NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease

Standard treatment for advanced non-small cell lung cancer (NSCLC) historically consisted of systemic cytotoxic chemotherapy until the early 2000s, when precision medicine led to a revolutionary change in the therapeutic scenario. The identification of oncogenic driver mutations in EGFR, ALK and ROS1 rearrangements identified a subset of patients who largely benefit from targeted agents. However, since the proportion of patients with druggable alterations represents a minority, the discovery of new potential driver mutations is still an urgent clinical need. We provide a comprehensive review of the emerging molecular targets in NSCLC and their applications in the advanced setting.     

Tissue Engineering and Regenerative Medicine in Pediatric Urology: Urethral and Urinary Bladder Reconstruction

In the case of pediatric urology there are several congenital conditions, such as hypospadias and neurogenic bladder, which affect, respectively, the urethra and the urinary bladder. In fact, the gold standard consists of a urethroplasty procedure in the case of urethral malformations and enterocystoplasty in the case of urinary bladder disorders. However, both surgical procedures are associated with severe complications, such as fistulas, urethral strictures, and dehiscence of the repair or recurrence of chordee in the case of urethroplasty, and metabolic disturbances, stone formation, urine leakage, and chronic infections in the case of enterocystoplasty. With the aim of overcoming the issue related to the lack of sufficient and appropriate autologous tissue, increasing attention has been focused on tissue engineering. In this review, both the urethral and the urinary bladder reconstruction strategies were summarized, focusing on pediatric applications and evaluating all the biomaterials tested in both animal models and patients. Particular attention was paid to the capability for tissue regeneration in dependence on the eventual presence of seeded cell and growth factor combinations in several types of scaffolds. Moreover, the main critical features needed for urinary tissue engineering have been highlighted and specifically focused on for pediatric application.     

Modeling Self-Rollable Elastomeric Films for Building Bioinspired Hierarchical 3D Structures

In this work, an innovative model is proposed as a design tool to predict both the inner and outer radii in rolled structures based on polydimethylsiloxane bilayers. The model represents an improvement of Timoshenko’s formula taking into account the friction arising from contacts between layers arising from rolling by more than one turn, hence broadening its application field towards materials based on elastomeric bilayers capable of large deformations. The fabricated structures were also provided with surface topographical features that would make them potentially usable in different application scenarios, including cell/tissue engineering ones. The bilayer design parameters were varied, such as the initial strain (from 20 to 60%) and the bilayer thickness (from 373 to 93 µm). The model matched experimental data on the inner and outer radii nicely, especially when a high friction condition was implemented in the model, particularly reducing the error below 2% for the outer diameter while varying the strain. The model outperformed the current literature, where self-penetration is not excluded, and a single value of the radius of spontaneous rolling is used to describe multiple rolls. A complex 3D bioinspired hierarchical elastomeric microstructure made of seven spirals arranged like a hexagon inscribed in a circumference, similar to typical biological architectures (e.g., myofibrils within a sarcolemma), was also developed. In this case also, the model effectively predicted the spirals’ features (error smaller than 18%), opening interesting application scenarios in the modeling and fabrication of bioinspired materials.     

The effects of hot isostatic pressing (HIP) and solubilization heat treatment on the density,mechanical properties,and microstructure of austenitic stainless steel parts produced by selective laser melting (SLM)

Despite ongoing optimization, selective laser melting (SLM) technology still cannot guarantee the production of completely defect-free components. This wor     

Silver electrodeposition from air and water-stable ionic liquid: An environmentally friendly alternative to cyanide baths

The influence of temperature on the kinetics and the morphology of silver deposits obtained from an air and water-stable ionic liquid (the 1-butyl-3-methyl imidazolium tetrafluoroborate) was studied by means of cyclic voltammetry and chronoamperometry. The nucleation and growth mechanisms have been investigated and the effect of temperature evaluated up to 200 °C. Dense, pure and very thin (about 0.3 μm) silver coatings, with decorative properties, have been obtained on commercial copper electrodes at different temperatures. The characterization of the deposits morphology has been performed by visual investigation and SEM microscopy. Data about thickness were acquired by Calotest® measurements. The deposits result constituted by pure silver as determined by combination of EDX microanalysis and Auger Electron Spectroscopy (AES). The deposition method promises to be a new, environmentally friendly, method for silver electrodeposition which is the reason for the absence of cyanide and volatile toxic solvents in the electroplating bath.     

Physical,dynamic-mechanical and thermogravimetric analysis of aromatic and cycloaliphatic-based poly(urethaneurea)s

Experimental batches of linear rubber-like polyurethanes characterized by the presence of chemically different hard segments are studied and their thermal and dynamic-mechanical properties are related to the differences in chemical compositions. Interesting correlations are found between the development of crystallinity in such elastomeric poly(urethaneurea)s and the aromatic or alicyclic nature of the diisocyanate. Moreover, for a fixed ratio between hard and soft segments, and for a given composition of the soft segment, the results seem to indicate a better degree of phase separation in cycloaliphatic-based hard segment poly(urethaneurea)s than in aromatic-based hard segment poly(urethaneurea)s.     

SKPFM investigations of intermetallic compounds of innovative Er‐ and Zr‐containing Al–Si–Mg alloys and their influence on corrosion localization in saline solution

The paper aims at characterizing the influence of intermetallic compounds on the corrosion localization of innovative Al–Si–Mg Er‐ and Zr‐containing casting alloys. Samples of the investigated materials were studied by means of optical and scanning electron microscope micrographs, immersion tests, and scanning Kelvin probe force microscope (SKPFM) analyses in the T6 temper. Combination of immersion tests and SKPFM analyses allowed to identify those classes of intermetallic compounds promoting localization of the corrosion process. It was found that intermetallic compounds richer in Fe were the most critical for corrosion localization; furthermore, additions of Er caused a marked decrease of the potential difference of intermetallic compounds with respect to the Al matrix and a consequent less intense microgalvanic coupling, which translates into slower corrosion kinetics. Further, Zr additions slightly increased the potential difference of intermetallic compounds with the Al matrix, promoting a faster corrosion process.     

Inhibition of soybean lipoxygenase-1 by chain-breaking antioxidants

The aim of this investigation was to determine whether chain-breaking antioxidants able to prevent lipid peroxidation can inhibit lipoxygenase-1 (EC 1.13.11.12). Therefore, the effects of ascorbic acid, 6-palmitoylascorbic acid and trolox on the enzyme activity were analyzed by means of Lineweaver-Burk double reciprocal plots and Yoshino's graphical method. The effect of these compounds on the formation of free radicals during lipoxygenase-1 reaction was investigated as well, by monitoring the enzymic formation of oxodienes. We present evidence that the chain-breaking antioxidants ascorbic acid, 6-palmitoylascorbic acid and trolox inhibit soybean lipoxygenase-1 in the micromolar concentration range (Ki 27, 3 and 18 μM, respectively). The inhibition is competitive, complete and reversible. All three compounds trap the free radicals formed during the lipoxygenase-catalyzed reaction, which might substantially contribute to their inhibitory ability. These findings can have physiological significance in the light of the lipoxygenase involvement in biomembrane remodelling.     

2015年世博会卡里塔斯展馆及埃内尔展馆 意大利米兰

正Piuarch建筑师事务所负责设计了2015年米兰世博会埃内尔(意大利国家电力公司)展馆及卡里塔斯展馆。为了将客户想表达的含义与价值观更好地传达给观众,Piuarch选择了一种特殊的建筑语言来体现两个展馆的特点。埃内尔展馆沿东西大街而建,占地900平方米。设计体现出智能电网这一概念,传达出以智能科技优化世博会整体用电的理念。