storage.     

New PEEK-WC and PLA membranes for H2 separation

The potentialities of PEEK-WC (thermally treated at 120 °C) and PLA polymers have been studied in the field of membrane technology applied to H₂ separation/purification. In particular, for low/medium temperature operation (80 °C), PEEK-WC membranes (66 μm thick) showed good results in terms of H₂/CH₄ separation, showing an ideal selectivity value higher than 40. Meanwhile, we observed interesting selectivity also for H₂/N₂ and H₂/CO₂ separation, reaching values of 24 and 20, respectively. As expected, for PEEK-WC thermally treated membranes, the H₂ permeating flux increased from 25 to 80 °C and by increasing the transmembrane pressure. Furthermore, H₂ permeability at 80 °C was around 20 barrer. Concerning PLA membranes (26 μm thick), it is worth of noting that this polymer was pioneeristically used in this work as membrane application, showing great results in terms of H₂/CO₂ separation. Indeed, we overcame the Robeson's upper-bound (2008), achieving an ideal selectivity H₂/CO₂ around 25 with an H₂ permeability of 25 barrer. Further advantage due to the utilization of PLA membranes was related to the temperature operations set at ambient conditions, constituting a valuable and cost-effective solution for H₂/CO₂ separation processes via polymeric membrane technology.