Study of the effect of the chromophore and nuclearity on the aggregation and potential biological activity of gold(I) alkynyl complexes

The synthesis and characterization of four organometallic gold(I) complexes containing different water soluble phosphanes (TPPTS, PTA and DAPTA) and chromophoric units (4-pyridylethynyl and propargyloxycoumarin) is here reported. The analysis of their absorption and emission spectra led us to attribute their luminescent behavior to the chromophoric organic ligands. Moreover, the presence of the gold(I) metal atom has been observed to be the responsible of an efficient intersystem crossing process responsible for the observed phosphorescence emission. Broad emission bands are observed in most cases due to the formation of organized aggregates in solution in agreement with microscopic characterization. Biological activity of the complexes showed very low effects against tumor cell growth but an inhibitory potency against thioredoxin reductase (TrxR). The missing/low cytotoxic effects could be related to a low bioavailability as determined by atomic absorption spectroscopy. Graphical abstract The synthesis, characterization, aggregation and emissive properties of four organometallic gold(I) complexes containing different water soluble phosphanes and chromophoric units is here reported. Biological activity of the complexes showed very low effects against tumor cell growth but an inhibitory potency against thioredoxin reductase (TrxR

Modification of polyetherimide membranes with ZIFs fillers for CO2 separation

[EN] Flat hybrid membranes composed of polyetherimide (PEI) as matrix and zeolitic imidazolate frameworks (ZIFs) as fillers at concentrations of 10 and 20 wt% were prepared. Apparent permeability coefficient and apparent diffusivity coefficient of gases (CO2 and N-2) for these hybrid membranes (PZIFs) were determined by the "timelag" method. The experimental conditions used were from 25 degrees C to 55 degrees C with pressures of 2, 3 and 5 bar. The PZIFs with fillers of ZIF-8 (PZ-Zn) and ZIF-67 (PZ-Co) showed apparent selectivities (alpha(pa(CO2)/pa(N2))) of 39.6 and 27.5, respectively, higher than the alpha(pa(CO2)/pa(N2)) of the reference membrane PEI, while the membrane with filler of ZIF-Mix (PZ-Zn/Co) showed the lowest alpha(pa(CO2)()/pa(N2)) selectivity of 10.3 in the membrane series (under conditions of 25 degrees C and 2 bar). It is proposed that the selectivity of the membrane series can be attributed to two critical factors: the particle size/distribution ratio in the polymer base and sorption of CO2 at local sites of the bimetallic mixture. On the other hand, gas permeation studies (O-2, CO2 and CH4, and CO2/CH(4 )and CO2/C2H4 mixtures), were carried out in the series of PZIFs membranes. Permeability data were obtained by an isostatic method based on a permeation cell connected in series to a gas chromatograph where the rate of permeated gases was analyzed until a stationary state was reached. The complementary characterization techniques were: scanning electron microscopy, thermogravimetric analysis, and powder X-ray diffraction, which support the existence of the amorphous/crystalline phases of the PZIFs.This research has been supported by the ENE/2015-69203-R project, granted by the Ministerio de Economia y Competitividad (MINECO), Spain; Also authors are grateful to UNAM-DGAPA-PAPIIT projects IG-100185, and IG-114818. This study was partially supported by the CONACyT (Mexico) projects 2013-05-231461 and CB -2014-01-235840.Vega, J.; Andrio, A.; Lemus, A.; Díaz, J.; Del Castillo, L.; Gavara, R.; Compañ Moreno, V. (2019). Modification of polyetherimide membranes with ZIFs fillers for CO2 separation. Separation and Purification Technology. 212:474-482. https://doi.org/10.1016/j.seppur.2018.11.033S47448221

Extracellular fluid viscosity enhances liver cancer cell mechanosensing and migration

The extracellular fluid (ECF) is a crowded environment containing macromolecules that determine its characteristic density, osmotic pressure, and viscosity, which greatly differ between tissues. Precursors and products of degradation of biomaterials enhance ECF crowding and often increase its viscosity. Also, increases in ECF viscosity are related to mucin-producing adenocarcinomas. However, the effect of ECF viscosity on cells remains largely unexplored. Here we show that viscosity-enhancing polymer solutions promote mesenchymal-like cell migration in liver cancer cell lines. Also, we demonstrate that viscosity enhances integrin-dependent cell spreading rate and causes actin cytoskeleton re-arrangements leading to larger cell area, nuclear flattening, and nuclear translocation of YAP and β-catenin, proteins involved in mechanotransduction. Finally, we describe a relationship between ECF viscosity and substrate stiffness in determining cell area, traction force generation and mechanotransduction, effects that are actin-dependent only on ≤ 40 kPa substrates. These findings reveal that enhancing ECF viscosity can induce major biological responses including cell migration and substrate mechanosensing

Assessment of the nano-mechanical properties of healthy and atherosclerotic coronary arteries by atomic force microscopy.

Nano-indentation techniques might be better equipped to assess the heterogeneous material properties of plaques than macroscopic methods but there are no bespoke protocols for this kind of material testing for coronary arteries. Therefore, we developed a measurement protocol to extract mechanical properties from healthy and atherosclerotic coronary artery tissue sections. Young's modulus was derived from force-indentation data. Metrics of collagen fibre density were extracted from the same tissue, and the local material properties were co-registered to the local collagen microstructure with a robust framework. The locations of the indentation were retrospectively classified by histological category (healthy, plaque, lipid-rich, fibrous cap) according to Picrosirius Red stain and adjacent Hematoxylin & Eosin and Oil-Red-O stains. Plaque tissue was softer (p < 0.001) than the healthy coronary wall. Areas rich in collagen within the plaque (fibrous cap) were significantly (p < 0.001) stiffer than areas poor in collagen/lipid-rich, but less than half as stiff as the healthy coronary media. Young's moduli correlated (Pearson's ρ = 0.53, p < 0.05) with collagen content. Atomic force microscopy (AFM) is capable of detecting tissue stiffness changes related to collagen density in healthy and diseased cardiovascular tissue. Mechanical characterization of atherosclerotic plaques with nano-indentation techniques could refine constitutive models for computational modelling

Supramolecular tripodal Au(I) assemblies in water. Interactions with pyrene fluorescent probe

The synthesis of three gold(I) tripodal complexes derived from tripropargylamine and containing the water soluble phosphines PTA (1, 3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza--phosphabicyclo[3.3.1]nonane) and TPPTS (triphenylphosfine-3,3',3''-trisulfonic acid trisodium salt) is here described. The three complexes are observed to give rise to the formation of supramolecular aggregates in water and very long fibers. This property has been analyzed by means of 1H-NMR spectroscopy at different concentrations and SAXS. The results point out the important role of the phosphine moieties as the main enthalpic or entropic contribution in the resulting Gibbs energy of aggregates formation. The tripodal structure of the three complexes together with the presence of gold(I) atoms make them ideal candidates to interact with hydrophobic molecules also in water. For this, the interaction with pyrene in this solvent has been evaluated with successful results in all three complexes. The highest association constant corresponds to 2 as the host. DFT studies indicates the location of pyrene in the tripodal cavity as the most stable conformation. The interaction with pyrene has been additionally studied within cholate hydrogel matrixes pointing out the stability of the resulting host:guest adducts in the different medium

Methodology of the Virtual Reconstruction of Arquitectonic Heritage: Ambassador Vich's Palace in Valencia

The 19th century was disastrous as far as the conservation of architectonic heritage is concerned. The awareness of the importance of preserving monuments that has prevailed since the end of the last century was dazzlingly absent in the previous, leading both to the disappearance of representative heritage works and the plundering of many others. The present study establishes the methodological basis to proceed with the virtual reconstruction of many disappeared architectures, representative of emblematic architectonic typologies. A method based on the combination of deduction and induction allows benchmarks to be created that signify a starting point to which the key and specific elements of each building are later incorporated, from the data extracted from the conserved parts and the graphic, literary and archive documents. The result is the virtual recovery of the general outlines of the architecture: morphology of the plot, volumetry, exterior and interior facades, and the functional layout. The good results obtained in the study of the disappeared Ambassador Vich's Palace, allow the methodology to be extended to the analysis of other similar examples, serving investigators as a tool to carry out an arduous task of deciphering a trail that is increasingly fading with the passing of time.Galiana Agullo, M.; Mas Tomas, MDLA.; Lerma Elvira, C.; Peñalver Martínez, MJ.; Conesa Tejada, S. (2014). Methodology of the Virtual Reconstruction of Arquitectonic Heritage: Ambassador Vich's Palace in Valencia. International Journal of Architectural Heritage. 8(1):94-123. doi:10.1080/15583058.2012.672623S9412381Boix, V. 1979.Historical and topographic Valencia[in Spanish]. Vol. I261 S. A. Printing J. Rius.Estaban Chapapría, J. (2001). Impostación del patio del Embajador Vich en el ex-convento del Carmen (Valencia). Loggia, Arquitectura & Restauración, (12), 26. doi:10.4995/loggia.2001.3605Morrish, S. W., & Laefer, D. F. (2010). Web-Enabling of Architectural Heritage Inventories. International Journal of Architectural Heritage, 4(1), 16-37. doi:10.1080/15583050902731056Lotz, W. 1995.Architecture in Italy 1500–1600 [in Italian]35–37. ed. RizzoliYale University Press.Lourenço, P. B., Peña, F., & Amado, M. (2010). A Document Management System for the Conservation of Cultural Heritage Buildings. International Journal of Architectural Heritage, 5(1), 101-121. doi:10.1080/15583050903318382Vila Ferrer, S. (2001). La recuperación del patio del palacio del Embajador Vich (Valencia). Loggia, Arquitectura & Restauración, (12), 44. doi:10.4995/loggia.2001.3606Zonta, D., Pozzi, M., & Zanon, P. (2008). Managing the Historical Heritage Using Distributed Technologies. International Journal of Architectural Heritage, 2(3), 200-225. doi:10.1080/1558305080206369

Confined Sandwichlike Microenvironments Tune Myogenic Differentiation.

Sandwichlike (SW) cultures are engineered as a multilayer technology to simultaneously stimulate dorsal and ventral cell receptors, seeking to mimic cell adhesion in three-dimensional (3D) environments in a reductionist manner. The effect of this environment on cell differentiation was investigated for several cell types cultured in standard growth media, which promotes proliferation on two-dimensional (2D) surfaces and avoids any preferential differentiation. First, murine C2C12 myoblasts showed specific myogenic differentiation. Human mesenchymal stem cells (hMSCs) of adipose and bone marrow origin, which can differentiate toward a wider variety of lineages, showed again myodifferentiation. Overall, this study shows myogenic differentiation in normal growth media for several cell types under SW conditions, avoiding the use of growth factors and cytokines, i.e., solely by culturing cells within the SW environment. Mechanistically, it provides further insights into the balance between integrin adhesion to the dorsal substrate and the confinement imposed by the SW system

Exploiting the Redox Activity of MIL-100(Fe) Carrier Enables Prolonged Carvacrol Antimicrobial Activity

The design of efficient food contact materials that maintain optimal levels of food safety is of paramount relevance to reduce the increasing number of foodborne illnesses. In this work, we develop a smart composite metal-organic framework (MOF)-based material that fosters a unique prolonged antibacterial activity. The composite is obtained by entrapping a natural food preserving molecule, carvacrol, into a mesoporous MIL-100(Fe) material following a direct and biocompatible impregnation method, and obtaining particularly high payloads. By exploiting the intrinsic redox nature of the MIL-100(Fe) material, it is possible to achieve a prolonged activity against Escherichia coli and Listeria innocua due to a triggered two-step carvacrol release from films containing the carvacrol@MOF composite. Essentially, it was discovered that based on the underlying chemical interaction between MIL-100(Fe) and carvacrol, it is possible to undergo a reversible charge-transfer process between the metallic MOF counterpart and carvacrol upon certain chemical stimuli. During this process, the preferred carvacrol binding site was monitored by infrared, Mössbauer, and electron paramagnetic resonance spectroscopies, and the results are supported by theoretical calculations

High intrapatient variability of tacrolimus exposure associated with poorer outcomes in liver transplantation

Liver transplantation; Tacrolimus; Liver diseasesTrasplante de hígado; Tacrolimús; Enfermedades del hígadoTrasplantament hepàtic; Tacrolimús; Malalties del fetgeTacrolimus (TAC) is a dose-dependent immunosuppressor with considerable intrapatient variability (IPV) in its pharmacokinetics. The aim of this work is to ascertain the association between TAC IPV at 6 months after liver transplantation (LT) and patient outcome. This single-center cohort study retrospectively analyzed adult patients who underwent transplantation from 2015 to 2019 who survived the first 6 months with a functioning graft. The primary end point was the patient’s probability of death and the secondary outcome was the loss of renal function between month 6 and the last follow-up. TAC IPV was estimated by calculating the coefficient of variation (CV) of the dose-corrected concentration (C0/D) between the third and sixth months post-LT. Of the 140 patients who underwent LT included in the study, the low-variability group (C0/D CV < 27%) comprised 105 patients and the high-variability group (C0/D CV ≥ 27%) 35 patients. One-, 3-, and 5-year patient survival rates were 100%, 82%, and 72% in the high-variability group versus 100%, 97%, and 93% in the low-variability group, respectively (p = 0.005). Moreover, significant impaired renal function was observed in the high-variability group at 1 year (69 ± 16 ml/min/1.73 m2 vs. 78 ± 16 ml/min/1.73 m2, p = 0.004) and at 2 years post-LT (69 ± 17 ml/min/1.73 m2 vs. 77 ± 15 ml/min/1.73 m2, p = 0.03). High C0/D CV 3–6 months remained independently associated with worse survival (hazard ratio = 3.57, 95% CI = 1.32–9.67, p = 0.012) and loss of renal function (odds ratio = 3.47, 95% CI = 1.30–9.20, p = 0.01). Therefore, high IPV between the third and sixth months appears to be an early and independent predictor of patients with poorer liver transplant outcomes.Isabel Campos-Varela’s research activity is funded by grant PI19/00330 from Instituto de Salud Carlos III. CIBERehd is supported by Instituto de Salud Carlos III. The work was independent of all funding

Coronary Revascularization and Long-Term Survivorship in Chronic Coronary Syndrome

Ischemic heart disease (IHD) persists as the leading cause of death in the Western world. In recent decades, great headway has been made in reducing mortality due to IHD, based around secondary prevention. The advent of coronary revascularization techniques, first coronary artery bypass grafting (CABG) surgery in the 1960s and then percutaneous coronary intervention (PCI) in the 1970s, has represented one of the major breakthroughs in medicine during the last century. The benefit provided by these techniques, especially PCI, has been crucial in lowering mortality rates in acute coronary syndrome (ACS). However, in the setting where IHD is most prevalent, namely chronic coronary syndrome (CCS), the increase in life expectancy provided by coronary revascularization is controversial. Over more than 40 years, several clinical trials have been carried out comparing optimal medical treatment (OMT) alone with a strategy of routine coronary revascularization on top of OMT. Beyond a certain degree of symptomatic improvement and lower incidence of minor events, routine invasive management has not demonstrated a convincing effect in terms of reducing mortality in CCS. Based on the accumulated evidence more than half a century after the first revascularization procedures were used, invasive management should be considered in those patients with uncontrolled symptoms despite OMT or high-risk features related to left ventricular function, coronary anatomy, or functional assessment, taking into account the patient expectations and preferences