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Failure to resolve inflammation underlies many prevalent pathologies. Recent insights have identified lipid mediators, typified by lipoxins (LXs), as drivers of inflammation resolution, suggesting potential therapeutic benefit. We report the asymmetric preparation of novel quinoxaline-containing synthetic-LXA4-mimetics (QNX-sLXms). Eight novel compounds were screened for their impact on inflammatory responses. Structure–activity relationship (SAR) studies showed that (R)-6 (also referred to as AT-02-CT) was the most efficacious and potent anti-inflammatory compound of those tested. (R)-6 significantly attenuated lipopolysaccharide (LPS)- and tumor-necrosis-factor-α (TNF-α)-induced NF-κB activity in monocytes and vascular smooth muscle cells. The molecular target of (R)-6 was investigated. (R)-6 activated the endogenous LX receptor formyl peptide receptor 2 (ALX/FPR2). The anti-inflammatory properties of (R)-6 were further investigated in vivo in murine models of acute inflammation. Consistent with in vitro observations, (R)-6 attenuated inflammatory responses. These results support the therapeutic potential of the lead QNX-sLXm (R)-6 in the context of novel inflammatory regulators.

This is the accepted manuscript version of the work published in its final form as Fernandez, M. A. G., Marllon Nascimento de Oliveira., Zanetti, A., Schwertz, G., Cossy, J., & Amara, Z. (2021). Photochemical Hydrothiolation of Amorphadiene and Formal Synthesis of Artemisinin via a Pummerer Rearrangement.Organic Letters,23(15), 5593-5598. https://doi.org/10.1021/acs.orglett.1c00636 Deposited byshareyourpaper.organdopenaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailinghelp@openaccessbutton.org.

This is the accepted manuscript version of the work published in its final form as Zanetti, A., Schwertz, G., Marllon Nascimento de Oliveira., Fernandez, M. A. G., Amara, Z., & Cossy, J. (2021). Palladium-Catalyzed Regioselective Allylic Oxidation of Amorphadiene, a Precursor of Artemisinin.The Journal of Organic Chemistry,86(11), 7603-7608. https://doi.org/10.1021/acs.joc.1c00653 Deposited byshareyourpaper.organdopenaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailinghelp@openaccessbutton.org.

Existen muchas definiciones de lo que significa innovación e innovación educativa, pero lo que es necesario rescatar es que la innovación educativa tiene como objetivo primordial alcanzar la calidad de la educación en todos los niveles, especialmente en la Formación por Competencias. La necesidad detectada y que aborda este trabajo es por un lado, la formación de profesionales en Competencias tanto técnicas como sociales, y la propuesta de innovación educativa que las Instituciones Universitarias deben respaldar e implementar en sus carreras con todo el cambio organizacional, estratégico y operativo que esto conlleva. Los Laboratorios Remotos se pueden considerar una innovación educativa ya que le agregan instrumentación, control y acceso a equipos de laboratorio reales sumado a tener una adecuada formación general y por Competencias que les permita adquirir conocimientos y herramientas derivados del avance de la ciencia y de la tecnología. El Proyecto de una Red Argentina colaborativa de Laboratorios de acceso remoto potencia el desarrollo de ecosistemas de experimentación académica que invita a cada institución que forma parte de la Red se especialice en desarrollar una o un grupo de experiencias remotas que se ofrecerán y serán articuladas en un servicio Web.

International audience; A formal synthesis of artemisinin starting from amorphadiene is described. This new route relies on the development of a catalytic chemo-and diastereoselective hydrosilylation. The practicability of this method is demonstrated by converting amorphadiene to dihydroartemisinic aldehyde using a one-pot hydrosilylation/oxidation sequence, minimizing the number of purifications and maximizing the productivity through a practical one-pot procedure. In addition, this approach can be coupled with a crystallization-induced diastereoselective transformation (CIDT) to enhance the optical purity of the key target intermediate, dihydroartemisinic aldehyde.

International audience; Artemisinin is an important drug to fight malaria. It is produced either by extraction or via a semisynthetic route involving enzyme engineering. A key intermediate to produce artemisinin by the enzymatic route is dihydroartemisinic aldehyde (DHAAl). However, control of the absolute configuration of the stereocenter α to the aldehyde is highly challenging. Herein we report a protocol that allows the diastereomeric enrichment of a mixture of (11R)/(11S)-DHAAl to the desired (11R)-DHAAl by utilizing a crystallization-induced diastereomer transformation induced by the Betti base. In addition, the Betti base can be quantitatively recovered and reused after the reaction.

The constant quest of low production cost and short time-to-market, together with the growing complexity of integrated circuits led to the globalization of the supply chain of silicon devices. One of the threats related to such a supply chain are Hardware Trojan Horses (HWTs), that, in the last years, became a serious issue not only for academy but also for industry. Although a large number of methodologies for HWTs prevention, detection and tolerance have been proposed, there is a lack of well-recognized methods and metrics to evaluate their effectiveness. In this paper we present HATE 1, a HArdware Trojan Emulation Environment. The goal of HATE is twofold: (i) the tool can be used to analyse whether a given HWT (or a given set of HWTs) is activated by a software running on a microprocessor, and (ii) it can be used to assess HWTs detection techniques in microprocessors against a set of generated HWTs (either randomly or not). HATE represents, in our vision, a step towards the definition of a reference benchmarking scenario, to provide a comparative ground for evaluating different proposals focusing on HWT detection/tolerance. A subset of MiBench programs have been used to analyse the efficiency of HATE.1HATE is freely available at http://cassano.faculty.polimi.it/

Amorphadiene is a natural product involved in the biosynthesis of the antimalarial drug artemisinin. A convenient four-step synthesis of amorphadiene, starting from commercially available dihydroartemisinic acid, is reported. The targeted molecule is isolated with an overall yield of 85% on a multi-gram scale in four steps with only one chromatography., Graphical abstract Image 1, Highlights • A direct method for the production of amorpha-4,11-diene. • The multi-step sequence is high yielding, scalable and reproducible. • The multi-step sequence involves only one chromatography. • The last step is accelerated using microwave irradiation.

El Aprendizaje centrado en el alumno no concibe la Evaluación como una tarea exclusiva del Profesor, asumir que la Evaluación es parte del proceso de formación conduce a considerar la participación de los estudiantes en el mismo. El presente trabajo tiene por objetivo presentar una propuesta de trabajo colaborativo (docente-alumnos) para el armado de rúbricas de evaluación en el contexto de un trabajo integrador de cátedra obligatorio para la evaluación de ciertos Resultados de Aprendizaje como parte de un Modelo de Formación por Competencias. El trabajo colaborativo es un modelo centrado en el alumno que tiene como fundamento el consenso a partir de la interacción de las partes; la autoridad y responsabilidad es compartida, y el grupo posee la flexibilidad necesaria para buscar la información extra necesaria para lograr el objetivo en común. La metodología utilizada es mixta, cualitativa y cuantitativa. Los resultados obtenidos son más satisfactorios que en evaluaciones anteriores y los alumnos manifestaron interés en participar del armado de una rúbrica de evaluación para uso del trabajo práctico integrador.

Lipoxins (LXs) are endogenously generated eicosanoids with potent bio-actions consistent with attenuation of inflammation. The costly synthesis and metabolic instability of LXs may limit their therapeutic potential. Here we report the synthesis and characterization of novel imidazole-/oxazole-containing synthetic-LX-mimetics (sLXms). The key steps of asymmetric synthesis of putative sLXms include a Suzuki reaction and an asymmetric ketone reduction. The effect of the novel compounds on inflammatory responses was assessed using a human monocyte cell line stably expressing a Nuclear Factor Kappa B (NFkB) reporter gene, by investigating downstream cytokine secretion. The potential interaction of the imidazoles/oxazoles with the molecular target of LXs, i.e. G-protein coupled receptor (GPCR) Formyl Peptide Receptor 2 (ALX/FPR2) was investigated using a cell system where ALX/FPR2 is coupled to the Gα

Mesenchymal stem cells (MSCs) have been extensively explored in a variety of regenerative medicine applications. The relatively large size of MSCs expanded in tissue culture flasks leads to retention in the microcirculation of the lungs following intravenous delivery, reducing their capacity to reach target sites. We explored whether the expansion of whole marrow in suspension cultures would yield smaller MSCs with increased capacity to traverse the pulmonary microcirculation compared with traditional monolayer cultures. We tested this hypothesis using rat marrow in a suspension bioreactor culture with fibronectin-coated microcarriers, leading to sustained expansion of both the microbead-adherent cells, as well as of a nonadherent cell fraction. Magnetic depletion of CD45(+) cells from the bioreactor cultures after 5 weeks led to a highly enriched CD73(+)/CD90(+)/CD105(+) MSC population. The bioreactor-grown MSCs were significantly smaller than parallel monolayer MSCs (15.1 ± 0.9 μm vs. 18.5 ± 2.3 μm diameter, p0.05). When fluorescently labeled bioreactor-grown MSCs were intravenously injected into rats, the peak cell concentration in the arterial circulation was an order of magnitude higher than similarly delivered monolayer-grown MSCs (94.8 ± 29.6 vs. 8.2 ± 5.6/10(6) nucleated blood cells, respectively, p0.05). At 24 h after intravenous injection of the LacZ-labeled bioreactor-grown MSCs, there was a significant threefold decrease in the LacZ-labeled MSCs trapped in the lungs, with a significant increase in the cells reaching the spleen and liver in comparison to their monolayer MSC counterparts. Bioreactor-grown whole marrow cell cultures yielded smaller MSCs with increased capacity to traverse the pulmonary microcirculation compared with traditionally expanded monolayer MSCs. This may significantly improve the capacity and efficiency of these cells to home to injury sites downstream of the lungs.

This paper presents a review of the reconstruction results obtained from the inversion of experimental data provided by the Institute Fresnel in Marseille (France) and concerned with inhomogeneous dielectric tergets and hybrid configurations, where dielectric and metallic cylinders are present in the scenario under test.

Lipoxins (LXs) are endogenously generated eicosanoids with potent bio-actions consistent with attenuation of inflammation. The costly synthesis and metabolic instability of LXs may limit their therapeutic potential. Here we report the synthesis and characterization of novel imidazole-/oxazole-containing synthetic-LX-mimetics (sLXms). The key steps of asymmetric synthesis of putative sLXms include a Suzuki reaction and an asymmetric ketone reduction. The effect of the novel compounds on inflammatory responses was assessed using a human monocyte cell line stably expressing a Nuclear Factor Kappa B (NFkB) reporter gene, by investigating downstream cytokine secretion. The potential interaction of the imidazoles/oxazoles with the molecular target of LXs, i.e. G-protein coupled receptor (GPCR) Formyl Peptide Receptor 2 (ALX/FPR2) was investigated using a cell system where ALX/FPR2 is coupled to the Gαq subunit and receptor interaction determined by mobilisation of intracellular calcium. In vivo anti-inflammatory effects were assessed using a murine zymosan-induced peritonitis model. Overall, structure-activity relationship (SAR) studies demonstrated that the (R)-epimer of 6C-dimethyl-imidazole (1R)-11 was the most potent and efficient anti-inflammatory agent, among the ten compounds tested. This molecule significantly attenuated LPS-induced NFkB activity, reduced the release of several pro-inflammatory cytokines and inhibited peritonitis-associated neutrophil infiltration in vivo. The underlying mechanism for those actions appeared to be through FPR2 activation. These data support the therapeutic potential of imidazole-containing sLXms in the context of novel inflammatory regulators.