Suchergebnisse

The development of advanced piezoelectric α‐quartz microelectromechanical system (MEMS) for sensing and precise frequency control applications requires the nanostructuration and on‐chip integration of this material on silicon material. However, the current quartz manufacturing methods are based on bonding bulk micromachined crystals on silicon, which limits the size, the performance, the integration cost, and the scalability of quartz microdevices. Here, chemical solution deposition, soft‐nanoimprint lithography, and top‐down microfabrication processes are combined to develop the first nanostructured epitaxial (100)α‐quartz/(100)Si piezoelectric cantilevers. The coherent Si/quartz interface and film thinness combined with a controlled nanostructuration on silicon–insulator–silicon technology substrates provide high force and mass sensitivity while preserving the mechanical quality factor of the microelectromechanical systems. This work proves that biocompatible nanostructured epitaxial piezoelectric α‐quartz‐based MEMS on silicon can be engineered at low cost by combining soft‐chemistry and top‐down lithographic techniques. ; This project had received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project SENSiSOFT No.803004). L.P. acknowledges the ATIP–Avenir program for financial support. The authors thank C. André for providing the transfected HT1080 cell line and C. Cazevielle (MRI‐COMET, Montpellier) for assistance with biological SEM images. The authors thank D. Montero for performing the FEG–SEM images and chemical analysis. The FEG–SEM instrumentation was facilitated by the Institut des Matériaux de Paris Centre (Grant No. IMPC FR2482) and was funded by Sorbonne Université, CNRS and by the C'Nano projects of the Région Ile‐de‐France. The authors thank Frederic Pichot, David Bourrier, and Guilhem Larrieu for the expertise and advice during the cantilever lithographic processes. The authors also thank Wioletta Trzpil, Frank Augereau, and Eric Rosenkrantz for the advice during vibrometry measurements. A.G and M.G acknowledge funding from the Spanish Ministerio de Ciencia e Innovacion through the severo Ochoa program (CEX2019‐000917‐S). ; Peer reviewed

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19. ; This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N Izquierdo-Useros has nonrestrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. NJ Krogan was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between the University of California, San Francisco (UCSF), University of California, Berkley (UCB), and GlaxoSmithKline (GSK) (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by Center for Research for Influenza Pathogenesis and Transmission (CRIPT), a National Institute of Allergy and Infectious Diseases (NIAID) supported Center of Excellence for Influenza Research and Response (CEIRS, contract # 75N93021C00014), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972, and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to A García-Sastre. S Yildiz received funding from a Swiss National Foundation Early Postdoc Mobility fellowship (P2GEP3_184202). ; Peer reviewed