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.     

Isotactic polypropylene solidification under pressure and high cooling rates. A master curve approach

Solidification in industrial processes very often involves flow fields, high thermal gradients and high pressures: the development of a model able to describe the polymer behavior becomes complex. Recently a new equipment has been developed and improved to study the crystallization of polymers when quenched under pressure. An experimental apparatus based on a modified, special injection moulding machine has been employed. Polymer samples can be cooled at a known cooling rate up to 100°C/s and under a constant pressure up to 40 MPa. Density, Micro Hardness (MH), Wide angle X‐ray diffraction (WAXD), and annealing measurements were then used to characterize the obtained sample morphology. Results on one iPP sample display a lower density and a lower density dependence on cooling rate for increasing pressure. Micro hardness confirms the same trend. A deconvolution technique of WAXD patterns is used to evaluate the final phase content of samples and to assess a crystallization kinetics behavior. A master curve approach to explain iPP behavior under pressure and high cooling rates was successfully applied on density results. On the basis of this simple model it is possible to predict the final polymer density by superposition of the effect of cooling rate and the effect of pressure in a wide range of experimental conditions.     

Flexible design‐planning of supply chain networks

Nowadays market competition is essentially associated to supply chain (SC) improvement. Therefore, the locus of value creation has shifted to the chain network. The strategic decision of determining the optimal SC network structure plays a vital role in the later optimization of SC operations. This work focuses on the design and retrofit of SCs. Traditional approaches available in literature addressing this problem usually utilize as departing point a rigid predefined network structure which may restrict the opportunities of adding business value. Instead, a novel flexible formulation approach which translates a recipe representation to the SC environment is proposed to solve the challenging design‐planning problem of SC networks. The resulting mixed integer linear programming model is aimed to achieve the best NPV as key performance metric. The potential of the presented approach is highlighted through illustrative examples of increasing complexity, where results of traditional rigid approaches and those offered by the flexible framework are compared. The implications of exploiting this potential flexibility to improve the SC performance are highlighted and are the subject of our further research work. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

Discovery of novel non-cyclam polynitrogenated CXCR4 coreceptor inhibitors

HIV cell fusion and entry have been validated as targets for therapeutic intervention against infection. Bicyclams were the first low-molecular-weight compounds to show specific interaction with CXCR4. The most potent bicyclam was AMD3100, in which the two cyclam moieties are tethered by a 1,4-phenylenebis(methylene) bridge. It was withdrawn from clinical trials owing to its lack of oral bioavailability and cardiotoxicity. We have designed a combinatorial library of non-cyclam polynitrogenated compounds by preserving the main features of AMD3100. At least two nitrogen atoms on each side of the p-phenylene moiety, one in the benzylic position and the other(s) in the heterocyclic system were maintained, and the distances between them were similar to the nitrogen atom distances in cyclam. A selection of diverse compounds from this library were prepared, and their in vitro activity was tested in cell cultures against HIV strains. This led to the identification of novel potent CXCR4 coreceptor inhibitors without cytotoxicity at the tested concentrations.     

Morphology and Properties of Polyethylene/Clay Nanocomposite Drawn Fibers

The influence of an elongational flow on the morphology of PE/clay nanocomposite drawn fibers was studied. An increase of the elastic modulus and the tensile strength as well as a decrease of the elongation at break are observed with increasing draw ratio. The applied elongational gradient orients the polymer chains and the clay particles along the spinning direction. When the applied flow results in the formation and the orientation of exfoliated nanoparticles, a pronounced increase of the mechanical properties is observed. The dispersed clay particles can be broken and oriented by the extensional flow, which might indicate a flow‐induced intercalated/exfoliated morphology transition.

     

Impedance spectroscopy on porous materials: A general model and application to graphite electrodes of lithium-ion batteries

Electrochemical impedance spectroscopy (EIS) was applied to porous negative graphite electrodes for lithium-ion batteries in the EC:DMC, 1 M LiPF₆ electrolyte. The effect of porosity on the electrode response time was studied and a theoretical model was developed, based on free path of the current lines between subsequent reaction sites. The effect of porosity on the electrode response is evidenced by the impedance spectra in which the high frequency capacitive semicircle is distorted. Fresh electrodes (before the formation of the solid electrolyte interphase, SEI) and cycled electrodes have different shapes of the impedance spectra indicating a change of processes at the surface. In particular, the shape of the spectrum for a fresh electrode can be related to an adsorption process. Impedance spectra of fresh electrodes were fitted using a simple model that considers porosity and the assumed electrochemical processes, giving good agreement between model and data. A correlation was found between adsorption sites and irreversible charge capacity in the first cycle.     

Direct evidence of oxygen evolution from Li1+ x (Ni1/3Mn1/3Co1/3)1? x O2 at high potentials

Li_1+x (Ni_1/3Mn_1/3Co_1/3)_1−x O₂ (NMC) oxides are among the most promising positive electrode materials for future lithium–ion batteries. A voltage “plateau” was observed on the first galvanostatic charging curve of NMC in the extended voltage region positive to 4.5 V vs. Li/Li⁺ for compounds with x > 0 (overlithiated compounds). Differences were observed in the cycling stability of the overlithiated and stoichiometric (x = 0) NMC oxides in this potential region. A differential plot of the charge vs. potential profile in the first cycle revealed that, for the overlithiated compounds, a large irreversible oxidative peak arises positive to 4.5 V vs. Li/Li⁺, while in the same potential region only a small peak due to the electrolyte oxidation is detected for the stoichiometric material. Differential Electrochemical Mass Spectrometry (DEMS) was used to investigate the high voltage region for both compounds and experimental evidence for oxygen evolution was provided for the overlithiated compounds at potentials positive to 4.5 V vs. Li/Li⁺. No oxygen evolution was detected for the stoichiometric compound.     

铝热反应制备纳米晶Fe_3Al过程中过冷度对晶粒尺寸的影响

利用C语言计算了铝热反应制备的纳米晶Fe3Al材料均质形核的相关热力学参数和纳米晶材料在不同条件下的平均晶粒尺寸,并通过试验对结果进行验证。结果表明,在形核率一定的情况下,Fe3Al的长大速率随过冷度的增大而增大;Fe3Al的平均晶粒尺寸在过冷度超过330K后均处于纳米级,其随过冷度的增大而逐渐减小,且当达到一定过冷度时,平均晶粒尺寸趋于一致,约37nm,该值与试验测定结果相符合。     

Contribution of Drugs Interfering with Protein and Cell Wall Synthesis to the Persistence of Pseudomonas aeruginosa Biofilms: An In Vitro Model

The occurrence of Pseudomonas aeruginosa (PA) persisters, including viable but non-culturable (VBNC) forms, subpopulations of tolerant cells that can survive high antibiotic doses, is the main reason for PA lung infections failed eradication and recurrence in Cystic Fibrosis (CF) patients, subjected to life-long, cyclic antibiotic treatments. In this paper, we investigated the role of subinhibitory concentrations of different anti-pseudomonas antibiotics in the maintenance of persistent (including VBNC) PA cells in in vitro biofilms. Persisters were firstly selected by exposure to high doses of antibiotics and their abundance over time evaluated, using a combination of cultural, qPCR and flow cytometry assays. Two engineered GFP-producing PA strains were used. The obtained results demonstrated a major involvement of tobramycin and bacterial cell wall-targeting antibiotics in the resilience to starvation of VBNC forms, while the presence of ciprofloxacin and ceftazidime/avibactam lead to their complete loss. Moreover, a positive correlation between tobramycin exposure, biofilm production and c-di-GMP levels was observed. The presented data could allow a deeper understanding of bacterial population dynamics during the treatment of recurrent PA infections and provide a reliable evaluation of the real efficacy of the antibiotic treatments against the bacterial population within the CF lung.