Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.     

Synthesis,Pharmacological Evaluation,and Docking Studies of Novel Pyridazinone‐Based Cannabinoid Receptor Type 2 Ligands

In recent years, cannabinoid type 2 receptors (CB₂R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB₂R are devoid of the psychoactive effects typically observed for CB₁R ligands. Based on our recent studies on a class of pyridazinone 4‐carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure–activity relationships for this promising scaffold with the aim to develop potent CB₂R ligands. In binding assays, two of the new synthesized compounds [6‐(3,4‐dichlorophenyl)‐2‐(4‐fluorobenzyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2,3‐dihydropyridazine‐4‐carboxamide ( 2 ) and 6‐(4‐chloro‐3‐methylphenyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2‐pentyl‐2,3‐dihydropyridazine‐4‐carboxamide ( 22 )] showed high CB₂R affinity, with K_i values of 2.1 and 1.6 nm , respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB₂R inverse agonists. Compound 22 displayed the highest CB₂R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle‐switch residue, W6.48.     

Survey of 1,2-dicarbonyl compounds in commercial honey of different floral origin

In this study we conducted a survey of the concentrations of the major 1,2-dicarbonyl compounds in 40 commercial honey samples from 12 different floral origins. 3-Deoxyglucosone (3-DG), glyoxal (GO), and methylglyoxal (MGO) were measured, using their corresponding quinoxaline derivatives, by high-performance liquid chromatography (HPLC). The analytical performance of the HPLC method for the analysis of 1,2-dicarbonyl compounds was evaluated in terms of linearity, limits of detection (LODs), limits of quantification (LOQs), and precision. Linearity over 2 orders of magnitude, LODs (0.01-0.04 mg/kg), and LOQs (0.03-0.12 mg/kg) were calculated. Instrumental precision, as measured by the repeatability relative standard deviation% (RSDr%), was found to be between 0.22% and 0.55%. Furthermore, the concentrations of factors GO and MGO with respect to 3-DG were also calculated for rapid quantification in honey. In honey samples, the concentrations of 3-DG ranged from 75.9 to 808.6 mg/kg and were significantly higher (up to 100-fold) than those of 5-hydroxymethylfurfural (HMF). Values for GO and MGO were 0.1-10.9 and 0.2-2.9 mg/kg, respectively. The chemical characteristics that most influenced the levels of 1,2-dicarbonyl compounds in honey were found to be pH and total phenols. This was supported by multivariate analysis used to classify different honey types with respect to their chemical characteristics. In addition, both dicarbonyls and phenols are believed to contribute to the development of the final color of honey.     

High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy

Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; p = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer.     

Theoretical study and performance evaluation of hydrogen production by 200 W solid oxide electrolyzer stack

High temperature steam electrolyzers, taking advantage of high temperature heat, can produce more hydrogen by using less electrical energy than low temperature electrolyzers. This paper presents an experimental study on hydrogen production by using a 200 W solid oxide stack working in reverse mode. A thermodynamic study of the process was performed by measuring the heat and mass balance of stack at different operating conditions. Different definitions of efficiency were used to highlight the limit and potential of the process. The I–V curve, the flow rate measurements and the GC analysis on outlet flows were used to calculate the hydrogen and oxygen productions. In addition, the influence of steam dilution, water utilization and operating temperature on conversion efficiency and stack's thermal balance was evaluated. With this aim, the tests were performed at three operating temperature (700 °C, 750 °C and 800 °C) over a range of steam inlet concentration from 50% to 90% and water utilization up to 70%. The hydrogen and oxygen flows produced by electrolysis, at different loads, were directly measured after water condensation: net flows up to 2.4 ml/(min cm²) of hydrogen and 1.2 ml/(min cm²) of oxygen were measured and compared to the theoretical ones, showing a good agreement.     

The territorial and landscape impacts of photovoltaic systems: Definition of impacts and assessment of the glare risk

The installation and operation of systems that exploit solar energy through photovoltaic conversion, recently promoted in some European countries by new sell-back tariffs, is a relevant transformation of the territory for various reasons (land use, elimination of the existing vegetation, visual impact on the components of the landscape, microclimate change, glare from the reflection of the direct sunlight). The weak energy intensity of the solar source coupled with the low conversion efficiency of the photovoltaic cells, make the physical dimensions of such systems relevant and, with them, also the environmental, territorial and landscape impacts that basically depend on the physical extent of the system. If it is well known that an incentive to the exploitation of renewable sources is one of the features of the policy of land conservation, including the one of the protected areas, at the same time the concerns of local communities and governments about the environmental, territorial and landscape impacts of this technology are increasing rapidly.Given this picture, this work is intended to clarify the territorial impacts of the ground mounted photovoltaic systems. Later, the paper concentrates on a specific impact, which is the assessment of the risk of glare by reflection of direct sunlight from the surfaces of photovoltaic modules. The methodologies that can be used to assess this impact and the outcomes of an evaluation carried out for a 5000 m² PV system currently designed on a hilly territory in Italy are presented.     

Influence of liquid lead and lead-bismuth eutectic on tensile, fatigue and creep properties of ferritic/martensitic and austenitic steels for transmutation systems

In this paper, the tensile, fatigue and creep properties of the Ferritic/Martensitic (F/M) steel T91 and of the Austenitic Stainless (AS) Steel 316L in lead-bismuth eutectic (LBE) or lead, obtained in the different organizations participating to the EUROTRANS-DEMETRA project are reviewed. The results show a remarkable consistency, referring to the variety of metallurgical and surface state conditions studied. Liquid Metal Embrittlement (LME) effects are shown, remarkable on heat-treated hardened T91 and also on corroded T91 after long-term exposure to low oxygen containing Liquid Metal (LM), but hardly visible on passive or oxidized smooth T91 specimens. For T91, the ductility trough was estimated, starting just above the melting point of the embrittler (T_M,E = 123.5 °C for LBE, 327 °C for lead) with the ductility recovery found at 425 °C. LME effects are weaker on 316L AS steel. Liquid Metal Assisted Creep (LMAC) effects are reported for the T91/LBE system at 550 °C, and for the T91/lead system at 525 °C. Today, if the study of the LME effects on T91 and 316L in LBE or lead can be considered well documented, in contrast, complementary investigations are necessary in order to quantify the LMAC effects in these systems, and determine rigorously the threshold creep conditions.     

Coping strategies and collective efficacy as mediators between stress appraisal and quality of life among rescue workers.

Fire-fighters, paramedics, and emergency medical technicians routinely confront potentially traumatic events in the course of their jobs. The mediation role of coping strategies and collective efficacy in the relationship between stress appraisal and quality of life was examined (compassion satisfaction, compassion fatigue, and burnout) in a correlational study. Participants were 463 Italian rescue workers (fire fighters and different categories of emergency health care professionals). Participants filled out measures of stress appraisal, collective efficacy, coping strategies, and quality of life. The results showed that emotion and support coping, self-blame coping, and self-distraction mediated the relationship between stress appraisal and compassion fatigue. Moreover, collective efficacy, self-blame coping, and religious coping mediated the relationship between stress appraisal and burnout. Finally, collective efficacy, self-blame coping, and problem-focused coping mediated the relationship between stress appraisal and compassion satisfaction. Cognitive restructuring and denial did not mediate the relation between stress appraisal and any of the quality of life dimensions. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Evaluation of the laboratory prediction of surface properties of bituminous mixtures

An experimental and analytical investigation was carried out both in laboratory and in situ on wearing courses. The approach presented in this paper aims to predict the in situ density and surface properties of bituminous layers, during the phase of mix design in laboratory. Therefore, the main attempt of this study is to identify, amongst the commonly available laboratory equipments, the most adequate for producing specimens that, used for carrying out simple and reliable laboratory test, allow the prediction of the surface characteristics of the mixture as laid on site.This is done by comparing the data collected from an experimental site with those calculated from laboratory specimens compacted with the superpave gyratory compactor (SGC).Typical laboratory tests (such as the sand patch method and the skid test) as well as the surface data obtained with a laser profilometer have been considered for characterizing the properties of a standard Italian wearing course, laid in two different final thicknesses and produced with the most common raw materials, according to the currently used techniques for mixtures production and laying process for maintenance work. An evaluation of the SGC ability to represent the density and surface properties of the mixture once on site is then discussed.