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1.
Adele Boccuto Filippo Dragoni Francesca Picarazzi Alessia Lai Carla Della Ventura Carla Veo Federica Giammarino Francesco Saladini Gianguglielmo Zehender Maurizio Zazzi Mattia Mori Ilaria Vicenti 《International journal of molecular sciences》2021,22(5)
The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC50) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC50 shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development. 相似文献
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Prof. Chiara Brullo Dr. Federica Rapetti Prof. Silvana Alfei Dr. Irena Maric Dr. Francesca Rizzelli Dr. Marina Mapelli Dr. Camillo Rosano Dr. Maurizio Viale Prof. Olga Bruno 《ChemMedChem》2020,15(11):961-969
Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here. 相似文献
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The Reciprocal Influences among Motivation,Personality Traits,and Game Habits for Playing Pokémon GO
Barbara Caci Fabrizio Scrima Marco Elio Tabacchi Maurizio Cardaci 《International journal of human-computer interaction》2019,35(14):1303-1311
This article reports a study exploring motivations of Pokémon Game use, individual differences related to personality traits, and game habits. First, it analyzed Pokémon GO motivations through exploratory factor analysis (EFA) by administering online the Pokémon GO Motivational Scale to a group of Italian gamers (N = 560). Successively, a Confirmatory Factor Analysis (CFA) was conducted testing three factorial models of Pokémon Game motivations on a selected random sample (N = 310). Results showed a three-factor model of Pokémon GO Game motivations (i.e. Personal Needs, Social Needs and Recreation), accounting for 68.9% of total variance plus a general higher order factor that best fits the data. Individual differences in Pokémon GO motivations and personality traits have been explored showing that high involved Pokémon GO players are introverted, low agreeableness, and conscientiousness people, driven by personal social and recreational needs. Reciprocal influences on motivational involvement, personality, and game habits were discussed. 相似文献
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Massimo Dal Monte Maurizio Cammalleri Rosario Amato Salvatore Pezzino Roberta Corsaro Paola Bagnoli Dario Rusciano 《International journal of molecular sciences》2020,21(23)
Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health. 相似文献
6.
María T. Colomer Lidia Zur Maurizio Ferrari Angel L. Ortiz 《Ceramics International》2018,44(11):11993-12001
Rhabdophane-type Eu3+,Tb3+-codoped LaPO4·nH2O single-crystal nanorods with the compositions La0.99999-xEuxTb0.00001PO4·nH2O (x?=?0–0.03), La0.99999-yTbyEu0.00001PO4·n′H2O (y?=?0–0.010), and La0.99999-zTbzEu0.000007PO4·n′′H2O (z?=?0–0.012) were hydrothermally synthesized with microwaves. It is shown that the Eu3+,Tb3+ codoping does not affect the thermal stability of these nanorods, which is due to the formation of substitutional solid solutions with both Eu3+ and Tb3+ replacing La3+ in the crystal lattice. Moreover, it is also shown that monazite-type Eu3+,Tb3+-codoped LaPO4 single-crystal nanorods can be obtained by calcining their rhabdophane-type Eu3+,Tb3+-codoped LaPO4·(n,n′ or n′′)H2O counterparts at moderate temperature in air, and that they are thermally stable. It is also observed that, for the same Eu3+,Tb3+-codoping content, the monazite-type Eu3+,Tb3+-codoped LaPO4 nanorods exhibit higher photoluminescent efficiency than the rhabdophane-type Eu3+,Tb3+-codoped LaPO4· (n,n′ or n′′)H2O nanorods. Moreover, it is found that the highest photoluminescence emission corresponds to the monazite-type La0.96999Eu0.02Tb0.00001PO4 nanorods for the La0.99999-xEuxTb0.00001PO4 system. However, for those compositions energy transfer from Tb3+ to Eu3+ does not occur. In addition, for an efficient energy transfer to occur, a content of at least 1?mol% Tb3+ is needed in all the studied materials. 相似文献
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Desiccant cooling systems (DCS) represent a suitable alternative to conventional systems for air-conditioning purposes. Their benefits should be correctly assessed by means of dynamic simulations, taking into account both the operating context and the available control variables. Several models are available in literature to model solid DCS based on desiccant wheels (DW). Nevertheless, physical models are rather complex to be implemented in dynamic simulation tools of building-integrated energy systems, while constant effectiveness models have low performance. Regression models can represent a suitable alternative, as they can provide high accuracy but with a low modeling effort. In this paper, experimental data are used to develop correlations to predict the dehumidification and thermal performance of a DW, as a function of inlet air temperature and humidity ratio, regeneration temperature, air flow rates, and rotational speed. Statistical tools are used to investigate the effect of those independent operating variables. Furthermore, the selection software provided by another DW manufacturer is used to generate operational data of a further desiccant rotor and to derive the related correlations. At last, the proposed model is compared with the correlations found in the relevant literature. The results show that a very good agreement is found in the comparison between measured and predicted values, with maximum relative errors not higher than 5%. Furthermore, an excellent behavior of the proposed model is also found when it is used to simulate a generic desiccant wheel, without the need of a detailed physical model. Finally, a better agreement is found with respect to other models based on correlations developed in literature, even using a higher number of coefficients to be calibrated. 相似文献
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