Modulatory role of mTOR in trophoblast adaptive response in the early stage of placentation in sheep.

In brief: Fibroblast growth factor-2 (FGF2) is essential for early placenta development in sheep. This study shows that the mechanistic target of rapamycin is the key modulator of trophoblast adaptive response under FGF2 modulation. Abstract: During the early stage of placentation in sheep, normal conceptus development is affected by trophoblast cell functionality, whose dysregulation results in early pregnancy loss. Trophoblast metabolism is supported mainly by histotrophic factors, including fibroblast growth factor-2 (FGF2), which are involved in cell differentiation and function through the modulation of specific cellular mechanisms. The mechanistic target of rapamycin (mTOR) is known as a cellular 'nutrient sensor', but its downstream regulation remains poorly understood. The hypothesis was that during trophoblast development, the FGF2 effect is mediated by mTOR signalling pathway modulation. Primary trophoblast cells from 21-day-old sheep placenta were characterised and subjected to FGF2 and rapamycin treatment to study the effects on cell functionality and gene and protein expression profiles. The model showed mainly mononuclear cells with epithelial cell-like growth and placental morphological properties, expressing typical trophoblast markers. FGF2 promoted cell proliferation and migration under normal culture conditions, whereas mTOR inhibition reversed this effect. When the mTOR signalling pathway was activated, FGF2 failed to influence invasion activity. mTOR inhibition significantly reduced cell motility, but FGF2 supplementation restored motility even when mTOR was inhibited. Interestingly, mTOR inhibition influenced endocrine trophoblast marker regulation. Although FGF2 supplementation did not affect ovine placenta lactogen expression, as observed in the control, interferon-tau was drastically reduced. This study provides new insights into the mechanism underlying mTOR inhibitory effects on trophoblast cell functionality. In addition, as mTOR is involved in the expression of hormonal trophoblast markers, it may play a crucial role in early placenta growth and fetal-maternal crosstalk.

Kawasaki disease and cardiac involvement: an update on the state of the art.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. It has a self-limiting course and so far, represents the most common cause of coronary heart disease acquired in children aged between 6 months and 5 years. The inflammatory process can involve the coronary arteries with the formation of aneurysms and thrombotic occlusions with the risk of sudden death, especially in infants. Myocardial inflammation and abnormalities of cardiac contractility can occur acutely or many years after the disease onset. Therapy must be started within 10 days after the onset of symptoms to reduce the risk of heart complications. Immunoglobulin and aspirin treatment are effective in reducing heart complications. Recent studies have shown new therapeutic strategies (corticosteroids, immunosuppressive and biological drugs) in case of ineffectiveness of treatment with immunoglobulins.

Cationic liposomes formulated with DMPC and a gemini surfactant traverse the cell membrane without causing a significant bio-damage.

Cationic liposomes have been intensively studied both in basic and applied research because of their promising potential as non-viral molecular vehicles. This work was aimed to gain more information on the interactions between the plasmamembrane and liposomes formed by a natural phospholipid and a cationic surfactant of the gemini family. The present work was conducted with the synergistic use of diverse experimental approaches: electro-rotation measurements, atomic force microscopy, ζ-potential measurements, laser scanning confocal microscopy and biomolecular/cellular techniques. Electro-rotation measurements pointed out that the interaction of cationic liposomes with the cell membrane alters significantly its dielectric and geometric parameters. This alteration, being accompanied by significant changes of the membrane surface roughness as measured by atomic force microscopy, suggests that the interaction with the liposomes causes locally substantial modifications to the structure and morphology of the cell membrane. However, the results of electrophoretic mobility (ζ-potential) experiments show that upon the interaction the electric charge exposed on the cell surface does not vary significantly, pointing out that the simple adhesion on the cell surface of the cationic liposomes or their fusion with the membrane is to be ruled out. As a matter of fact, confocal microscopy images directly demonstrated the penetration of the liposomes inside the cell and their diffusion within the cytoplasm. Electro-rotation experiments performed in the presence of endocytosis inhibitors suggest that the internalization is mediated by, at least, one specific pathway. Noteworthy, the liposome uptake by the cell does not cause a significant biological damage.

Clarifying the role of Ru in methanol oxidation at Ru(core)@Pt(shell) nanoparticles.

The catalytic activity of Rucore@Ptshell nanoparticles (NPs) towards CO oxidation, a strongly adsorbed intermediate that compromises the performance of direct methanol fuel cells, is known to be significantly better than at Pt alone. However, a systematic study aimed at understanding the beneficial effect of Ru on Pt during the methanol oxidation reaction (MOR) has not been carried out as yet. Here, Rucore@Ptshell NPs, having a controlled Ptshell coverage of zero to two monolayers and two different Rucore sizes (2 and 3 nm), were synthesized using the simple polyol method to determine the precise role and impact of Ru on the MOR in 0.5 M H2SO4 + 1 M methanol at RT and 60 °C. Because the structure of our Rucore@Ptshell NPs is known with such certainty, we were able to show here that the rate of methanol adsorption/dehydrogenation can be accelerated either by compression of the Ptshell (by making the Rucore larger) when it is less than one monolayer in thickness, or by decreasing the electronic effect of the Rucore on the Ptshell (achieved by adding a second Pt layer to the Ptshell). At low overpotentials, decreasing the Ptshell thickness also helps in increasing the rate of the MOR by enhancing the rate of oxidation of adsorbed CO. Finally, it is shown that the bi-functional effect of Ru on the Ptshell plays only a minor role in the catalysis of the MOR, especially at large particles where CO surface diffusion is facilitated.

Gold nanoparticle array formation on dimpled Ta templates using pulsed laser-induced thin film dewetting.

Here we show that pulsed laser-induced dewetting (PLiD) of a thin Au metallic film on a nano-scale ordered dimpled tantalum (DT) surface results in the formation of a high quality Au nanoparticle (NP) array. In contrast to thermal dewetting, PLiD does not result in deformation of the substrate, even when the Au film is heated to above its melting point. PLiD causes local heating of only the metal film and thus thermal oxidation of the Ta substrate can be avoided, also because of the high vacuum (low pO2) environment employed. Therefore, this technique can potentially be used to fabricate NP arrays composed of high melting point metals, such as Pt, not previously possible using conventional thermal annealing methods. We also show that the Au NPs formed by PLiD are more spherical in shape than those formed by thermal dewetting, likely demonstrating a different dewetting mechanism in the two cases. As the metallic NPs formed on DT templates are electrochemically addressable, a longer-term objective of this work is to determine the effect of NP size and shape (formed by laser vs. thermal dewetting) on their electrocatalytic properties.

Transition from nonresonant to resonant random lasers by the geometrical confinement of disorder.

We report on a transition in random lasers that is induced by the geometrical confinement of the emitting material. Different dye doped paper devices with controlled geometry are fabricated by soft lithography and show two distinguished behaviors in the stimulated emission: in the absence of boundary constraints, the energy threshold decreases for larger laser volumes showing the typical trend of diffusive nonresonant random lasers, while when the same material is lithographed into channels, the walls act as cavity and the resonant behavior typical of standard lasers is observed. The experimental results are consistent with the general theories of random and standard lasers and a clear phase diagram of the transition is reported.

The Multidisciplinary Approach for the Diagnosis of Laryngohyoid Lesions: a Systematic Literature Review and Meta-Analysis.

Background: The diagnosis of neck lesions remains a medico-legal diagnostic challenge because of the complexity of the anatomical relationship of the neck's organs and their anthropometric morphological variability. We compared the multidisciplinary approach using autopsy and postmortem computed tomography (PMCT), postmortem fine preparation (PMFP), postmortem micro-computed tomography (micro-CT), and postmortem magnetic resonance (PMMR) with the performance of a single diagnostic method among them evaluating the significance of different results. The multidisciplinary approach significantly reduced the number of unidentified neck lesions. The analysis demonstrates the need to better define the scan protocols and compose forensic guidelines for radiological application. The results of this study point out the need to compare the different diagnostic approaches in deceased subjects to better define the radiological scan protocol based on a multidisciplinary approach, including autopsy and radiological methods and the radiological scan protocols. Methods: We performed a systematic electronic search of retrospective scientific articles in PubMed, the Scopus database, and the Cochrane Library. The following combinations of words were used: "hyoid fracture"; "comparison between PMCT AND autopsy"; "hyoid fracture PMCT AND autopsy"; "hyoid bone fracture AND forensic imaging"; "hyoid fracture AND PMCT"; "neck fracture PMCT AND autopsy"; "laryngohyoid lesions"; "postmortem CT AND autopsy in strangulation"; "postmortem AND strangulation Signs "; "strangulation virtopsy"; and "strangulation AND MRI". We selected 16 articles that were published between March 2003 and June 2020. We conducted a meta-analysis with R software to evaluate the rates. We obtained related confidence intervals and a forest plot. Results: Thyroid cartilage damages were significantly more common than hyoid bone fractures (61.7% vs 42.2%) in a sample of 128 subjects. The synergic uses of autopsy/PMCT, autopsy/PMFP, autopsy/microCT, and autopsy/PMMR revealed significantly higher rates than a single investigation. We analyzed the PMCT scan data. The scan parameters evaluated were as follows: row, scan sample, reconstruction, kernel, slice thickness, kVp, and mAs. A lack of uniformity in the application of the protocol was observed. Conclusion: Further studies are needed to better define the radiological scan protocols and to draw guidelines to identify the appropriate radiological methods in relation to the specific case.

Hydrophobic nanoporous carbon scaffolds reveal the origin of polarity-dependent electrocapillary imbibition.

An engineered nanoporous carbon scaffold (NCS) consisting of a 3-D interconnected 85 nm nanopore network was used here as a model material to investigate the nanoscale transport of liquids as a function of the polarity and magnitude of an applied potential ('electro-imbibition'), all in 1 M KCl solution. A camera was used to track both meniscus formation and meniscus jump, front motion dynamics, and droplet expulsion, while also quantifying the electrocapillary imbibition height (H) as a function of the applied potential of the NCS material. Although no imbibition was seen over a wide range of potentials, at positive potentials (+1.2 V vs. the potential of zero charge (pzc)), imbibition was correlated with carbon surface electro-oxidation, as confirmed by both electrochemistry and post-imbibition surface analysis, with gas evolution (O2, CO2) seen visually only after imbibition was well underway. At negative potentials, vigorous hydrogen evolution reaction was observed at the NCS/KCl solution interface, well before imbibition began at -0.5 Vpzc, proposed to be nucleated by an electrical double layer charging-driven meniscus jump, followed by processes such as Marangoni flow, adsorption induced deformation, and hydrogen pressure driven flow. This study improves the understanding of electrocapillary imbibition at the nanoscale, being highly relevant in a wide range of multidisciplinary practical applications, including in energy storage and conversion devices, energy-efficient desalination, and electrical-integrated nanofluidics design.

The impact of fabrication conditions on the quality of Au nanoparticle arrays on dimpled Ta templates.

Highly ordered dimpled Ta (DT) nanotemplates, prepared by electrochemical anodization of Ta, were recently reported to be ideally suited for the fabrication of a Au nanoparticle (NP) array using a Au thin film dewetting method. Here, we provide guidance and understanding of the effect of the DT fabrication and Au film deposition steps on the characteristics of the resulting NP array. Specifically, the optimum anodization time, voltage and solution composition are established, and the thickness of the sputter-deposited metal film is shown to be a very important parameter in achieving the desired single Au NP per dimple. The resulting high quality Au NP arrays are demonstrated to be electrochemically addressable, with the total Au surface area, measured electrochemically for large-scale samples, agreeing with the calculated area, based on scanning electron microscope determination of average particle shape and distribution. As the NP formation process proceeds via confined thin film dewetting, the protocol developed here should be applicable to the formation of NP arrays of a range of other metals and alloys.

Deciphering the Interaction of Single-Phase La0.3Sr0.7Fe0.7Cr0.3O3-δ with CO2/CO Environments for Application in Reversible Solid Oxide Cells.

A detailed study aimed at understanding and confirming the reported highly promising performance of a La0.3Sr0.7Fe0.7Cr0.3O3-δ (LSFCr) perovskite catalyst in CO2/CO mixtures, for use in reversible solid oxide fuel cells (RSOFCs), is reported in this work, with an emphasis on chemical and performance stability. This work includes an X-ray diffraction (XRD), thermogravimetric analysis (TGA), and electrochemical study in a range of pO2 atmospheres (pure CO2, CO alone (balance N2), and a 90-70% CO2/10-30% CO containing mixture), related to the different conditions that could be encountered during CO2 reduction at the cathode. Powdered LSFCr remains structurally stable in 20-100% CO2 (balance N2, pO2 = 10-11-10-12 atm) without any decomposition. However, in 30% CO (balance N2, pO2 ∼ 10-26 atm), a Ruddlesden-Popper phase, Fe nanoparticles, and potentially some coke are observed to form at 800 °C. However, this can be reversed and the original perovskite can be recovered by heat treatment in air at 800 °C. While no evidence for coke formation is obtained in 90-70% CO2/10-30% CO (pO2 = 10-17-10-18 atm) mixtures at 800 °C, in 70 CO2/30 CO, minor impurities of SrCO3 and Fe nanoparticles were observed, with the latter potentially beneficial to the electrochemical activity of the perovskite. Consistent with prior work, symmetrical two-electrode full cells (LSFCr used at both electrodes), fed with the various CO2/CO gas mixtures at one electrode and air at the other, showed excellent electrochemical performance at 800 °C, both in the SOFC and in SOEC modes. Also, LSFCr exhibits excellent stability during CO2 electrolysis in medium-term potentiostatic tests in all gas mixtures, indicative of its excellent promise as an electrode material for use in symmetrical solid oxide cells.

Droplet Lasers for Smart Photonic Labels.

Microscopic lasers represent a promising tool for the development of cutting-edge photonic devices thanks to their ability to enhance light-matter interaction at the microscale. In this work, we realize liquid microlasers with tunable emission by exploiting the self-formation of three-dimensional liquid droplets into a polymeric matrix driven by viscoelastic dewetting. We design a flexible device to be used as a smart photonic label which is detachable and reusable on various types of substrates such as paper or fabric. The innovative lasing emission mechanism proposed here is based on whispering gallery mode emission coupled to random lasing, the latter prompted by the inclusion of dielectric compounds into the active gain medium. The wide possibility of modulating the emission wavelength of the microlasers by acting on different parameters, such as the cavity size, type and volume fraction of the dielectrics, and gain medium, offers a multitude of spectroscopic encoding schemes for the realization of photonic barcodes and labels to be employed in anticounterfeiting applications and multiplexed bioassays.

Wetting dynamics of nanoliter water droplets in nanoporous media.

HYPOTHESIS: The Lucas-Washburn (L-W) equation is the classical theory to describe the dynamics of spontaneous imbibition in single micro-channels and micro-scale porous media. However, for nanoliter droplets imbibition in nanoporous media, the L-W equation may not be suitable, due to the nanoscale liquid-solid interactions, e.g., contact line pinning and capillary condensation. In addition, for an intrinsically hydrophobic nanoporous substrate, spontaneous imbibition of a nanoliter droplet is hypothesized to occur if capillary condensation had occurred internally already. EXPERIMENTS: A nanoporous carbon scaffold was synthesized and used as a model nanoporous medium. A recently-developed micro-injection technique was used to generate a series of nanoliter water droplets (2.8-34 nL); the entire wetting dynamics (i.e., apparent contact angle and droplet volume as a function of time) were observed inside an environmental scanning electron microscope. FINDINGS: The L-W equation does not describe the wetting dynamics of nanoliter water droplets in nanoporous media. A new theoretical model is developed to characterize the corresponding dynamics. It is demonstrated that, even for an intrinsically hydrophobic nanoporous substrate, spontaneous imbibition of a nanoliter droplet can occur if capillary condensation had occurred internally already.

Controlled interconversion of nanoarray of ta dimples and high aspect ratio ta oxide nanotubes.

We report the controlled formation of either high-aspect-ratio Ta(2)O(5) nanotubes or an organized nanoarray of Ta dimples by Ta anodization in a single H(2)SO(4) + HF solution. Dimpled Ta is the stable surface morphology in the first few seconds, followed by the growth of dense and fully vertically aligned Ta(2)O(5) nanotubes (up to 2.5 microm long). After 2 min, the dimpled surface morphology reappears, related to the build-up of a resistive Ta fluoride surface layer.

The dispersion of spherical droplets in source-sink flows and their relevance to the COVID-19 pandemic.

In this paper, we investigate the dynamics of spherical droplets in the presence of a source-sink pair flow field. The dynamics of the droplets is governed by the Maxey-Riley equation with the Basset-Boussinesq history term neglected. We find that, in the absence of gravity, there are two distinct behaviors for the droplets: small droplets cannot go further than a specific distance, which we determine analytically, from the source before getting pulled into the sink. Larger droplets can travel further from the source before getting pulled into the sink by virtue of their larger inertia, and their maximum traveled distance is determined analytically. We investigate the effects of gravity, and we find that there are three distinct droplet behaviors categorized by their relative sizes: small, intermediate-sized, and large. Counterintuitively, we find that the droplets with a minimum horizontal range are neither small nor large, but of intermediate size. Furthermore, we show that in conditions of regular human respiration, these intermediate-sized droplets range in size from a few µm to a few hundred µm. The result that such droplets have a very short range could have important implications for the interpretation of existing data on droplet dispersion.

Ultrasensitive and Label-Free Detection of the Measles Virus Using an N-Heterocyclic Carbene-Based Electrochemical Biosensor.

With the current intense need for rapid and accurate detection of viruses due to COVID-19, we report on a platform technology that is well suited for this purpose, using intact measles virus for a demonstration. Cases of infection due to the measles virus are rapidly increasing, yet current diagnostic tools used to monitor for the virus rely on slow (>1 h) technologies. Here, we demonstrate the first biosensor capable of detecting the measles virus in minutes with no preprocessing steps. The key sensing element is an electrode coated with a self-assembled monolayer containing the measles antibody, immobilized through an N-heterocyclic carbene (NHC). The intact virus is detected by changes in resistance, giving a linear response to 10-100 µg/mL of the intact measles virus without the need to label or process the sample. The limit of detection is 6 µg/mL, which is at the lower limit of concentrations that can cause infections in primates. The NHC-based biosensors are shown to be superior to thiol-based systems, producing an approximately 10× larger response and significantly greater stability toward repeated measurements and long-term storage. This NHC-based biosensor thus represents an important development for both the rapid detection of the measles virus and as a platform technology for the detection of other biological targets of interest.

Cuttlefish: Color Mapping for Dynamic Multi-Scale Visualizations.

Visualizations of hierarchical data can often be explored interactively. For example, in geographic visualization, there are continents, which can be subdivided into countries, states, counties and cities. Similarly, in models of viruses or bacteria at the highest level are the compartments, and below that are macromolecules, secondary structures (such as α-helices), amino-acids, and on the finest level atoms. Distinguishing between items can be assisted through the use of color at all levels. However, currently, there are no hierarchical and adaptive color mapping techniques for very large multi-scale visualizations that can be explored interactively. We present a novel, multi-scale, color-mapping technique for adaptively adjusting the color scheme to the current view and scale. Color is treated as a resource and is smoothly redistributed. The distribution adjusts to the scale of the currently observed detail and maximizes the color range utilization given current viewing requirements. Thus, we ensure that the user is able to distinguish items on any level, even if the color is not constant for a particular feature. The coloring technique is demonstrated for a political map and a mesoscale structural model of HIV. The technique has been tested by users with expertise in structural biology and was overall well received.

Enhanced Signal Amplification in a Toll-like Receptor-4 Biosensor Utilizing Ferrocene-Terminated Mixed Monolayers.

A major challenge in effectively treating infections is to provide timely diagnosis of a bacterial or viral agent. Current cell culture methods require >24 h to identify the cause of infection. The Toll-like Receptor (TLR) family of proteins can identify classes of pathogens and has been shown to work well in an impedance-based biosensor, where the protein is attached to an electrode via a self-assembled monolayer (SAM). While the sensitivity of these sensors has been good, they contain a high resistance (>1 kΩ) SAM, generating relatively small signals and requiring longer data collection, which is ill-suited to implementation outside of a laboratory. Here, we describe a novel approach to increase the signal magnitude and decrease the measurement time of a TLR-4 biosensor by inserting a redox-active ferrocenyl-terminated alkanethiol into a mixed SAM containing hydroxyl- and carboxyl-terminated alkanethiols. The SAM formation and modification was confirmed via contact angle and X-ray photoelectron spectroscopy measurements, with TLR-4 immobilization demonstrated through a modified immunosorbent assay. It is shown that these TLR-4 biosensors respond selectively to their intended target, Gram-negative bacteria at levels between 1 and 105 lysed cells/mL, while remaining insensitive to Gram-positive bacteria or viral particles at up to 105 particles/mL. Furthermore, the signal enhancement due to the addition of ferrocene decreased the measurement time to less than 1 min and has enabled this sensor to be used with an inexpensive, portable, hand-held potentiostat that could be easily implemented in field settings.

Nanoengineered Ircore@Ptshell Nanoparticles with Controlled Pt Shell Coverages for Direct Methanol Electro-Oxidation.

The design and application of bimetallic alloy nanoparticles (NPs) for electrocatalytic applications are challenged by the need to clearly identify and understand the individual effect of each component. In the present work, the focus has been on PtIr NPs, with alloyed NPs being previously shown to be active toward the methanol oxidation reaction (MOR), but for which the mode of action of the Ir component remains uncertain. We have therefore nanoengineered a family of Ircore@Ptshell NPs, using a modified polyol method, to control the Pt shell coverage (up to 2 monolayers) and thus to allow the separation of the bifunctional and electronic effects of Ir on the Pt activity. It is shown that the Ir core size and crystallinity do not change with the deposition of the Pt shell, as confirmed by transmission electron microscopy and X-ray diffraction. CO stripping and hydrogen underpotential deposition/removal were used for the first time to determine the surface composition of the Ircore@Ptshell NPs. It is shown that the Ircore enhances the MOR activity of the Ptshell primarily through the bifunctional effect, with an optimum Pt coverage of 0.4 of a monolayer. At 60 °C, an additional electronic effect of Ir on Pt can be discerned, causing an inhibition in the MOR rate by weakening the adsorption of methanol on the Ptshell, thus helping to remove the adsorbed CO intermediate from the shell surface.