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31.
Enrico Mario Alessandro Fassi Mariangela Garofalo Jacopo Sgrignani Michele Dei Cas Matteo Mori Gabriella Roda Andrea Cavalli Giovanni Grazioso 《International journal of molecular sciences》2022,23(9)
(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and Kd values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules. 相似文献
32.
Fernando Fraternali Matteo Negri Michael Ortiz 《International Journal of Fracture》2010,166(1-2):3-11
Free discontinuity problems arising in the variational theory for fracture mechanics are considered. A Γ -convergence proof for an r-adaptive 3D finite element discretization is given in the case of a brittle material. The optimal displacement field, crack pattern and mesh geometry are obtained through a variational procedure that encompasses both mechanical and configurational forces. Possible extensions to cohesive fracture and quasi-static evolutions are discussed. 相似文献
33.
Massimo Lorusso Alberta Aversa Diego Manfredi Flaviana Calignano Elisa Paola Ambrosio Daniele Ugues Matteo Pavese 《Journal of Materials Engineering and Performance》2016,25(8):3152-3160
Direct metal laser sintering (DMLS) is an additive manufacturing technique for the production of parts with complex geometry and it is especially appropriate for structural applications in aircraft and automotive industries. Aluminum-based metal matrix composites (MMCs) are promising materials for these applications because they are lightweight, ductile, and have a good strength-to-weight ratio This paper presents an investigation of microstructure, hardness, and tribological properties of AlSi10Mg alloy and AlSi10Mg alloy/TiB2 composites prepared by DMLS. MMCs were realized with two different compositions: 10% wt. of microsize TiB2, 1% wt. of nanosize TiB2. Wear tests were performed using a pin-on-disk apparatus on the prepared samples. Performances of AlSi10Mg samples manufactured by DMLS were also compared with the results obtained on AlSi10Mg alloy samples made by casting. It was found that the composites displayed a lower coefficient of friction (COF), but in the case of microsize TiB2 reinforcement the wear rate was higher than with nanosize reinforcements and aluminum alloy without reinforcement. AlSi10Mg obtained by DMLS showed a higher COF than AlSi10Mg obtained by casting, but the wear rate was higher in the latter case. 相似文献
34.
Raffaele Raimondi Piero Zollet Francesco Paolo De Rosa Panagiotis Tsoutsanis Matteo Stravalaci Marianna Paulis Antonio Inforzato Mario R. Romano 《International journal of molecular sciences》2022,23(2)
The retinal pigmented epithelium (RPE) plays a pivotal role in retinal homeostasis. It is therefore an interesting target to fill the unmet medical need of different retinal diseases, including age-related macular degeneration and Stargardt disease. RPE replacement therapy may use different cellular sources: induced pluripotent stem cells or embryonic stem cells. Cells can be transferred as suspension on a patch with different surgical approaches. Results are promising although based on very limited samples. In this review, we summarize the current progress of RPE replacement and provide a comparative assessment of different published approaches which may become standard of care in the future. 相似文献
35.
Davide Loizzo Savio Domenico Pandolfo Devin Rogers Clara Cerrato Nicola Antonio di Meo Riccardo Autorino Vincenzo Mirone Matteo Ferro Camillo Porta Alessandro Stella Cinzia Bizzoca Leonardo Vincenti Marco Spilotros Monica Rutigliano Michele Battaglia Pasquale Ditonno Giuseppe Lucarelli 《International journal of molecular sciences》2022,23(7)
Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible. 相似文献
36.
Chiara Paolini Silvia Agarbati Devis Benfaremo Matteo Mozzicafreddo Silvia Svegliati Gianluca Moroncini 《International journal of molecular sciences》2022,23(7)
Systemic sclerosis (SSc) is a clinically heterogeneous disorder of the connective tissue characterized by vascular alterations, immune/inflammatory manifestations, and organ fibrosis. SSc pathogenesis is complex and still poorly understood. Therefore, effective therapies are lacking and remain nonspecific and limited to disease symptoms. In the last few years, many molecular and cellular mediators of SSc fibrosis have been described, providing new potential options for targeted therapies. In this review: (i) we focused on the PDGF/PDGFR pathway as key signaling molecules in the development of tissue fibrosis; (ii) we highlighted the possible role of stimulatory anti-PDGFRα autoantibodies in the pathogenesis of SSc; (iii) we reported the most promising PDGF/PDGFR targeting therapies. 相似文献
37.
38.
A simple top-down fabrication technique that involves scanning probe lithography on Si is presented. The writing procedure consists of a chemically selective patterning in mesitylene. Operating in an organic media is possible to perform local oxidation or solvent decomposition during the same pass by tuning the applied bias. The layer deposited with a positively biased tip with sub-100-nm lateral resolution consists of nanocrystalline graphite, as verified by Raman spectroscopy. The oxide pattern obtained in opposite polarization is later used as a mask for dry etching, showing a remarkable selectivity in SF6 plasma, to produce Si nanofeatured molds. 相似文献
39.
Gilbert D. Nessim Matteo Seita Desirée L. Plata Kevin P. O’Brien A. John Hart Eric R. Meshot Christopher M. Reddy Philip M. Gschwend Carl V. Thompson 《Carbon》2011,49(3):804-810
Despite significant progress in carbon nanotube (CNT) synthesis by thermal chemical vapor deposition (CVD), the factors determining the structure of the resulting carbon filaments and other graphitic nanocarbons are not well understood. Here, we demonstrate that gas chemistry influences the crystal structure of carbon filaments grown at low temperatures (500 °C). Using thermal CVD, we decoupled the thermal treatment of the gaseous precursors (C2H4/H2/Ar) and the substrate-supported catalyst. Varying the preheating temperature of the feedstock gas, we observed a striking transition between amorphous carbon nanofibers (CNFs) and crystalline CNTs. These results were confirmed using both a hot-wall CVD system and a cold-wall CVD reactor. Analysis of the exhaust gases (by ex situ gas chromatography) showed increasing concentrations of specific volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs) that correlated with the structural transition observed (characterized using high-resolution transmission electron microscopy). This suggests that the crystallinity of carbon filaments may be controlled by the presence of specific gas phase precursor molecules (e.g., VOCs and PAHs). Thus, direct delivery of these molecules in the CVD process may enable selective CNF or CNT formation at low substrate temperatures. The inherent scalability of this approach could impact many promising applications, especially in the electronics industry. 相似文献
40.
Prevention of steel corrosion in concrete exposed to seawater with submerged sacrificial anodes 总被引:2,自引:0,他引:2
Luca Bertolini Matteo GastaldiMariaPia Pedeferri Elena Redaelli 《Corrosion Science》2002,44(7):1497-1513
This paper presents the results of a study of the effectiveness of submerged sacrificial anodes in preventing the onset of pitting corrosion in the emerged part of marine piles. Experimental tests were carried out on reinforced concrete columns with steel embedded both in chloride free concrete and chloride contaminated concrete in order to compare the effects of sacrificial anodes on passive steel and on corroding steel. Results have shown, at least under the present testing conditions, that sacrificial anodes may be more effective in preventing corrosion initiation (i.e. in providing cathodic prevention) than in controlling ongoing pitting corrosion (i.e. in guaranteeing cathodic protection). Monitoring criteria for this type of prevention are also discussed. 相似文献