Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model.

Introduction: Angiotensin receptor-neprilysin inhibitor (ARNi), comprised of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has established itself as a safe and effective intervention for hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension. Methods: Dahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were employed in this study to investigate the anti-hypertensive efficacy of S086 and compare it with the first ARNi-LCZ696. Results and discussion: The study showed that oral administration of S086 dose-dependently lowered blood pressure (P < 0.001). The middle dosage of S086 (23 mg/kg) exhibited efficacy comparable to LCZ696 (68 mg/kg), while also demonstrating superiority at specific time points (P < 0.05). Notably, water consumption slightly decreased post-treatment compared to the vehicle group. Furthermore, there were significant increases in natriuresis and diuresis observed on the first day of treatment with 23 mg/kg and 68 mg/kg S086 (P < 0.001). However, over the course of treatment, the effects in all treatment groups gradually diminished. This study demonstrates the anti-hypertensive efficacy of S086 in DSS hypertensive rat model, offering promising avenues for the clinical development of S086 as a hypertension treatment.

Pharmacodynamic and pharmacokinetic effects of S086, a novel angiotensin receptor neprilysin inhibitor.

BACKGROUND AND PURPOSE: Angiotensin receptor-NEP inhibitor (ARNi), which includes an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has been proven safe and effective for treating heart failure with reduced ejection fraction (HF-REF). S086 is a novel single-molecule ARNi that includes the molecular moieties of EXP3174 (the active metabolite of the ARB losartan) and sacubitril (a NEP inhibitor prodrug) in a 1:1 M ratio. We performed preclinical animal model studies to evaluate the efficacy of S086 in treating HF. EXPERIMENTAL APPROACH: Rat and dog models of myocardial ischemia-induced chronic heart failure were used in this research. PRINCIPAL RESULTS: The oral administration of S086 dose-dependently lowered the heart weight index, attenuated cardiac fibrosis, and improved left ventricular ejection fraction, shortening fraction, and cardiac output, without effects on hemodynamics in animal models of myocardial ischemia-induced chronic heart failure. A comparable protective effect to LCZ696 was observed for S086 at an equal molar dose in dog models. In addition, S086 was superior to LCZ696 since it significantly reversed the decrease in left ventricular posterior wall end-systolic thickness. CONCLUSION: This animal study suggests that S086 is effective in treating myocardial ischemia-induced chronic heart failure.

Laser-induced nanoscale thermocapillary flow for purification of aligned arrays of single-walled carbon nanotubes.

Although aligned arrays of single-walled carbon nanotubes (SWNTs) have outstanding potential for use in broad classes of advanced semiconductor devices, the relatively large population of metallic SWNTs (m-SWNTs) that results from conventional growth techniques leads to significantly degraded performance. Recently reported methods based on thermocapillary effects that enable removal of m-SWNTs from such arrays offer exceptional levels of efficiency, but the procedures are cumbersome and require multiple processing steps. Here we present a simple, robust alternative that yields pristine arrays of purely semiconducting SWNTs (s-SWNTs) by use of irradiation with an infrared laser. Selective absorption by m-SWNTs coated with a thin organic film initiates nanoscale thermocapillary flows that lead to exposure only of the m-SWNTs. Reactive ion etching eliminates the m-SWNTs without damaging the s-SWNTs; removal of the film completes the purification. Systematic experimental studies and computational modeling of the thermal physics illuminates the essential aspects of this process. Demonstrations include use of arrays of s-SWNTs formed in this manner as semiconducting channel materials in statistically relevant numbers of transistors to achieve both high mobilities (>900 cm2 V(-1) s(-1)) and switching ratios (>10(4)). Statistical analysis indicates that the arrays contain at least 99.8% s-SWNTs and likely significantly higher.

Microwave purification of large-area horizontally aligned arrays of single-walled carbon nanotubes.

Recent progress in the field of single-walled carbon nanotubes (SWNTs) significantly enhances the potential for practical use of this remarkable class of material in advanced electronic and sensor devices. One of the most daunting challenges is in creating large-area, perfectly aligned arrays of purely semiconducting SWNTs (s-SWNTs). Here we introduce a simple, scalable, large-area scheme that achieves this goal through microwave irradiation of aligned SWNTs grown on quartz substrates. Microstrip dipole antennas of low work-function metals concentrate the microwaves and selectively couple them into only the metallic SWNTs (m-SWNTs). The result allows for complete removal of all m-SWNTs, as revealed through systematic experimental and computational studies of the process. As one demonstration of the effectiveness, implementing this method on large arrays consisting of ~20,000 SWNTs completely removes all of the m-SWNTs (~7,000) to yield a purity of s-SWNTs that corresponds, quantitatively, to at least to 99.9925% and likely significantly higher.

3D hierarchical architectures based on self-rolled-up silicon nitride membranes.

This study presents the superior structural versatility of strained silicon nitride (SiNx) membranes as a platform for three-dimensional (3D) hierarchical tubular architectures. The effects of compressive and tensile stressed SiNx layer thickness on the self-rolled-up tube curvature, the sacrificial layer etching anisotropy on rolling direction and chirality, and stress engineering by localized thickness control or thermal treatment, are explored systematically. Using strained SiNx membranes as an electrically insulating and optically transparent mechanical support, compact 3D hierarchical architectures involving carbon nanotube arrays and passive electronic components are demonstrated by releasing the functional structures deposited and patterned in 2D. These examples highlight the uniqueness of this platform that exploits 2D processing and self-assembly to achieve highly functional 3D structures.

Using nanoscale thermocapillary flows to create arrays of purely semiconducting single-walled carbon nanotubes.

Among the remarkable variety of semiconducting nanomaterials that have been discovered over the past two decades, single-walled carbon nanotubes remain uniquely well suited for applications in high-performance electronics, sensors and other technologies. The most advanced opportunities demand the ability to form perfectly aligned, horizontal arrays of purely semiconducting, chemically pristine carbon nanotubes. Here, we present strategies that offer this capability. Nanoscale thermocapillary flows in thin-film organic coatings followed by reactive ion etching serve as highly efficient means for selectively removing metallic carbon nanotubes from electronically heterogeneous aligned arrays grown on quartz substrates. The low temperatures and unusual physics associated with this process enable robust, scalable operation, with clear potential for practical use. We carry out detailed experimental and theoretical studies to reveal all of the essential attributes of the underlying thermophysical phenomena. We demonstrate use of the purified arrays in transistors that achieve mobilities exceeding 1,000 cm(2) V(-1) s(-1) and on/off switching ratios of ∼10,000 with current outputs in the milliamp range. Simple logic gates built using such devices represent the first steps toward integration into more complex circuits.

Quantitative thermal imaging of single-walled carbon nanotube devices by scanning Joule expansion microscopy.

Electrical generation of heat in single-walled carbon nanotubes (SWNTs) and subsequent thermal transport into the surroundings can critically affect the design, operation, and reliability of electronic and optoelectronic devices based on these materials. Here we investigate such heat generation and transport characteristics in perfectly aligned, horizontal arrays of SWNTs integrated into transistor structures. We present quantitative assessments of local thermometry at individual SWNTs in these arrays, evaluated using scanning Joule expansion microscopy. Measurements at different applied voltages reveal electronic behaviors, including metallic and semiconducting responses, spatial variations in diameter or chirality, and localized defect sites. Analytical models, validated by measurements performed on different device structures at various conditions, enable accurate, quantitative extraction of temperature distributions at the level of individual SWNTs. Using current equipment, the spatial resolution and temperature precision are as good as ∼100 nm and ∼0.7 K, respectively.

Stretchable, transparent graphene interconnects for arrays of microscale inorganic light emitting diodes on rubber substrates.

This paper describes the fabrication and design principles for using transparent graphene interconnects in stretchable arrays of microscale inorganic light emitting diodes (LEDs) on rubber substrates. We demonstrate several appealing properties of graphene for this purpose, including its ability to spontaneously conform to significant surface topography, in a manner that yields effective contacts even to deep, recessed device regions. Mechanics modeling reveals the fundamental aspects of this process, as well as the use of the same layers of graphene for interconnects designed to accommodate strains of 100% or more, in a completely reversible fashion. These attributes are compatible with conventional thin film processing and can yield high-performance devices in transparent layouts. Graphene interconnects possess attractive features for both existing and emerging applications of LEDs in information display, biomedical systems, and other environments.

Monolithic integration of arrays of single-walled carbon nanotubes and sheets of graphene.

Sheets of graphene and arrays of single-walled carbon nanotubes (SWNTs) are formed separately using chemical vapor deposition techniques onto different optimized growth substrates. Techniques of transfer printing provide a route to integration, yielding two terminal devices and transistors in which patterned structures of graphene form the electrodes and the SWNTs arrays serve as the semiconducting channels.

Layer-by-layer transfer of multiple, large area sheets of graphene grown in multilayer stacks on a single SiC wafer.

Here we report a technique for transferring graphene layers, one by one, from a multilayer deposit formed by epitaxial growth on the Si-terminated face of a 6H-SiC substrate. The procedure uses a bilayer film of palladium/polyimide deposited onto the graphene coated SiC, which is then mechanically peeled away and placed on a target substrate. Orthogonal etching of the palladium and polyimide leaves isolated sheets of graphene with sizes of square centimeters. Repeating these steps transfers additional sheets from the same SiC substrate. Raman spectroscopy, scanning tunneling spectroscopy, low-energy electron diffraction and X-ray photoelectron spectroscopy, together with scanning tunneling, atomic force, optical, and scanning electron microscopy reveal key properties of the materials. The sheet resistances determined from measurements of four point probe devices were found to be ∼2 kΩ/square, close to expectation. Graphene crossbar structures fabricated in stacked configurations demonstrate the versatility of the procedures.