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In order to assess whether previous hepatic IR (Hepatic-IRfasting) and beta-cell functionality could modulate type 2 diabetes remission and the need for starting glucose-lowering treatment, newly-diagnosed type 2 diabetes participants who had never received glucose-lowering treatment (190 out of 1002) from the CORDIOPREV study (a prospective, randomized and controlled clinical trial), were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was defined according to the ADA recommendation for levels of HbA1c, fasting plasma glucose and 2h plasma glucose after OGTT, and having maintained them for at least 2 consecutive years. Patients were classified according to the median of Hepatic-IRfasting and beta-cell functionality, measured as the disposition index (DI) at baseline. Cox proportional hazards regression determined the potential for Hepatic-IRfasting and DI indexes as predictors of diabetes remission and the probability of starting pharmacological treatment after a five-year follow-up. Low-Hepatic-IRfasting or high-DI patients had a higher probability of diabetes remission than high-Hepatic-IRfasting or low-DI subjects (HR:1.79;95%CI 1.06-3.05; and HR:2.66;95%CI 1.60-4.43, respectively) after a dietary intervention with no pharmacological treatment and no weight loss. The combination of low-Hepatic-IRfasting and high-DI presented the highest probability of remission (HR:4.63;95%CI 2.00-10.70). Among patients maintaining diabetes, those with high- Hepatic-IRfasting and low-DI showed the highest risk of starting glucose-lowering therapy (HR:3.24;95%CI 1.50-7.02). Newly-diagnosed type 2 diabetes patients with better beta-cell functionality and lower Hepatic-IRfasting had a higher probability of type 2 diabetes remission in a dietary intervention without pharmacological treatment or weight loss, whereas among patients not achieving remission, those with worse beta-cell functionality and higher Hepatic-IRfasting index had the highest risk of starting glucose-lowering treatment after five years of follow-up. BACKGROUND: Our current knowledge regarding the etiology of type 2 diabetes points to hepatic insulin resistance and beta cell functionality as two major abnormalities underlying the disease. Previous studies have associated type 2 diabetes remission with weight loss, together with a decrease in liver fat content and a higher beta cell recovery. TRANSLATIONAL SIGNIFICANCE: Patients with lower hepatic insulin resistance and better beta cell functionality had a higher probability of remission without significant weight loss or pharmacological treatment. These results suggest that clinicians could identify patients with specific phenotypes in early-diagnosed type 2 diabetes that could be the key to achieve higher remission rates without weight loss or pharmacological treatment.

The surface morphology of the materials is known to have significant influence on the overall photocatalytic performance. Therefore, identifying the corresponding electronic structures associated with the surface redox centers is essential for the rational design of Ag2O-based photocatalysts. In this study, comprehensive and systematic theoretical calculations revealed the connection between electronic structure and morphology responsible for the photo-induced mechanism. First-principles calculations showed that the activity of Ag+ cations on the exposed surfaces is dependent of their local coordination and electronic configuration. Electrons were found to migrate to the energetically favorable (1 1 1) surface, while holes are concentrated in the more unstable (1 0 0) and (1 1 0) surfaces. The complete set of available morphologies was obtained, enabling us to rationalize the photocatalytic activity in terms of composition, geometry, and electronic structure of the exposed surfaces. Moreover, the localization and characterization of excited electronic states of both bulk material and exposed surfaces allow us to discuss the fundamental reactions involved in the photocatalytic mechanism underlying the morphological evolution and would promote significantly the development and application of singlet-triplet mechanism. The detailed insights provided by our work could benefit the design and preparation of new efficient photocatalysts based on Ag2O.

This work was supported by Grants from Comisi´on Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (SAF2017-84894-R), Junta de Andalucía (CTS-164) with funds from the European Union, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV), Spain. M.T. is a postdoctoral fellow of Instituto de Salud Carlos III (Sara Borrell Program). I.R.-V. is a predoctoral fellow of MINECO. The cost of this publication was paid in part with funds from the European Union (Fondo Europeo de Desarrollo Regional, FEDER, “FEDER una manera de hacer Europa”)., Microbiota has a role in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzes whether MMF improves dysbiosis in a genetic model of hypertension. Twenty weeks old male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were randomly divided into three groups: untreated WKY, untreated SHR, and SHR treated with MMF for 5 weeks. MMF treatment restored gut bacteria from the phyla Firmicutes and Bacteroidetes, and acetate- and lactate-producing bacteria to levels similar to those found in WKY, increasing butyrate-producing bacteria. MMF increased the percentage of anaerobic bacteria in the gut. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. MMF increased the lower regulatory T cells proportion in mesenteric lymph nodes and Th17 and Th1 infiltration in aorta, improved aortic endothelial function and reduced systolic BP. This study demonstrates for the first time that MMF reduces gut dysbiosis in SHR. This effect could be related to its capability to improve gut integrity due to reduced sympathetic drive in the gut associated to the reduced brain neuroinflammation., Comision Interministerial de Ciencia y Tecnologia, Ministerio de Economia y competitividad SAF201784894R, Junta de Andalucia CTS-164, European Commission, Spanish Government, Instituto de Salud Carlos III (CIBERCV) , Spain, European Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa")

[EN] We propose new local error estimators for splitting and composition methods. They are based on the construction of lower order schemes obtained at each step as a linear combination of the intermediate stages of the integrator, so that the additional computational cost required for their evaluation is almost insignificant. These estimators can be subsequently used to adapt the step size along the integration. Numerical examples show the efficiency of the procedure., Part of this work was developed during a research stay at the Wolfgang Pauli Institute Vienna; the authors are grateful to the director Norbert Mauser and the staff members for their support and hospitality. The first two authors acknowledge funding by the Ministerio de Economia y Competitividad (Spain) through project MTM2016-77660-P (AEI/FEDER, UE).

International audience; The present join experimental and theoretical work provides in-depth understanding on the relationship among structural, optical, and electronic properties and photocatalytic activity of Ag3PO4:Mo microcrystals. We prepared Ag3PO4 and (Mo-doped) Ag3PO4:Mo microcrystals using the chemical precipitation method. The as-synthetized samples have been characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy, transmission electron microscopy, high angle annular dark field scanning transmission electron microscopy (HAADF-STEM), energy-dispersive X-ray spectroscopy (EDS) techniques, and photoluminescence (PL) emission. Density functional theory calculations have been performed to complement the experimental results and understand the physical phenomena taking place in the structure, electronic and optical properties involved in the Mo doping process on the Ag3PO4, and consequently the photocatalytic performances of these new materials. XRD analysis showed that at a doping level below 2% the samples did not present any secondary phases, demonstrating that the Mo cations have been actually incorporated in the Ag3PO4 structure. Moreover, HAADF-STEM and EDS mapping showed that the samples were homogeneous, especially with respect to the Mo cations, and showed no signs of segregation. The Egap value and PL measurements indicated that the doping process caused structural defects in the Ag3PO4 structure. The photocatalytic activity of both the pure and Mo-doped materials was tested for the degradation of Rhodamine B under visible light irradiation. The results demonstrated that the sample of Ag3PO4:Mo with 0.5% Mo had a faster degradation rate, approximately 92% after 5 min of irradiation, while the degradation rate of the pure sample was only 46% during the same time.

Two distinct series of the 3-amino-1,5-benzoxathiepin scaffold, derived from L-cysteine, were synthesized and evaluated for their anti-proliferative activity in the breast cancer MDA-MB-231 and MCF-7 cells, and in the ovarian carcinoma SKOV-3 cell line. (3R)-Amino-3,4-dihydro-2H-1,5-benzoxathiepin [(R)-10] was diversified into two forms: (a) by incorporating different amino acids at its position 3, through an amide bond; and (b) by construction of the purine ring to give 6-chloro-9-[2-(3,4-dihydro-2H-1,5-benzoxathiepin-(3R)-yl)]-9H-purine [(R)-28]. Nevertheless, when the introduction of iodine was tried at position 2 of the purine ring of (R)-28, 2-{[2-(6-chloro-2-iodo-9H-purin-9-yl)prop-2-en-1-yl]thio}phenol (34) was obtained. Compound 34 shows activity against cancer cells. Interestingly, 34 inhibits mammosphere formation at the micromolar range, demonstrating activity against cancer stem cells. Although further studies of its targets and mechanism of action are needed, these findings support the therapeutic potential of this compound in cancer., We thank the Ministerio de Economía y Competitividad (grant CTQ2013-40855-R), Gobierno de Aragón–Fondo Social Europeo (research group E40), and the Intramural CSIC (201530E011) for providing X-ray structural facilities for this work.

[Background] Deep Brain Stimulation (DBS) of the subgenual cingulate cortex (SCC) is a promising therapeutic alternative to treat resistant major depressive disorder. In preclinical studies, DBS of the ventromedial prefrontal cortex (vmPFC, the rodent SCC correlate) provokes an antidepressant-like effect, along with changes in noradrenaline levels at the site of stimulation. Hence, DBS appears to activate the noradrenergic-locus coeruleus (LC) system., [Objective/Hypothesis] The aim of this study was to evaluate the effect of vmPFC DBS on the electrical activity of noradrenergic LC neurons, cortical oscillations and coherence between both brain areas in male rats., [Methods] The antidepressant-like effect of vmPFC DBS was evaluated through the forced swimming test. Tonic and evoked activity of LC neurons, LC activity of alpha2-adrenoceptors, local field potentials from LC and electrocorticogram signals were studied after DBS by electrophysiological recordings in anaesthetized rats. The effect of DBS on tyrosine hydroxylase (TH), noradrenaline transporters (NAT), phosphorylation of the extracellular signal–regulated kinase (ERK) and corticotropin releasing factor (CRF) expression in the LC were measured by western blot assays., [Results] DBS induced an antidepressant-like effect increasing climbing behaviour in the FST that was accompanied by a robust increase of TH expression in the rat LC. The tonic and evoked activity of LC neurons was enhanced by DBS, which impaired alpha2-adrenoceptors activity. DBS also promoted an increase in slow LC oscillations, as well as a shift in LC-cortical coherence., [Conclusion] DBS of the vmPFC appears to affect the LC, producing changes that may underlie its antidepressant-like effects., This work was supported by grants from the “Ministerio de Economía y Competitividad” (MINECO) co-financed by “Fondo Europeo de Desarrollo Regional” FEDER “A way to build Europe” (SAF2015-68647-R; “Instituto de Salud Carlos III” (PI12/00915; PI16/00287)); the “Centro de Investigacion Biomedica en Red de Salud Mental-CIBERSAM” (Spain; G18, G02); the “Consejería de Economía, Innovacion, Ciencia y Empleo de la Junta de Andalucía ” (Spain; CTS-510 and CTS-7748); a 2015 NARSAD Young Investigator Grant from the Brain Behavior Research Foundation (NARSAD 23982); and a FPI fellowship (2011-145).

Metalloporphyrins exhibit outstanding chemical, physical and biological properties in dissolution, however, it is a challenge to synthesize them as stable solid frameworks. Long-time stability is crucial for future applications of these materials, and we have detected a slow, solid-state transformation of a 2D MnII-porphyrin at RT. The remarkable point is that this transformation showed up as a result of Electronic Paramagnetic Resonance measurements. Otherwise, the evolution of the system could have remained undetected. Thus, 2D [Mn3(TCPP)(H2O)4]•nD (1) (where TCPP is meso-tetra(4-carboxyphenyl)porphyrin and D is the sovent) has been synthesized hydrothermally, and characterised by means of X-ray diffraction (XRD), Thermogravimetry and X-ray thermodiffractometry (XRTD). This compound slowly transforms into [Mn(H4TCPP)(H2O)2]•nD (2) according to the equilibrium [Mn3(TCPP)]+4H+ ↔ [Mn(H4TCPP)]+2Mn2+. The evolution of the system has been studied through analysis of the distortion (both of the coordination sphere and the tetrapyrrolic macrocycle) and Density Functional Theory (DFT) quantum mechanical calculations. Ministerio de Economia y Competitividad (MAT2013-42092-R), Gobierno Vasco (Basque University System Research Groups, IT-630-13) and UPV/EHU (UFI11/15)

International audience; In this paper we present a high-order density-based finite-volume framework for all-speed flows. The formulation is based on high-order variable reconstructions performed using Moving Least Squares approximations. In particular, we show that combining high-order discretization schemes with low-Mach fixes, it is possible to remove the grid dependency problem at low Mach numbers on both structured and unstructured grids. In order to maintain the accuracy and the robustness of the numerical method at transonic conditions, different procedures are proposed, based on the use of a selective limiting.

International audience; Transmissible spongiform encephalopaties (TSEs) are fatal neurodegenerative diseases characterized by the aggregation and accumulation of the misfolded prion protein in the brain. Other proteins such as beta-amyloid, tau or Serum Amyloid-A (SAA) seem to share with prions some aspects of their pathogenic mechanism; causing a variety of so called prion-like diseases in humans and/or animals such as Alzheimer's, Parkinson's, Huntington's, Type II diabetes mellitus or amyloidosis. The question remains whether these misfolding proteins have the ability to self-propagate and transmit in a similar manner to prions. In this review, we describe the prion and prion-like diseases affecting animals as well as the recent findings suggesting the prion-like transmissibility of certain non-prion proteins.

Nanoparticles with different morphologies were added to water to study if the morphology of the nanoparticles affects the main parameters of water used as phase change material (PCM). Considered morphologies were spherical, tubes and sheets in the form of spherical carbon black nanoparticles (CB), multiwalled carbon nanotubes (MWCNT), and graphene oxide nanosheets (GO). Results demonstrate that effectively the morphology of nanoparticles affect the thermophysical properties of the nano-enhanced PCM (NePCM). Depending on the morphology of the added nanoparticle, the final NePCM will have different subcooling and thermal conductivity, whereas its phase change enthalpy is not affected and, therefore, is the same for all produced NePCM. The research leading to these results has received funding from the European Commission Seventh Framework Programme (FP/2007-2013) under grant agreement n° PIRSES-GA-2013-610692 (INNOSTORAGE) and from the European Union’s Horizon 2020 research and innovation program under grant agreement No 657466 (INPATH-TES). The authors would like to thank the Catalan Government for the quality accreditation given to their research groups GREA (2014 SGR 123), DIOPMA (2014 SGR 1543). This work has been partially funded by the Spanish government (ENE2015-64117-C5-1-R (MINECO/FEDER) and ENE2015-64117-C5-2-R (MINECO/FEDER)). Dr. Camila Barreneche would like to thank Ministerio de Economia y Competitividad de España for Grant Juan de la Cierva FJCI-2014-22886. This work has been developed by participants of the COST Action CA15119 Overcoming Barriers to Nanofluids Market Uptake (NANOUPTAKE).