Coupling Interrupted Fischer and Multicomponent Joullié-Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics

The generation of peptidomimetic substructures for medicinal chemistry purposes requires effective and divergent synthetic methods. We present in this work an efficient flow process that allows quick modulation of reagents for Joullié-Ugi multicomponent reaction, using spiroindolenines as core motifs. This sterically hindered imine equivalent could successfully be diversified using various isocyanides and amino acids in generally good space-time yields. A telescoped flow process combining interrupted Fischer reaction for spiroindolenine synthesis and subsequent Joullié-Ugi-type modification resulted in product formation in very good overall yield in less than 2 hours compared to 48 hours required in batch mode. The developed protocol can be seen as a general tool for rapid and facile generation of peptidomimetic compounds. We also showcase preliminary biological assessments for the prepared compounds.     

Experimental study on micro manufacturing of carbon nanotube (CNT) plastic composites

In recent years, innovative materials such as carbon nanotube composites are finding growing interest in several industrial sectors, from sports and leisure to electronics, automotive, aircraft, and defence. The reinforcing influence of the carbon nanotube is of prime interest. However, technological issues concerning the production methods and the manufacturing processes of carbon nanotube components limit the industrial application of this innovative and interesting material, especially whether small features are required. For this reason, manufacturing strategy involving new production technologies must be designed and developed. This paper studies the challenges of a manufacturing chain based on two manufacturing processes: injection moulding and micro milling. A case study based on these innovative processes is reported and discussed. The propagation chain effect and the influence of each considered process parameter on cutting force and geometrical accuracy of the features (the key characteristics of the process chain) were assessed by means of statistical analysis of variance (ANOVA). The ANOVA analysis demonstrated that cutting forces in micro milling are mainly influenced by the material and percentage of carbon nanotubes, while the main parameter influencing the geometrical accuracy of micro features is the matrix material.     

Validation of hot ring rolling industrial process 3D simulation

Ring rolling is a hot forming process used in the production of railway tyres, anti friction bearing races and different ring shaped work pieces for automotive energy production and aerospace applications. The advantages of ring rolling process include short production time, uniform quality, closed tolerances, good material quality and considerable saving in material cost. Despite the benefits some problems still exist according to a correct selection of the process parameters. Due to the nature of the process different rolling mills (driving, idle and axial rolls) are involved and the correct selection of the process parameters is not so feasible. Moreover an experimental approach to solve this problem risks to be more expensive. Actually FE codes are available to simulate the non linear problem that characterizes a ring rolling process. In this work a FE model, based on Deform 3D software, was tested versus experimental results acquired from an industrial plant. The accuracy of the FE model was analyzed through a dual comparison: by geometrical and by physical aspects. A good agreement was found between experimental and numerical results for both comparisons and, as a consequence, this code could be used in order to investigate and optimize the process parameters that characterize the ring rolling process in a virtual not expensive environment. The validated model will allow the studies of more environment-friend process configurations.     

Pragmatism or idealism? An urban perspective onto the politics of interurban cooperation for sustainability in the EU

European cities have been committed to achieve urban sustainability, participating in interurban networks dealing with socio-ecological issues. By examining the incentives derived by the involvement in these networks and the municipal political milieu where the decision about network participation is taken, this article seeks to understand the motivations for European cities to take part in sustainability networks. To do so, a small-N qualitative analysis was undertaken. The results show that cities’ participation in socio-ecological urban networks (SEUNs) is motivated by the economic, political and formative incentives that membership provides, and is influenced by institutionalised values, political agency and previous cooperative experience.     

Molecularly imprinted polymers by phase inversion technique for the selective recognition of saccharides of biomedical interest in aqueous solutions

The purpose of this work was the preparation and characterization of polymeric membranes for the selective recognition of saccharides using molecular imprinting technology associated with phase inversion. A system able to bind saccharides with high selectivity is particularly important in the pharmaceutical sector, since some of these compounds are constituents of molecules which can exert serious toxic effects even at very low concentrations. Two polymeric matrices were prepared using poly(ethylene‐co‐vinyl alcohol) copolymers, with an ethylene molar content of 32% and 44%, and were imprinted with two different saccharide molecules: maltose and 2‐keto‐3‐deoxy‐d ‐manno‐octulosonate (KDO). Matrices imprinted against maltose and KDO showed an easy template extraction, high binding capability and satisfactory selectivity, particularly for the matrix with an ethylene molar content of 44%. © 2017 Society of Chemical Industry     

Relevance of AIF/CypA Lethal Pathway in SH-SY5Y Cells Treated with Staurosporine

The AIF/CypA complex exerts a lethal activity in several rodent models of acute brain injury. Upon formation, it translocates into the nucleus of cells receiving apoptotic stimuli, inducing chromatin condensation, DNA fragmentation, and cell death by a caspase-independent mechanism. Inhibition of this complex in a model of glutamate-induced cell death in HT-22 neuronal cells by an AIF peptide (AIF(370-394)) mimicking the binding site on CypA, restores cell survival and prevents brain injury in neonatal mice undergoing hypoxia-ischemia without apparent toxicity. Here, we explore the effects of the peptide on SH-SY5Y neuroblastoma cells stimulated with staurosporine (STS), a cellular model widely used to study Parkinson’s disease (PD). This will pave the way to understanding the role of the complex and the potential therapeutic efficacy of inhibitors in PD. We find that AIF(370-394) confers resistance to STS-induced apoptosis in SH-SY5Y cells similar to that observed with CypA silencing and that the peptide works on the AIF/CypA translocation pathway and not on caspases activation. These findings suggest that the AIF/CypA complex is a promising target for developing novel therapeutic strategies against PD.     

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.     

Validation of a 1-Day Analytical Diagnostic Real-Time PCR for the Detection of Salmonella in Different Food Meat Categories

Foodborne disease caused by Salmonella represents a worldwide public health problem. In Europe, salmonellosis is still the second most commonly recorded zoonosis. Since the standard culture method for detecting Salmonella (ISO 6579:2002) requires up to 5 days to produce results, the need to develop rapid methods represents an important issue for the authorities and the producers. The aim of the present study was the in-house validation, according to ISO 16140, of an open-formula diagnostic real-time PCR for the detection of Salmonella in all the different meat categories reported in the EU Regulations relative to microbiological criteria for food safety. The assay employed specific primers and a probe target within the ttrRSBCA locus, which allows the tetrathionate respiration in Salmonella. Selectivity, relative accuracy, relative sensitivity and relative specificity were established by testing 110 bacterial strains and 175 various edible meat samples. Results showed 100 % selectivity, 100 % relative accuracy, 100 % relative sensitivity and 100 % relative specificity of the real-time PCR when compared to the standard culture method used as reference. In addition, in order to minimize the effect of the competitive micro-flora naturally present on meat samples, a highly nutritious and selective commercial medium (ONE Broth Salmonella, Oxoid) was evaluated in comparison with the classical non-selective pre-enrichment broth (buffered peptone water). Results demonstrated that the ONE Broth Salmonella medium increases the growth of Salmonella in the presence of competitive micro-flora.     

Effect of Formulation on Physicochemical Properties and Water Status of Nutritionally Enriched Fresh Pasta

A standard fresh pasta formulation (STD, the control sample) was modified by introducing soy and carrot ingredients both in dry and in liquid forms (soy and carrot flour and soy milk and carrot juice) to obtain eight nutritionally enriched fresh pasta samples with different formulations. The effect of formulation on selected physicochemical properties and water status of fresh pasta were studied. Colour, texture (force at rupture and extensibility), and cooking loss were found significantly affected by the formulation. Soy and carrot decreased the force at rupture and extensibility of fresh pasta and increased the solids loss during cooking. Improper gluten network development due to either a steric hindrance of soy and carrot solids or improper water availability for gluten hydration due to different water–solid interaction developed were hypothesized. Soy and carrot ingredients significantly altered the water dynamics in the pasta matrix at different space-time levels (macroscopic, moisture content and water activity; macromolecular, frozen water content; molecular, proton nuclear magnetic resonance relaxometry) of fresh pasta in a manner dependent upon the physical state of the added ingredient. Soy flour increased both the frozen water content and the overall proton mobility (¹H FID, ¹H T ₁ and T ₂) of fresh pasta while these parameters did not markedly differed from STD when soy milk was used. The presence of both carrot flour and carrot juice decreased significantly the frozen water content of fresh pasta but, at a molecular level, carrot flour altered the proton molecular mobility, while carrot juice did not.