Imaging characterization of myocardial function, fibrosis, and perfusion in a nonhuman primate model with heart failure-like features.

Introduction: The availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model. Methods: The NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF < 65% (termed as HFrEF, n = 10) and LVEF ≥ 65% with diastolic dysfunction (termed as HFpEF, n = 10). Another group of ten healthy monkeys was used as the healthy control. All monkeys underwent a CMR study to measure global longitudinal strain (GLS), myocardial extracellular volume (ECV), and late gadolinium enhancement (LGE). In healthy controls and HFpEF group, quantitative perfusion imaging scans at rest and under dobutamine stress were performed and myocardial perfusion reserve (MPR) was subsequently obtained. Results: No LGE was observed in any monkey. Monkeys with HF-like features were significantly older, compared to the healthy control group. There were significant differences among the three groups in ECV (20.79 ± 3.65% in healthy controls; 27.06 ± 3.37% in HFpEF group, and 31.11 ± 4.50% in HFrEFgroup, p < 0.001), as well as for stress perfusion (2.40 ± 0.34 ml/min/g in healthy controls vs. 1.28 ± 0.24 ml/min/g in HFpEF group, p < 0.01) and corresponding MPR (1.83 ± 0.3 vs. 1.35 ± 0.29, p < 0.01). After adjusting for age, ECV (p = 0.01) and MPR (p = 0.048) still showed significant differences among the three groups. Conclusion: Our preliminary imaging findings demonstrated cardiac dysfunction, elevated ECV, and/or reduced MPR in this HF-like NHP model. This pilot study laid the foundation for further mechanistic research and the development of a drug testing platform for distinct HF pathophysiology.

A robust fiber-based quantum thermometer coupled with nitrogen-vacancy centers.

The nitrogen-vacancy center in diamond has been broadly applied in quantum sensing since it is sensitive to different physical quantities. Meanwhile, it is difficult to isolate disturbances from unwanted physical quantities in practical applications. Here, we present a fiber-based quantum thermometer by tracking the sharp-dip in the zero-field optically detected magnetic resonance spectrum in a high-density nitrogen-vacancy ensemble. Such a scheme can not only significantly isolate the magnetic field and microwave power drift but also improve the temperature sensitivity. Thanks to its simplicity and compatibility in implementation and robustness, this quantum thermometer is then applied to the surface temperature imaging of an electronic chip with a sensitivity of 18mK/Hz. It thus paves the way to high sensitive temperature measurements in ambiguous environments.

Electrochemical preparation and properties of a Mg-Li-Y alloy via co-reduction of Mg(ii) and Y(iii) in chloride melts.

Mg-Li based alloys have been widely used in various fields. However, the widespread use of Mg-Li based alloys were restricted by their poor properties. The addition of rare earth element in Mg-Li can significantly improve the properties of alloys. In the present work, different electrochemical methods were used to investigate the electrochemical behavior of Y(iii) on the W electrode in LiCl-KCl melts and LiCl-KCl-MgCl2 melts. In LiCl-KCl melts, typical cyclic voltammetry was used to study the electrochemical mechanism and thermodynamic parameters for the reduction of Y(iii) to metallic Y. In LiCl-KCl-MgCl2 melts, the formation mechanism of Mg-Y intermetallic compounds was investigated, and the results showed that only one kind of Mg-Y intermetallic compound was formed under our experimental conditions. Mg-Li-Y alloys were prepared via galvanostatic electrolysis, and XRD and SEM equipped with EDS analysis were used to analyze the samples. Because of the restrictions of EDS analysis, ICP-AES was used to analyze the Li content in Mg-Li-Y alloys. The microhardness and Young's modulus of the Mg-Li-Y alloys were then evaluated.

Publisher Correction: Orexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Orexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep.

The relationship between orexin/hypocretin and rapid eye movement (REM) sleep remains elusive. Here, we find that a proportion of orexin neurons project to the sublaterodorsal tegmental nucleus (SLD) and exhibit REM sleep-related activation. In SLD, orexin directly excites orexin receptor-positive neurons (occupying ~3/4 of total-population) and increases gap junction conductance among neurons. Their interaction spreads the orexin-elicited partial-excitation to activate SLD network globally. Besides, the activated SLD network exhibits increased probability of synchronized firings. This synchronized excitation promotes the correspondence between SLD and its downstream target to enhance SLD output. Using optogenetics and fiber-photometry, we consequently find that orexin-enhanced SLD output prolongs REM sleep episodes through consolidating brain state activation/muscle tone inhibition. After chemogenetic silencing of SLD orexin signaling, a ~17% reduction of REM sleep amounts and disruptions of REM sleep muscle atonia are observed. These findings reveal a stabilization role of orexin in REM sleep.

Liver extracellular volume fraction values obtained with magnetic resonance imaging can quantitatively stage liver fibrosis: a validation study in monkeys with nonalcoholic steatohepatitis.

OBJECTIVES: This study was to evaluate the diagnostic value of liver extracellular volume (LECV) for the staging of liver fibrosis in a cynomolgus monkey model of nonalcoholic steatohepatitis (NASH). METHODS: Forty-eight cynomolgus monkeys were enrolled in this prospective study. There are 17 healthy monkeys and 31 monkeys with NASH. Ten of these monkeys were used for repeatability assessment. The remaining 38 monkeys were used to compare LECV with other indicators including pathology fibrosis score, native T1, and serum chemical indexes by Spearman, Pearson correlation test, and ROC curves. The inter-reader variability was assessed by interclass correlation. The repeatability measurement of LECV was analyzed using Bland-Altman plots and the coefficient of variation. Partial correlation analysis was performed to assess the effects of fat content and inflammation scores on the correlation between LECV/T1 and liver fibrosis score. RESULTS: This study demonstrated a good intra-reader agreement (intraclass correlation = 0.79) of LECV in all monkeys and an excellent repeatability in 10 monkeys (coefficient of variation = 2.01%). The LECV has a strong correlation with the fibrosis score (r = 0.949; p < 0.0001), low-density lipoprotein (r = 0.72; p < 0.0001), and cholesterol (r = 0.70; p < 0.0001). LECV showed high diagnostic efficacy in the diagnosis of liver fibrosis (area under the curve of ROC, 0.945~1; p < 0.001). CONCLUSIONS: LECV may serve as a noninvasive valuable biomarker for the quantification and differentiating of the non-severe liver fibrosis (stage ≤ F3). However, circulating serum markers low-density lipoprotein and cholesterol (CHO) may not serve for this purpose. KEY POINTS: • This paper demonstrated the excellent repeatability (intraclass correlation coefficient = 0.79) of LECV in monkey animal model. • LECV-MRI has a strong correlation with histopathological fibrosis score stage (r = 0.949; p < 0.0001) and shows high diagnostic efficacy in the staging of non-severe liver fibrosis (the area under ROC curve ≥ 0.945). • The new fibrosis score maps appeared to provide a better imaging tool for the spatial assessment of liver fibrosis. It may eventually facilitate the diagnosis of liver fibrosis distribution.

Orexin exerts excitatory effects on reticulospinal neurons in the rat gigantocellular reticular nucleus through the activation of postsynaptic orexin-1 and orexin-2 receptors.

Previous studies have revealed that orexin may actively participate in central motor control. The gigantocellular reticular nucleus (Gi) is a key element of the brainstem motor inhibitory system. The descending orexinergic projections also reach Gi region, and microinjection of orexin into Gi causes robust muscle tone inhibition. However, the modulation effects of orexin on Gi neurons remain unclear. In the present study, using whole-cell patch-clamp recordings, we initially observed that orexin elicited an inward current in Gi neurons at a holding potential of -70mV in a concentration-dependent manner. By combining electrophysiology with neuropharmacological methods, we further determined that the orexin-induced inward current was directly mediated by the activation of postsynaptic orexin-1 and orexin-2 receptors. Moreover, orexin did not affect the frequency and amplitude of miniature excitatory and inhibitory postsynaptic currents in Gi neurons, which suggests that orexin had no effects on neurotransmission to these neurons. Therefore, the direct excitatory effect of orexin on an inhibitory motor structure, the Gi, was reported in the present study. This modulation may be integrated into the role of orexin in central motor control.

Anisotropic growth of one-dimensional silver rod-needle and plate-belt heteronanostructures induced by twins and hcp phase.

In this paper, we report a one-step, high-yield synthesis of one-dimensional Ag heteronanostructures in aqueous solution. Besides the usual fcc phase of Ag, the heteronanostructures also contain a rare hcp (4H polytypic) phase, which favors asymmetrical growth. The rod-needle heteronanostructures (RNHSs) and plate-belt heteronanostructures (PBHSs) are formed through two different mechanisms. For RNHSs, the 4H and fcc phases coexist but have different densities in different segments, while for PBHSs, the fcc and 4H crystal structures exist in plate and belt segments, respectively. Condition-sensitive coexisting phase preferences can be applied as a new way of controlling the shape and thus the properties of Ag nanostructures.

Nanospheres of silver nanoparticles: agglomeration, surface morphology control and application as SERS substrates.

This paper reports a high-yield synthesis of Ag nanospheres made up of primary nanoparticles. The size of the silver nanospheres can be controlled by changing the concentration of poly(vinylpyrrolidone) (PVP) which acts as a stabilizer. In addition, the surface morphology of the nanospheres can be well controlled through controlling the shape of primary Ag nanoparticles by introducing a small quantity of ionic capping agents in the solution. Different surface morphologies of Ag nanospheres lead to different surface plasmon resonance (SPR) and surface-enhanced Raman scattering (SERS) properties. The SERS property of the nanospheres used as substrates is very sensitive to the nanoscale characteristics of the surfaces, and the nanospheres with sharp tips on their surface exhibit much better Raman scattering enhancement than non-agglomerated spherical Ag nanoparticles.

Synthesis and characterization of indium oxide nanobubbles with ultrathin single crystal shells.

Nanobubbles with ultrathin single crystal shells, a new kind of closed nanostructure, have been synthesized from a nonlayered indium oxide semiconductor.