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排序方式: 共有4179条查询结果,搜索用时 15 毫秒
81.
Laura Mannarino Lara Paracchini Federica Pezzuto Gheorghe Emilian Olteanu Laura Moracci Luca Vedovelli Irene De Simone Cristina Bosetti Monica Lupi Rosy Amodeo Alessia Inglesi Maurizio Callari Serena Penpa Roberta Libener Sara Delfanti Antonina De Angelis Alberto Muzio Paolo Andrea Zucali Paola Allavena Giovanni Luca Ceresoli Sergio Marchini Fiorella Calabrese Maurizio DIncalci Federica Grosso 《International journal of molecular sciences》2022,23(10)
82.
Alberto Pla-Lpez Raquel Castillo Rocío Cejudo-Marín Olaya García-Pedrero Mariam Bakir-Laso Eva Falomir Miguel Carda 《International journal of molecular sciences》2022,23(13)
Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound 23, bearing a p-chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel®. 相似文献
83.
Adelina Orellana Pablo García-Gonzlez Sergi Valero Laura Montrreal Itziar de Rojas Isabel Hernndez Maitee Rosende-Roca Liliana Vargas Juan Pablo Tartari Ester Esteban-De Antonio Urszula Bojaryn Leire Narvaiza Emilio Alarcn-Martín Montserrat Alegret Daniel Alcolea Alberto Lle Lluís Trraga Vanesa Pytel Amanda Cano Marta Marqui Merc Boada Agustín Ruiz 《International journal of molecular sciences》2022,23(13)
Background: Clinical diagnosis of Alzheimer’s disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases. Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST® ELISA and Lumipulse G® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer’s disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647). Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing–Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland–Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan–Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates (p = 9.815−27). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression. Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects. 相似文献
84.
Rocío Fernndez-Serra Emma Martínez-Alonso Alberto Alczar Mourad Chioua Jos Marco-Contelles Ricardo Martínez-Murillo Milagros Ramos Gustavo V. Guinea Daniel Gonzlez-Nieto 《International journal of molecular sciences》2022,23(13)
Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies. 相似文献
85.
86.
Emanuele Bertarelli Alberto Corigliano Andreas Greiner Jan G. Korvink 《Microsystem Technologies》2011,17(1):165-173
A novel design strategy to avoid pull-in occurrence in electrostatic micro electro mechanical systems is proposed. It combines
charge control with ring electrodes, on a circular geometry. This idea is introduced here for the design of efficient and
reliable high stroke electrostatic diaphragm micropumps, while it has a broad potential applicability. A minimal lumped one
degree-of-freedom model is derived and used to introduce and demonstrate the proposed approach for a circular plate geometry.
Finite element models are subsequently adopted for a more detailed device modelling. As expected, charge control exhibits
a stabilizing effect with respect to voltage drive, but not sufficient to achieve a full-range stability for the considered
geometry. When the electrode area is properly defined, stability range can be extended up to gap closure in the central part
of the membrane. In this configuration, the increase in voltage required for full-range device drive would be relevant, while
in charge control the penalty is considerably lower. Finally, loading conditions and geometrical parameters for an optimized
actuation are suggested. 相似文献
87.
Inclusion dynamics hybrid automata 总被引:2,自引:0,他引:2
Alberto Casagrande Carla Piazza Alberto Policriti Bud Mishra 《Information and Computation》2008,206(12):1394-1424
Hybrid systems are dynamical systems with the ability to describe mixed discrete-continuous evolution of a wide range of systems. Consequently, at first glance, hybrid systems appear powerful but recalcitrant, neither yielding to analysis and reasoning through a purely continuous-time modeling as with systems of differential equations, nor open to inferential processes commonly used for discrete state-transition systems such as finite state automata. A convenient and popular model, called hybrid automata, was introduced to model them and has spurred much interest on its tractability as a tool for inference and model checking in a general setting. Intuitively, a hybrid automaton is simply a “finite-state” automaton with each state augmented by continuous variables, which evolve according to a set of well-defined continuous laws, each specified separately for each state. This article investigates both the notion of hybrid automaton and the model checking problem over such a structure. In particular, it relates first-order theories and analysis results on multivalued maps and reduces the bounded reachability problem for hybrid automata whose continuous laws are expressed by inclusions (x′f(x,t)) to a decidability problem for first-order formulæ over the reals. Furthermore, the paper introduces a class of hybrid automata for which the reachability problem can be decided and shows that the problem of deciding whether a hybrid automaton belongs to this class can be again decided using first-order formulæ over the reals. Despite the fact that the bisimulation quotient for this class of hybrid automata can be infinite, we show that our techniques permit effective model checking for a nontrivial fragment of CTL. 相似文献
88.
89.
Cesare Faldini Marco Manzetti Simona Neri Francesca Barile Giovanni Viroli Giuseppe Geraci Francesco Ursini Alberto Ruffilli 《International journal of molecular sciences》2022,23(11)
Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field. 相似文献
90.
Elisa Di Fabio Antonia Iazzetti Alessio Incocciati Valentina Caseli Giancarlo Fabrizi Alberto Boffi Alessandra Bonamore Alberto Macone 《International journal of molecular sciences》2022,23(12)
Amine oxidases are enzymes belonging to the class of oxidoreductases that are widespread, from bacteria to humans. The amine oxidase from Lathyrus cicera has recently appeared in the landscape of biocatalysis, showing good potential in the green synthesis of aldehydes. This enzyme catalyzes the oxidative deamination of a wide range of primary amines into the corresponding aldehydes but its use as a biocatalyst is challenging due to the possible inactivation that might occur at high product concentrations. Here, we show that the enzyme’s performance can be greatly improved by immobilization on solid supports. The best results are achieved using amino-functionalized magnetic microparticles: the immobilized enzyme retains its activity, greatly improves its thermostability (4 h at 75 °C), and can be recycled up to 8 times with a set of aromatic ethylamines. After the last reaction cycle, the overall conversion is about 90% for all tested substrates, with an aldehyde production ranging between 100 and 270 mg depending on the substrate used. As a proof concept, one of the aldehydes thus produced was successfully used for the biomimetic synthesis of a non-natural benzylisoquinoline alkaloid. 相似文献