Obesity and overweight are health problems of multifactorial etiology, which may include changes in the microbiome. In Mexico, more than 30 % of the child population between 5 and 11 years of age ...suffer from being overweight or are obese, which makes it a public health issue in progress. The purpose of this work was to measure the short-chain fatty acid concentration by high-performance liquid chromatography (HPLC), and to characterize the bacterial diversity by ion torrent semiconductor sequencing, of 16S rDNA libraries prepared from stools collected from a sample of well-characterized Mexican children for normal weight, overweight, and obese conditions by anthropometric and biochemical criteria. We found that triglyceride levels are increased in overweight and obese children, who presented altered propionic and butyric acid concentrations in feces. In addition, although the colon microbiota did not show a clear bacterial dysbiosis among the three conditions, the abundance of some particular bacteria was changed with respect to normal controls. We conclude from our results that the imbalance in the abundance of at least nine different bacteria as well as altered short-chain fatty acid concentration in feces is associated to the overweight and obese conditions of Mexican children.
Non-equilibrium molecular dynamics simulations are used to probe the driving forces behind the formation of highly ordered, epitaxially connected superlattices of polyhedral-shaped nanoparticles ...(NPs) at fluid–fluid interfaces. By explicitly modeling coarse-grained ligands that cap the NP surface, it is shown that differences in NP shapes and time-dependent facet-specific ligand densities give rise to drastically different transformation mechanisms. Our results indicate that the extent of screening of the inter-particle interactions by the surrounding solvation environment has a significant impact on reversibility and ultimately the coherence of the final two-dimensional superlattice obtained. For the particle shapes examined, a hexagonal pre-assembly and a square superlattice final assembly (upon preferential ligand desorption from {100} facets) were prevalent; however, cuboctahedral NPs formed intermediate epitaxially bonded branched clusters, which eventually grew and rearranged into a square lattice; in contrast, truncated octahedral NPs exhibited an abrupt rhombic-to-square transition driven by the clustering of their numerous {111}-ligands that favored the stacking of linear NP rods. To track the incipient order in the system, we also outline a set of novel order parameters that measure the local orientation alignment between nearest-neighbor pairs. The simulation protocols advanced in this work could pave the way forward for exploration of the vast phase space associated with the interfacial self-assembly of NPs.
Zebrafish (Danio rerio) have an innate tendency to join shoals. Based on this, we refined visual choice tests to focus on social interaction and novelty preference. Our design follows mouse ...three‐chamber sociability protocols, except testing is conducted under 940 Lux fluorescent lighting. Initially, we compared performance among zebrafish strains: inbred (AB) or wild‐crossbred (WIK) from Zebrafish International Resource Center, to golden and short‐fin from Petco stores. AB fish exhibited a preference for shoaling; they dwelled longest near transparent boxes containing zebrafish, while short fin favored blue boxes without fish. AB and golden exhibited a strong preference for social novelty, not evident in short‐fin or WIK fish. Serotonin and cannabinoids shape mammalian social behavior, and equivalents of both receptor types are expressed in the zebrafish brain. We examined the effects of the cannabinoid receptor agonist WIN 55,212‐2 (1 mg/l), or serotonin 5‐HT1A receptor agonist buspirone (10 mg/l) on Petco short‐fin social choice. Fish were bath exposed to test compounds for 10 min, under these conditions 3HCP55,940 (4 nm) bound to brain with a concentration of 1.9–6.4 fmol/mg 5–30 min afterward. Social approach was measured 20 min after acclimation to the test arena. WIN 55,212‐2 and buspirone increased dwelling near boxed zebrafish. In zebrafish whole‐brain homogenates, buspirone displaced 3H 8‐hydroxy‐N,N‐dipropylaminotetralin (dissociation constant, KD = 16 ± 1.2 nm) with an inhibition constant (Ki) of 1.8 ± 1.0 nm lower than that of WAY 100,635 (Ki∼1000 nm). These fish social choice tests may enhance social behavior research, and are useful for studying the effects of genetic manipulations, pharmaceuticals or environmental toxins.
This study outlines the development of an implicit-solvent model that reproduces the behavior of colloidal nanoparticles at a fluid–fluid interface. The center point of this formulation is the ...generalized quaternion-based orientational constraint (QOCO) method. The model captures three major energetic characteristics that define the nanoparticle configurationposition (orthogonal to the interfacial plane), orientation, and inter-nanoparticle interaction. The framework encodes physically relevant parameters that provide an intuitive means to simulate a broad spectrum of interfacial conditions. Results show that for a wide range of shapes, our model is able to replicate the behavior of an isolated nanoparticle at an explicit fluid–fluid interface, both qualitatively and often nearly quantitatively. Furthermore, the family of truncated cubes is used as a test bed to analyze the effect of changes in the degree of truncation on the potential-of-mean-force landscape. Finally, our results for the self-assembly of an array of cuboctahedra provide corroboration to the experimentally observed honeycomb and square lattices.
The simulation of homogeneous liquid to vapor nucleation is investigated using three rare-event algorithms, boxed molecular dynamics, hybrid umbrella sampling Monte Carlo, and forward flux sampling. ...Using novel implementations of these methods for efficient use in the isothermal-isobaric ensemble, the free energy barrier to nucleation and the kinetic rate are obtained for a Lennard-Jones fluid at stretched and at superheated conditions. From the free energy surface mapped as a function of two order parameters, the global density and largest bubble volume, we find that the free energy barrier height is larger when projected over bubble volume. Using a regression analysis of forward flux sampling results, we show that bubble volume is a more ideal reaction coordinate than global density to quantify the progression of the metastable liquid toward the stable vapor phase and the intervening free energy barrier. Contrary to the assumptions of theoretical approaches, we find that the bubble takes on cohesive non-spherical shapes with irregular and (sometimes highly) undulating surfaces. Overall, the resulting free energy barriers and rates agree well between the methods, providing a set of complementary algorithms useful for studies of different types of nucleation events.
Cubic bicontinuous phases like the double gyroid (G), double diamond (D), and plumber’s nightmare (P) are of great practical interest for many emerging applications requiring highly regular nanoscale ...networks or porous materials. Such phases can be formed from A–B diblock copolymers by the addition of A-type homopolymer over a range of compositions and relative chain lengths. Particle-based molecular simulations were used to delineate the phase diagram in a region where self-consistent field theory predicts the presence of a G–D–P triple point. Since the simulation box size must be commensurate with the morphology-specific 3D unit cell size (which is not known a priori), accurate free energy estimates are required for a range of box sizes, particularly when multiple competing phases can occur at the conditions of interest. A variant of thermodynamic integration was implemented to obtain such free energies (and hence identify the stable phases and their optimal box sizes) by tracing a reversible path connecting the ordered and disordered phases. This method overcomes key limitations of free energy methods based on the evaluation of chemical potentials via molecular insertions. For the range of conditions simulated, evidence was found of D–G, D–P, and G–D–P phase coexistence, consistent with previous theoretical predictions. Our simulations also reveal key differences and similarities in the size and microstructure of the nodes and struts that make up the different types of bicontinuous networks.
The tensile response to uniaxial deformation of polyethylene-based (Tetra-PE) and poly(ethylene oxide)-based (Tetra-PEO) networks of various strand lengths with idealized diamond connectivity have ...been studied via atomistic molecular dynamics simulations. Tetra-PE and Tetra-PEO diamond networks with the same strand length show comparable maximum extensibility but the Young’s moduli and tensile strength of the former are significantly lower than those of the latter, consistent with stronger intersegmental attractions in the amorphous Tetra-PEO networks. The stress–strain curves show that the stress in short-stranded networks increased rapidly and monotonically with strain while for long-stranded networks it increased very little at small strain and then very sharply as the limit of extensibility was approached. The soft response observed at small strains and the strain-induced crystallization that ensues at large strains rendered the deformations largely nonelastic (irreversible). Spontaneous partial crystallization of a long-stranded Tetra-PE diamond network under supercooling was demonstrated, and the resulting system was used to (1) estimate its melting point as the temperature where any crystalline material disappeared abruptly and (2) show that the presence of crystalline material in the undeformed state leads to higher stress responses upon deformation compared to amorphous samples, a result consistent with experimental observations. The spontaneous crystallization of Tetra-PEO networks at large supercooling was unsuccessful due to the slow motions of the network beads and the prohibitively long crystal nucleation times entailed.
We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients.
Five electronic databases and two preprint ...webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology.
Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81-0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44-1.02, p = 0.08; very low QoE) vs. control (standard of care SOC or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71-0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts.
In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.
In this work, a joint experimental and computational study on the synthesis, self‐assembly, and ionic conduction characteristics of a new conjugated liquid crystal quaterthiophene/poly(ethylene ...oxide) (PEO4) consisting of terminal tetraethyleneglycol monomethyl ether groups on both ends of a quaterthiophene core is performed. In agreement with molecular dynamic simulations, temperature‐dependent grazing‐incidence wide angle X‐ray scattering and X‐ray diffraction indicate that the molecule spontaneously forms a smectic phase at ambient temperature as characterized both in bulk and thin film configurations. Significantly, this smectic phase is maintained upon blending with bis(trifluoro‐methanesulfonyl)imide as ion source at a concentration ratio up to r = Li+/EO = 0.05. Nanosegregation between oligothiophene and PEO moieties and π–π stacking of thiophene rings lead to the formation of efficient 2D pathways for ion transport, resulting in thin‐film in‐plane ionic conductivity as high as 5.2 × 10−4 S cm−1 at 70 °C and r = 0.05 as measured by electrochemical impedance spectroscopy. Upon heating the samples above a transition temperature around 95 °C, an isotropic phase forms associated with a pronounced drop in ionic conductivity. Upon cooling, partial and local reordering of the conducting smectic domains leads to an ionic conductivity decrease compared to the as‐cast state.
A new liquid crystal 4T/poly(ethylene oxide) (PEO4) consisting of a quaterthiophene core and PEO segments is synthesized and studied for its self‐assembly behavior both experimentally and theoretically. The 2D in‐plane ionic conductivity provided by nanosegregation between oligothiophene and PEO moieties and π–π stacking of thiophene rings is measured by electrochemical impedance spectroscopy as a function of temperature.
Materials comprising porous structures, often in the form of interconnected concave cavities, are typically assembled from convex molecular building blocks. The use of nanoparticles with a ...characteristic nonconvex shape provides a promising strategy to create new porous materials, an approach that has been recently used with cagelike molecules to form remarkable liquids with “scrabbled” porous cavities. Nonconvex mesogenic building blocks can be engineered to form unique self-assembled open structures with tunable porosity and long-range order that is intermediate between that of isotropic liquids and of crystalline solids. Here we propose the design of highly open liquid-crystalline structures from rigid nanorings with ellipsoidal and polygonal geometry. By exploiting the entropic ordering characteristics of athermal colloidal particles, we demonstrate that high-symmetry nonconvex rings with large internal cavities interlock within a 2D layered structure leading to the formation of distinctive liquid-crystalline smectic phases. We show that these smectic phases possess uniquely high free volumes of up to ∼95%, a value significantly larger than the 50% that is typically achievable with smectic phases formed by more conventional convex rod- or disklike mesogenic particles.
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