Groupe SEB

Small-molecule immune modulators offer a promising alternative to biologics, such as antibodies, for cancer immunotherapy. A key example is the TLR7 agonist imiquimod (IMQ), which has already been approved for the treatment of various dermatological malignancies. Nevertheless, the clinical use of IMQ is limited to tumors amenable to topical application, as its systemic administration poses a high risk of severe inflammatory toxicity due to the widespread expression of TLRs. Therefore, to extend the use of TLR7 agonists to the treatment of other solid tumor types, we developed a β-glucuronidase-responsive albumin-binding prodrug designed for the selective delivery of IMQ within the tumor microenvironment. This prodrug masks IMQ's immunogenicity, allowing for its administration in immunocompetent mice without eliciting the systemic side effects associated with TLR7 agonists. However, the β-glucuronidase-catalyzed prodrug activation enables the selective, tumor site-specific release of IMQ, thereby restoring its biological activities. This controlled delivery promotes M1 macrophage polarization, T cell activation, and an increase in IgG levels exclusively within malignant tissues without affecting the healthy organs that are sensitive to TLR7 agonists. This study demonstrates that targeting tumor microenvironment specificities represents a promising approach for developing selective cancer immunotherapies based on small-molecule immune modulators.

The photoreduction of substituted nitro (hetero)arenes by iPrOH has been achieved in batch and continuous flow chemistry. Good yields of N-(hetero)arylhydroxylamines were obtained when nitrobenzene was substituted by electron-withdrawing groups. The reaction is chemoselective as nitriles, esters, carboxylic acids, ketones, and halides are not reduced. The application of the photoreduction of nitrobenzene to the synthesis of paracetamol was achieved by the acetylation of N-phenylhydroxylamine followed by an original 1,5-rearrangement.

In this study, we described a two-step process involving an efficient visible-light-induced decarboxylative borylation of α- and β-amino redox-active esters with bis(catecholato)diboron, followed by transamination with 1,8-diaminonapthalene (DANH2). A series of boronamides were obtained in moderate to excellent yields in this one-pot procedure. The photochemical process proved to be very efficient even when conducted under flow conditions with shorter reaction durations and scalable synthesis of DAN boronates.

We propose TabSRA, a novel self-explainable, and accurate model for tabular learning. TabSRA is based on SRA (Self-Reinforcement Attention), new attention mechanism that helps to learn an intelligible representation of the raw input data through element-wise vector multiplication. The learned representation is aggregated by a highly transparent function (e.g linear), which produces the final output. Experimental results on synthetic and real-world classification problems show that the proposed TabSRA solution outperforms existing widely used self-explainable models and performs comparably to full complexity state-of-the-art models in term of accuracy while providing a faithful feature attribution. Source code is available at https://github.com/anselmeamekoe/TabSRA.

El trabajo presenta un marco de evaluación de las competencias digitales de los docentes que tuvo como objetivo orientar el diseño de intervenciones de un Programa de Fortalecimiento para el Aula @prende 2.0 de México. El instrumento de medida de esta competencia constó de dos partes. Una parte refirió a la adopción de la tecnología e indagó el uso de dispositivos y programas y su frecuencia. La otra, refirió a los usos en los procesos de enseñanza e indagó los contenidos en el corazón del marco DIGCOMPEDU de la Unión Europea. Se consideró que un uso poco sofisticado desde el punto de vista operativo puede ser oportuno y relevante desde el punto de vista educativo. Es decir, que un uso de las TIC puede ser estratégico en el proceso educativo sin que éste sea especializado o sofisticado desde el punto de vista técnico. Se discuten los resultados en este sentido, así como posibles sesgos derivados de la aplicación del instrumento, de la adecuación al contexto (válido y confiable hasta ahora en países europeos), o del momento de la medición (la pandemia). Para el análisis de las escalas de DIGCOMPEDU se siguió el procedimiento del Escalograma de Guttman.

The worldwide demand for pulse-based products is increasing in the face of climate change, but their acceptability is limited due to the presence of off-flavours. Off-notes contribute to negative perceptions of pulses (beany notes). Volatile compounds belong to a large variety of chemical classes. They are mainly produced from the oxidation of unsaturated free fatty acids and the degradation of amino acids during seed development, storage, and transformation (dehulling, milling, and starch or protein production). This review aims to provide an overview highlighting the identification of these molecules in different pulses, their potential origins, and their impact on perceptions. However, data on odour-active compounds in pulses are sparse, as they are limited to those of two studies on peas and lupins. A better knowledge of the volatile compounds involved in the off-notes and their origins should allow for drawing efficient strategies to limit their impact on overall perception for more acceptable healthy food design.