Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological,Immunohistochemical and Gene Expression Profiles

Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.     

Effect of lithium intercalation on the photovoltaic performances of photovoltachromic cells

In the last few years, a new class of smart multifunctional photoelectrochemical devices has been attracting the interest of several academic institutions and industrial companies: photovoltachromic cells, combining the features of photoelectrochromic cells with those of dye‐sensitized solar cells. Here, we report the results of a detailed electrochemical analysis aiming at investigating the electrochemical behavior of these complex photoelectrochemical devices. In particular, we have been focused on the effect of Li⁺ ions displacement during the coloration of the electrochromic tungsten oxide on the performances of the photovoltaic unit. As we had previously observed striking differences between the performances of the barely photovoltaic mode (with the tungsten oxide in the bleached state) and the photovoltachromic mode (with the tungsten oxide in the colored state), we thus attempted to provide a reasonable physical interpretation to the observed phenomena. Copyright © 2013 John Wiley & Sons, Ltd.     

Self-nucleation of isotactic poly(1-butene) in the trigonal modification

Isotactic poly(1-butene) (i-PBu) is a polyolefin of industrial relevance which exhibits an interesting polymorphism. Upon cooling from the relaxed melt at atmospheric pressure, a tetragonal phase (Form II) develops. However, being metastable, this structure slowly evolves upon aging in the stable trigonal modification (Form I). Another trigonal modification, denoted Form I′, can also crystallize directly from the melt if proper conditions are met, e.g., high pressure, low tacticity, ultrathin samples etc. In this work, we aim to verify whether, by acting on the nucleation stage via a proper thermal history, the direct formation of the trigonal polymorph from the melt in a bulk sample is possible. Nucleation of i-PBu has been tailored by means of the self-nucleation technique, imposed on previously aged samples (Form I). DSC and temperature-resolved WAXS show that different crystallization pathways can be observed, depending on the residual concentration of Form I self-nuclei. With decreasing self-nucleation temperature we first encounter “cross-nucleation” of the tetragonal crystal on trigonal nuclei, followed by concomitant crystallization of Form II and Form I′ and eventually the sole formation of the trigonal modification (Form I′).     

A global approach to the design of discrete-time cellular neural networks for associative memories

In this paper a global design method for associative memories using discrete-time cellular neural networks (DTCNNs) is presented. The proposed synthesis technique enables to realize associative memories with several advantageous features. First of all, grey-level as well as bipolar images can be stored. Moreover, the proposed approach generates networks with learning and forgetting capabilities. Finally, it is possible to design networks with any kind of predetermined interconnection structure. In particular, neighbourhoods without line crossings can be chosen, greatly simplifying the VLSI implementation of the designed DTCNNs. In the first part of this work a model of a multilevel threshold network is presented and a stability analysis is carried out using basic notions deriving from non-linear dynamical system theory. The synthesis procedure is then developed by means of a pseudoinversion technique, assuring learning and forgetting capabilities of the designed DTCNN. The use of a neighbourhood without line crossings is also discussed. Simulation results are reported to show the capability of the proposed approach.     

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.     

Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification.     

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.