Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF-C/VEGFR-3 signalling pathway

BACKGROUND AND PURPOSE Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2-methyl-hydroquinone isolated from the culture broth of the marine fungus Penicillium sp. HL-85-ALS5-R004, to inhibit lymphangiogenesis in vitro, ex vivo and in vivo. EXPERIMENTAL APPROACH We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D in vitro cultures and in the ex vivo mouse lymphatic ring assay. For in vivo approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets. KEY RESULTS Toluquinol inhibited LEC proliferation,migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment in vitro, blocked the development of the thoracic duct in zebrafish and reduced the VEGF-C-induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF-C-induced VEGFR-3 phosphorylation in a dose-dependentmanner and suppresses the phosphorylation of Akt and ERK1/2. CONCLUSIONS AND IMPLICATIONS Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis-related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work has been supported by personal funding by FP7-PEOPLE-2013-IEF Marie Curie Postdoctoral Fellowship (MGC). Acknowledged are the supporting grants from the Action de Recherche Concertée (ARC) (Université de Liège), the Fonds de la Recherche Scientifique-FNRS (F.R.S.-FNRS), the Foundation Against Cancer (foundation of public interest), the Centre Anticancéreux près l’Université de Liège, the Fonds Léon Fredericq (University of Liège), the Interuniversity Attraction Poles Programme-Belgian Science Policy (all from Belgium) and the Plan National Cancer (« Service Public Federal » from Belgium). Research in the lab of A.R.Q. and M.A.M. was supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER)

Integration of a voice recognition system in a social robot

Human-Robot Interaction (HRI) 1 is one of the main fields in the study and research of robotics. Within this field, dialog systems and interaction by voice play a very important role. When speaking about human- robot natural dialog we assume that the robot has the capability to accurately recognize the utterance what the human wants to transmit verbally and even its semantic meaning, but this is not always achieved. In this paper we describe the steps and requirements that we went through in order to endow the personal social robot Maggie, developed in the University Carlos III of Madrid, with the capability of understanding the natural language spoken by any human. We have analyzed the different possibilities offered by current software/hardware alternatives by testing them in real environments. We have obtained accurate data related to the speech recognition capabilities in different environments, using the most modern audio acquisition systems and analyzing not so typical parameters as user age, sex, intonation, volume and language. Finally we propose a new model to classify recognition results as accepted and rejected, based in a second ASR opinion. This new approach takes into account the pre-calculated success rate in noise intervals for each recognition framework decreasing false positives and false negatives rate.The funds have provided by the Spanish Government through the project called `Peer to Peer Robot-Human Interaction'' (R2H), of MEC (Ministry of Science and Education), and the project “A new approach to social robotics'' (AROS), of MICINN (Ministry of Science and Innovation). The research leading to these results has received funding from the RoboCity2030-II-CM project (S2009/DPI-1559), funded by Programas de Actividades I+D en la Comunidad de Madrid and cofunded by Structural Funds of the EU

COVID-19 and the Use of Angiotensin II Receptor Blockers in Older Chronic Hypertensive Patients: Systematic Review and Meta-Analysis

Angiotensin II-converting enzyme inhibitors (ACEIs) and selective angiotensin II receptor antagonists (ARAIIs) are widely used antihypertensive agents. Their use has generated controversy due to their possible influence on the health status of chronic patients infected with COVID-19. The objective of this work is to analyze the influence of COVID-19 on chronic hypertensive patients treated with ACEI and ARAII inhibitors. A systematic review and meta-analysis in the databases Pubmed, Pro-Quest and Scopus were carried out. The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search equation descriptors were obtained from the Medical Subject Headings (MeSH) thesaurus. The search equation was: “Older AND hypertension AND (COVID-19 OR coronavirus) AND primary care” and its equivalent in Spanish. Nineteen articles were obtained, with n = 10,806,159 subjects. Several studies describe the COVID-19 association with ACEI or ARAII treatment in hypertension patients as a protective factor, some as a risk factor, and others without a risk association. In the case of ACEI vs. ARAII, the risk described for the former has an odds ratio (OR) of 0.55, and for ARAII, an OR of 0.59. Some authors talk about mortality associated with COVID-19 and ACEI with a half ratio (HR) of 0.97, and also associated ARAIIs with an HR of 0.98. It is recommended to maintain the use of the renin–angiotensin–aldosterone axis in the context of the COVID-19 diseas

Learning to Avoid Risky Actions

When a reinforcement learning agent executes actions that can cause frequent damage to itself, it can learn, by using Q-learning, that these actions must not be executed again. However, there are other actions that do not cause damage frequently but only once in a while, for example, risky actions such as parachuting. These actions may imply punishment to the agent and, depending on its personality, it would be better to avoid them. Nevertheless, using the standard Q-learning algorithm, the agent is not able to learn to avoid them, because the result of these actions can be positive on average. In this article, an additional mechanism of Q-learning, inspired by the emotion of fear, is introduced in order to deal with those risky actions by considering the worst results. Moreover, there is a daring factor for adjusting the consideration of the risk. This mechanism is implemented on an autonomous agent living in a virtual environment. The results present the performance of the agent with different daring degrees.The funds provided by the Spanish Government through the project called “A New Approach to Social Robotics” (AROS), of MICINN (Ministry of Science and Innovation) and through the RoboCity2030-IICM project (S2009/DPI-1559), funded by Programas de Actividades I+D en la Comunidad de Madrid and cofunded by Structural Funds of the EU

Nucleopolyhedrovirus coocclusion technology: a new concept in the development of biological insecticides

Nucleopolyhedroviruses (NPV, Baculoviridae) that infect lepidopteran pests have an established record as safe and effective biological insecticides. Here, we describe a new approach for the development of NPV-based insecticides. This technology takes advantage of the unique way in which these viruses are transmitted as collective infectious units, and the genotypic diversity present in natural virus populations. A ten-step procedure is described involving genotypic variant selection, mixing, coinfection and intraspecific coocclusion of variants within viral occlusion bodies. Using two examples, we demonstrate how this approach can be used to produce highly pathogenic virus preparations for pest control. As restricted host range limits the uptake of NPV-based insecticides, this technology has recently been adapted to produce custom-designed interspecific mixtures of viruses that can be applied to control complexes of lepidopteran pests on particular crops, as long as a shared host species is available for virus production. This approach to the development of NPV-based insecticides has the potential to be applied across a broad range of NPV-pest pathosystems.This review was funded by the Ministerio de Economía y Competitividad, Spain, project number AGL2017-83498-C2-1-R and previous projects AGL2014-57752-C2-1-R, AGL2011-30352-CO2-01, AGL2008-05456-C03-01, AGL2005-07909-CO3-01, and AGL2002-04320-C02-01

IBD and Motherhood: A Journey through Conception, Pregnancy and Beyond

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it’s evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there’s a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes

Inverse cascades sustained by the transfer rate of angular momentum in a 3D turbulent flow

The existence of energy cascades as signatures of conserved magnitudes is one of the universal characteristics of turbulent flows. In homogeneous 3D turbulence, the energy conservation produces a direct cascade from large to small scales, although in 2D, it produces an inverse cascade pointing towards small wave numbers. In this Letter, we present the first evidence of an inverse cascade in a fully developed 3D experimental turbulent flow where the conserved magnitude is the angular momentum. Two counterrotating flows collide in a central region where very large fluctuations are produced, generating a turbulent drag that transfers the external torque between different fluid layers

End-user programming of a social robot by dialog

One of the main challenges faced by social robots is how to provide intuitive, natural and enjoyable usability for the end-user. In our ordinary environment, social robots could be important tools for education and entertainment (edutainment) in a variety of ways. This paper presents a Natural Programming System (NPS) that is geared to non-expert users. The main goal of such a system is to provide an enjoyable interactive platform for the users to build different programs within their social robot platform. The end-user can build a complex net of actions and conditions (a sequence) in a social robot via mixed-initiative dialogs and multimodal interaction. The system has been implemented and tested in Maggie, a real social robot with multiple skills, conceived as a general HRI researching platform. The robot's internal features (skills) have been implemented to be verbally accessible to the end-user, who can combine them into others that are more complex following a bottom-up model. The built sequence is internally implemented as a Sequence Function Chart (SFC), which allows parallel execution, modularity and re-use. A multimodal Dialog Manager System (DMS) takes charge of keeping the coherence of the interaction. This work is thought for bringing social robots closer to non-expert users, who can play the game of "teaching how to do things" with the robot.The research leading to these results has received funding from the RoboCity2030-II-CM project (S2009/DPI-1559), funded by Programas de Actividades I+D en la Comunidad de Madrid and cofunded by Structural Funds of the EU. The authors also gratefully acknowledge the funds provided by the Spanish Ministry of Science and Innovation (MICINN) through the project named “A New Approach to Social Robots” (AROS) DPI2008-01109