Synthesis of new pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs as DYRK1A inhibitors

International audienceNew pyridazino[4,5-b]indol-4-ones and pyridazin-3(2H)-one analogs were synthesized and their inhibitory activities against DYRK1A, CDK5/p25, GSK3α/β and p110-α isoform of PI3K evaluated using harmine as reference. Both furan-2-yl 10 and pyridin-4-yl 19 from the two different series, exhibited submicromolar IC50 against DYRK1A with no activities against the three other kinases. In addition, compound 10 exhibited antiproliferative activities in the Huh-7, Caco2 and MDA-MB-231 cell lines

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Photocontrolled and Post-Polymerisation Functionalisation Routes to Polyferrocenylsilane Homopolymers and Block Copolymers

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Non-Centrosymmetric Cylindrical Block Copolymer Micelles by Unidirectional Growth

Unidirectional Growth Block copolymers, in which two dissimilar polymers are covalently joined together, can be designed to form micelles in solution and can be used as self-assembling injectable gels for tissue engineering or wound healing. One challenge is to find ways to create asymmetrical structures, because normally, block addition would occur at both ends of the polymer chain. Rupar et al. (p. 559 ; see the Perspective by Pochan ) devised a route to link together three diblock copolymers with a capping approach. Protecting one end during growth gave rise to asymmetrical structures. </jats:p

Liquid-based growth of polymeric carbon nitride layers and their use in a mesostructured polymer solar cell with Voc exceeding 1 V

Herein we report a general liquid-mediated pathway for the growth of continuous polymeric carbon nitride (C₃N₄) thin films. The deposition method consists of the use of supramolecular complexes that transform to the liquid state before direct thermal condensation into C₃N₄ solid films. The resulting films exhibit continuous porous C₃N₄ networks on various substrates. Moreover, the optical absorption can be easily tuned to cover the solar spectrum by the insertion of an additional molecule into the starting complex. The strength of the deposition method is demonstrated by the use of the C₃N₄ layer as the electron acceptor in a polymer solar cell that exhibits a remarkable open-circuit voltage exceeding 1 V. The easy, safe, and direct synthesis of carbon nitride in a continuous layered architecture on different functional substrates opens new possibilities for the fabrication of many energy-related devices