ABSTRACT
Missense mutations in EGFR's catalytic domain alter its function, promoting cancer. SEIRA spectroscopy, supported by MD simulations, reveals structural differences in the compactness and hydration of helical motifs between active and inactive EGFR conformations models. These findings provide novel insights into the biophysical mechanisms driving EGFR activation and drug resistance, offering a robust method for studying emerging EGFR mutations and their structural impacts on TKIs' efficacy.
ABSTRACT
The main proteases Mpro are a group of highly conserved cysteine hydrolases in ß-coronaviruses. They have been demonstrated to play an unavoidable role in viral replication, and consequently they have been suggested as key targets for treating coronavirus-caused infectious diseases, mainly from the COVID-19 epidemic. Since the most functional form for Mpro enzymatic activity is associated to its homodimer, compounds inhibiting dimerization should also inhibit catalytic activity. We show how PIR-SEIRA (Plasmonic Internal Reflection-Surface Enhanced InfraRed Absorption) spectroscopy can be a noteworthy technique to study proteins subtle structural variations associated to inhibitor binding. Nanoantennas arrays can selectively confine and enhance electromagnetic field via localized plasmonic resonances, thus promoting ultrasensitive detection of biomolecules in close proximity of nanoantenna arrays and enabling the effective investigation of protein monolayers. By adopting this approach, reflection measurements conducted under back illumination of nanoantennas allow to probe anchored protein monolayers, with minimum contribution of environmental buffer molecules. PIR-SEIRA spectroscopy on Mpro was carried out by ad hoc designed devices, resonating in the spectral region of Amide I and Amide II bands. We evaluated here the structure of anchored monomers and dimers in different buffered environment and in presence of a newly designed Mpro inhibitor. Experimental results show that dimerization is not associated to relevant backbone rearrangements of the protein at secondary structure level, and even if the compound inhibits the dimerization, it is not effective at breaking preformed dimers.
ABSTRACT
Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.
ABSTRACT
As a result of their coherent interaction, two-dimensional periodic arrays of metallic nanostructures support collective modes commonly known as lattice resonances. Among them, out-of-plane lattice resonances, for which the nanostructures are polarized in the direction perpendicular to the array, are particularly interesting since their unique configuration minimizes radiative losses. Consequently, these modes present extremely high quality factors and field enhancements that make them ideal for a wide range of applications. However, for the same reasons, their excitation is very challenging and has only been achieved at oblique incidence, which adds a layer of complexity to experiments and poses some limitations on their usage. Here, we present an approach to excite out-of-plane lattice resonances in bipartite arrays under normal incidence. Our method is based on exploiting the electric-magnetic coupling between the nanostructures, which has been traditionally neglected in the characterization of arrays made of metallic nanostructures. Using a rigorous coupled dipole model, we demonstrate that this coupling provides a general mechanism to excite out-of-plane lattice resonances under normal incidence conditions. We complete our study with a comprehensive analysis of a potential implementation of our results using an array of nanodisks with the inclusion of a substrate and a coating. This work provides an efficient approach for the excitation of out-of-plane lattice resonances at normal incidence, thus paving the way for the leverage of the extraordinary properties of these optical modes in a wide range of applications.
ABSTRACT
Metasurfaces are a class of two-dimensional artificial resonators, creating new opportunities for strong light-matter interactions. One type of nonradiative optical metasurface that enables substantial light concentration is based on quasi-Bound States in the Continuum (quasi-BIC). Here we report the design and fabrication of a quasi-BIC dielectric metasurface that serves as an optical frequency antenna for photocatalysis. By depositing Ni nanoparticle reactors onto the metasurface, we create an antenna-reactor photocatalyst, where the virtually lossless metasurface funnels light to drive a chemical reaction. This quasi-BIC-Ni antenna-reactor drives H2 dissociation under resonant illumination, showing strong polarization, wavelength, and optical power dependencies. Both E-field-induced electronic and photothermal heating effects drive the reaction, supported by load-dependent reactivity studies and our theoretical model. This study unlocks new opportunities for photocatalysis that employ dielectric metasurfaces for light harvesting in an antenna-reactor format.