Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin-A receptor antagonist.

This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin-A (ETA ) receptor antagonist, in healthy subjects. The primary objectives of this first-in-human phase I study, comprised of single-ascending-dose, multiple-ascending-dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin-1 (ET-1) and total bile acids (TBA). Single doses of 10 to 100 mg and multiple daily doses of 20 and 50 mg for 6 days were well tolerated. SC0062 was rapidly absorbed and plasma exposure of SC0062 and M18 increased disproportionately with dose, achieving steady state by day 3, with accumulation ratios of 1.22 and 1.89 on day 6 for SC0062 and M18, respectively. The geometric mean (geometric standard deviation) terminal elimination half-life (t1/2 ) values of SC0062 and M18 were 7.25 (1.70) h and 13.73 (1.32) h, respectively. Plasma ET-1 concentrations were dose-proportional, whereas plasma TBA concentrations behaved erratically. Following a single 50 mg dose of SC0062 after a high-fat meal, Cmax values for SC0062 and M18 increased by 41% and 32%, respectively, and median Tmax values for SC0062 were 3 h longer than fasting values; exposure was unaffected. These favorable safety, PK, and PD results provide a foundation for further studies of SC0062 in pulmonary arterial hypertension, chronic kidney disease, and other relevant indications.

Regulation of Released Alkali from Gel Polymer Electrolyte in Quasi-Solid State Zn-Air Battery.

Gel polymer electrolyte (GPE) in quasi-solid state Zn-air battery (QSZAB) will release alkali during cycling, resulting in gradual dehydration of GPE, corrosion of Zn electrode, Zn dendrites growth, and therefore inferior performance. Here, hollow Sn microspheres are prepared on Zn substrate by the technique of colloidal self-assembly. The inner surfaces of hollow Sn microspheres are modified by 2-hydroxypropyl-ß-cyclodextrin (hollow Sn-inner HPßCD) to regulate the released alkali at GPE|anode interface. The hollow Sn-inner HPßCD can lessen the leakage of released alkali, make stored alkali diffuse back to GPE during the charging process, and mitigate the loss of soluble Zn(OH)4 2- to suppress Zn dendrites growth. Resultantly, GPE in QSZAB with hollow Sn-inner HPßCD exhibits a high retention capacity for alkaline solution. The cell also exhibits a long cyclic lifespan of 127 h due to the effective regulation of released alkali, which outperforms QSZAB without hollow Sn-inner HPßCD by 7.94 times. This work rivets the regulation of released alkali at GPE|anode interface, providing new insight to improve QSZABs' performance.

Ionic Covalent Organic Frameworks-Derived Cobalt Single Atoms and Nanoparticles for Efficient Oxygen Electrocatalysis.

Metal single atoms show outstanding electrocatalytic activity owing to the abundant atomic reactive sites and superior stability. However, the preparation of single atoms suffers from inexorable metal aggregation which is harmful to electrocatalytic activity. Here, ionic covalent organic frameworks (iCOFs) are employed as the sacrificial precursor to mitigate the metal aggregation and subsequent formation of bulky particles. Molecular dynamics simulation shows that iCOFs can trap and confine more Co ions as compared to neutral COFs, resulting in the formation of a catalyst composed of Co single atoms and uniformly distributed Co nanoparticles (CoSA &CoNP-10 ). However, the neutral COFs derive a catalyst composed of Co atomic clusters and large Co nanoparticles (CoAC &CoNP-25 ). The CoSA &CoNP-10 catalyst exhibits higher oxygen bifunctional electrocatalytic activities than CoAC &CoNP-25 , coinciding with the density functional theory results. Taking the CoSA &CoNP-10 as the air cathode in Zn-air batteries (ZABs), the aqueous ZAB presents a high power density of 181 mW cm-2 , a specific capacity of 811 mAh g-1 as well as a long cycle life of 407 h at a current density of 10 mA cm-2 , while the quasi-solid state ZAB displays a power density of 179 mW cm-2 and the cycle life of 30 h.

Ionic Covalent Organic Frameworks for Energy Devices.

Covalent organic frameworks (COFs) are a class of porous crystalline materials whose facile preparation, functionality, and modularity have led to their becoming powerful platforms for the development of molecular devices in many fields of (bio)engineering, such as energy storage, environmental remediation, drug delivery, and catalysis. In particular, ionic COFs (iCOFs) are highly useful for constructing energy devices, as their ionic functional groups can transport ions efficiently, and the nonlabile and highly ordered all-covalent pore structures of their backbones provide ideal pathways for long-term ionic transport under harsh electrochemical conditions. Here, current research progress on the use of iCOFs for energy devices, specifically lithium-based batteries and fuel cells, is reviewed in terms of iCOF backbone-design strategies, synthetic approaches, properties, engineering techniques, and applications. iCOFs are categorized as anionic COFs or cationic COFs, and how each of these types of iCOFs transport lithium ions, protons, or hydroxides is illustrated. Finally, the current challenges to and future opportunities for the utilization of iCOFs in energy devices are described. This review will therefore serve as a useful reference on state-of-the-art iCOF design and application strategies focusing on energy devices.

Nanofiber Composite for Improved Water Retention and Dendrites Suppression in Flexible Zinc-Air Batteries.

Water loss of the gel polymer electrolytes (GPEs) and dendrites growth on Zn anode are overriding obstacles to applying flexible zinc-air batteries (ZABs) for wearable electronic devices. Nearly all previous efforts aim at developing novel GPEs with enhanced water retention and therefore elongate their lifespan. Herein, a facile interface engineering strategy is proposed to retard the water loss of GPE from the half-open structured air cathode. In detail, the poly(ethylene vinyl acetate)/carbon powder (PEVA-C) nanofiber composite interface layer with features of hydrophobicity, high conductivity, air permeability, and flexibility are prepared on the carbon cloth and set up between the GPE and electrode. The as-assembled ZAB with simple alkaline PVA GPE exhibits an impressive cycle life of 230 h, which outperforms ZAB without the PEVA-C nanofibers interface layer by 14 times. Additionally, the growth of Zn dendrites can be suppressed due to the tardy water loss of GPE.

Multilevel Resistive Switching Memory Based on a CH3NH3PbI 3-xClx Film with Potassium Chloride Additives.

High-quality CH3NH3PbI 3-xClx (MAPIC) films were prepared using potassium chloride (KCl) as an additive on indium tin oxide (ITO)-coated glass substrates using a simple one-step and low-temperature solution reaction. The Au/KCl-MAPIC/ITO/glass devices exhibited obvious multilevel resistive switching behavior, moderate endurance, and good retention performance. Electrical conduction analysis indicated that the resistive switching behavior of the KCl-doped MAPIC films was primarily attributed to the trap-controlled space-charge-limited current conduction that was caused by the iodine vacancies in the films. Moreover, the modulations of the barrier in the Au/KCl-MAPIC interface under bias voltages were thought to be responsible for the resistive switching in the carrier injection trapping/detrapping process.

Phosphorus/nitrogen co-doped and bimetallic MOF-derived cathode for all-solid-state rechargeable zinc-air batteries.

With the merits of high safety and energy density, all-solid-state zinc-air batteries possess potential applications in flexible and wearable electronic devices. Especially, the air cathodes with bifunctional catalytic activity, i.e. oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) have been received enormous attention. In this work, we provide a novel phosphorus/nitrogen co-doped and bimetallic metal-organic framework (MOF)-derived cathode configurated with phosphorus-doped bimetallic FeNi alloys and a nitrogen-doped porous carbon layer loaded on graphene (P-FeNi/NC@G). The P-FeNi/NC@G electrode exhibits a superior OER activity with an overpotential of 310 mV at 10 mA cm-2 and an ORR performance with a half-wave potential of 0.81 V. With P-FeNi/NC@G as the air cathode, the integrated all-solid-state rechargeable zinc-air battery presents a high open-circuit voltage of 1.53 V, a high peak power density of 159 mW cm-2, a small charge-discharge voltage gap of 0.73 V at 5 mA cm-2, as well as excellent long-term stability up to 144 cycles. This work not only expands the air cathode materials database but also develops a new co-doped synthesis method that can be utilized to fabricate a cathode with promoted catalytic efficiency, resulting in improved performance for an all-solid-state zinc-air battery.

Ultra-fast photodetectors based on high-mobility indium gallium antimonide nanowires.

Because of tunable bandgap and high carrier mobility, ternary III-V nanowires (NWs) have demonstrated enormous potential for advanced applications. However, the synthesis of large-scale and highly-crystalline InxGa1-xSb NWs is still a challenge. Here, we achieve high-density and crystalline stoichiometric InxGa1-xSb (0.09 < x < 0.28) NWs on amorphous substrates with the uniform phase-purity and <110 >-orientation via chemical vapor deposition. The as-prepared NWs show excellent electrical and optoelectronic characteristics, including the high hole mobility (i.e. 463 cm2 V-1 s-1 for In0.09Ga0.91Sb NWs) as well as broadband and ultrafast photoresponse over the visible and infrared optical communication region (1550 nm). Specifically, the In0.28Ga0.72Sb NW device yields efficient rise and decay times down to 38 and 53 µs, respectively, along with the responsivity of 6000 A W-1 and external quantum efficiency of 4.8 × 106 % towards 1550 nm regime. High-performance NW parallel-arrayed devices can also be fabricated to illustrate their large-scale device integrability for next-generation, ultrafast, high-responsivity and broadband photodetectors.

Novel Series of Quasi-2D Ruddlesden-Popper Perovskites Based on Short-Chained Spacer Cation for Enhanced Photodetection.

Quasi two-dimensional (2D) layered organic-inorganic perovskite materials (e.g., (BA)2(MA) n-1Pb nI3 n+1; BA = butylamine; MA = methylamine) have recently attracted wide attention because of their superior moisture stability as compared with three-dimensional counterparts. Inevitably, hydrophobic yet insulating long-chained organic cations improve the stability at the cost of hindering charge transport, leading to the unsatisfied performance of subsequently fabricated devices. Here, we reported the synthesis of quasi-2D ( iBA)2(MA) n-1Pb nI3 n+1 perovskites, where the relatively pure-phase ( iBA)2PbI4 and ( iBA)2MA3Pb4I13 films can be obtained. Because of the shorter-branched chain of iBA as compared with that of its linear equivalent ( n-butylamine, BA), the resulting ( iBA)2(MA) n-1Pb nI3 n+1 perovskites exhibit much enhanced photodetection properties without sacrificing their excellent stability. Through hot-casting, the optimized ( iBA)2(MA) n-1Pb nI3 n+1 perovskite films with n = 4 give the significantly improved crystallinity, demonstrating the high responsivity of 117.09 mA/W, large on-off ratio of 4.0 × 102, and fast response speed (rise and decay time of 16 and 15 ms, respectively). These figure-of-merits are comparable or even better than those of state-of-the-art quasi-2D perovskite-based photodetectors reported to date. Our work not only paves a practical way for future perovskite photodetector fabrication via modulation of their intrinsic material properties but also provides a direction for further performance enhancement of other perovskite optoelectronics.

Bitterness and antibacterial activities of constituents from Evodia rutaecarpa.

BACKGROUND: Bitter herbs are important in Traditional Chinese Medicine and the Electronic Tongue (e-Tongue) is an instrument that can be trained to evaluate bitterness of bitter herbs and their constituents. The aim of this research was to evaluate bitterness of limonoids and alkaloids from Evodia rutaecarpa to demonstrate that they are main bitter material basic of E. rutaecarpa. METHODS: Nine compounds, including limonoids, indoloquinazoline alkaloids and quinolone alkaloids, were isolated, identified and analyzed by the e-Tongue. Additionally, the antibacterial activities of the nine compounds were evaluated against E. coli and S. aureus. RESULTS: All the nine compounds had bitter taste and antibacterial activities to some extent. Among them, limonoids, which were the bitterest compounds, had greater antibacterial activities than alkaloids. And there is a positive correlation between bitter taste and antibacterial activities. CONCLUSIONS: It was confirmed in our study that limonoids, indoloquinazoline alkaloids and quinolone alkaloids are main bitter material basic of E. rutaecarpa based on two evaluation methods of e-Tongue and antibacterial experiment. In addition, the e-Tongue technique is a suitable new method to measure bitter degree in herbs.

Enhanced Self-Assembly of Crystalline, Large-Area, and Periodicity-Tunable TiO2 Nanotube Arrays on Various Substrates.

Due to their superior physical properties, titanium dioxide (TiO2) nanotube arrays are one of the most investigated nanostructure systems in materials science until now. However, it is still a great challenge to achieve damage-free techniques to realize controllable, cost-effective, and high-performance TiO2 nanotube arrays on both rigid and flexible substrates for different technological applications. In this work, we demonstrate a unique strategy to achieve self-assemble crystalline, large-area, and regular TiO2 nanotube arrays on various substrates via hybrid combination of conventional semiconductor processes. Besides the usual applications of TiO2 as carrier transport layers in thin-film electronic devices, we demonstrate that the periodic TiO2 nanotube arrays can show the effect of optical grating with large-area uniformity. Specifically, the fabricated nanotube geometries, such as the tube height, pitch, diameter, and wall thickness, as well as the crystallinity can be reliably controlled by varying the processing conditions. More importantly, utilizing these nanotube arrays in perovskite solar cells can further enhance the optical absorption, leading to improved power conversion efficiency. In contrast to other typical template-assisted fabrication approaches, we employ a soft template here, which would enable the construction of nanotube arrays without any significant damage associated with template removal. Furthermore, without the thermal restriction of underlying substrates, these crystalline nanotube arrays can be transferred to mechanically flexible substrates by a simple one-step method, which can expedite these nanotubes for potential utilization in other application domains.

Inverted Silicon Nanopencil Array Solar Cells with Enhanced Contact Structures.

Although three-dimensional nanostructured solar cells have attracted extensive research attention due to their superior broadband and omnidirectional light-harvesting properties, majority of them are still suffered from complicated fabrication processes as well as disappointed photovoltaic performances. Here, we employed our newly-developed, low-cost and simple wet anisotropic etching to fabricate hierarchical silicon nanostructured arrays with different solar cell contact design, followed by systematic investigations of their photovoltaic characteristics. Specifically, nano-arrays with the tapered tips (e.g. inverted nanopencils) are found to enable the more conformal top electrode deposition directly onto the nanostructures for better series and shunt conductance, but its insufficient film coverage at the basal plane would still restrict the charge carrier collection. In contrast, the low-platform contact design facilitates a substantial photovoltaic device performance enhancement of ~24%, as compared to the one of conventional top electrode design, due to the shortened current path and improved lateral conductance for the minimized carrier recombination and series resistance. This enhanced contact structure can not only maintain excellent photon-trapping behaviors of nanostructures, but also help to eliminate adverse impacts of these tapered nano-morphological features on the contact resistance, providing further insight into design consideration in optimizing the contact geometry for high-performance nanostructured photovoltaic devices.

Approaching the Hole Mobility Limit of GaSb Nanowires.

In recent years, high-mobility GaSb nanowires have received tremendous attention for high-performance p-type transistors; however, due to the difficulty in achieving thin and uniform nanowires (NWs), there is limited report until now addressing their diameter-dependent properties and their hole mobility limit in this important one-dimensional material system, where all these are essential information for the deployment of GaSb NWs in various applications. Here, by employing the newly developed surfactant-assisted chemical vapor deposition, high-quality and uniform GaSb NWs with controllable diameters, spanning from 16 to 70 nm, are successfully prepared, enabling the direct assessment of their growth orientation and hole mobility as a function of diameter while elucidating the role of sulfur surfactant and the interplay between surface and interface energies of NWs on their electrical properties. The sulfur passivation is found to efficiently stabilize the high-energy NW sidewalls of (111) and (311) in order to yield the thin NWs (i.e., <40 nm in diameters) with the dominant growth orientations of ⟨211⟩ and ⟨110⟩, whereas the thick NWs (i.e., >40 nm in diameters) would grow along the most energy-favorable close-packed planes with the orientation of ⟨111⟩, supported by the approximate atomic models. Importantly, through the reliable control of sulfur passivation, growth orientation and surface roughness, GaSb NWs with the peak hole mobility of ∼400 cm(2)V s(-1) for the diameter of 48 nm, approaching the theoretical limit under the hole concentration of ∼2.2 × 10(18) cm(-3), can be achieved for the first time. All these indicate their promising potency for utilizations in different technological domains.

High-Performance GaAs Nanowire Solar Cells for Flexible and Transparent Photovoltaics.

Among many available photovoltaic technologies at present, gallium arsenide (GaAs) is one of the recognized leaders for performance and reliability; however, it is still a great challenge to achieve cost-effective GaAs solar cells for smart systems such as transparent and flexible photovoltaics. In this study, highly crystalline long GaAs nanowires (NWs) with minimal crystal defects are synthesized economically by chemical vapor deposition and configured into novel Schottky photovoltaic structures by simply using asymmetric Au-Al contacts. Without any doping profiles such as p-n junction and complicated coaxial junction structures, the single NW Schottky device shows a record high apparent energy conversion efficiency of 16% under air mass 1.5 global illumination by normalizing to the projection area of the NW. The corresponding photovoltaic output can be further enhanced by connecting individual cells in series and in parallel as well as by fabricating NW array solar cells via contact printing showing an overall efficiency of 1.6%. Importantly, these Schottky cells can be easily integrated on the glass and plastic substrates for transparent and flexible photovoltaics, which explicitly demonstrate the outstanding versatility and promising perspective of these GaAs NW Schottky photovoltaics for next-generation smart solar energy harvesting devices.

Modulating the morphology and electrical properties of GaAs nanowires via catalyst stabilization by oxygen.

Nowadays, III-V compound semiconductor nanowires (NWs) have attracted extensive research interest because of their high carrier mobility favorable for next-generation electronics. However, it is still a great challenge for the large-scale synthesis of III-V NWs with well-controlled and uniform morphology as well as reliable electrical properties, especially on the low-cost noncrystalline substrates for practical utilization. In this study, high-density GaAs NWs with lengths >10 µm and uniform diameter distribution (relative standard deviation σ ∼ 20%) have been successfully prepared by annealing the Au catalyst films (4-12 nm) in air right before GaAs NW growth, which is in distinct contrast to the ones of 2-3 µm length and widely distributed of σ ∼ 20-60% of the conventional NWs grown by the H2-annealed film. This air-annealing process is found to stabilize the Au nanoparticle seeds and to minimize Ostwald ripening during NW growth. Importantly, the obtained GaAs NWs exhibit uniform p-type conductivity when fabricated into NW-arrayed thin-film field-effect transistors (FETs). Moreover, they can be integrated with an n-type InP NW FET into effective complementary metal oxide semiconductor inverters, capable of working at low voltages of 0.5-1.5 V. All of these results explicitly demonstrate the promise of these NW morphology and electrical property controls through the catalyst engineering for next-generation electronics.

[Research on bitter components from Coptis chinensis based on electronic tongue].

Isolated alkaloids from Coptis chinensis Franch. The compounds were identified as berberine, columbamine, groenlandicine, jatrorrhizine, magnoflorine, corydaldine and ferulic acid methylester. Then measured their bitter degree based on the electronic tongue and evaluated the antibacterial. The results based on the Electronic Tongue showed that berberine, columbamine, groenlandicine and jatrorrhizine have higher bitter degree than magnoflorine and corydaldine. And they also appeared better antibacterial activity on E. coli and S. aureus. The correlation coefficients between bitter degree and the two bacteria antibacterial activity were 0.983 and 0.911. So there was close relationship between the bitter degree and antibacterial activity of bitter components. Thus, it is confirmed further that bitter components are the material foundation of medicinal effectiveness of bitter herbs.

Effects of combination therapy with amlodipine and fosinopril administered at different times on blood pressure and circadian blood pressure pattern in patients with essential hypertension.

OBJECTIVE: The objective of our study was to compare the effects of a combination therapy with amlodipine and fosinopril administered concomitantly or at different times on blood pressure and circadian blood pressure pattern in subjects with essential hypertension. METHODS: 40 subjects with grade 1-2 essential hypertension and uncontrolled blood pressure after amlodipine or fosinopril monotherapy were randomized to combination therapy with amlodipine and fosinopril given in the morning and at bedtime (group A), or given concomitantly in the morning (group B). Clinic blood pressure values and 24-hour ambulatory blood pressure measurements were obtained before and after 4 weeks of treatment. RESULTS: After treatment, a reduction of 24-hour mean systolic and diastolic blood pressure was found in both groups. Subjects in group A showed a significant reduction in mean nocturnal systolic and diastolic blood pressure compared with group B (22.38/17.39 mmHg vs. 7.61/6.32 mmHg; P < 0.001). In group A a significant increase (5.68% and 4.57%, respectively; P < 0.05) was found in the diurnal/nocturnal blood pressure ratios of systolic and diastolic blood pressure and a slight reduction in the prevalence of non-dipping (< 10% decline in mean nocturnal vs. diurnal BP) from 53.85% to 30.77% (P = 0.428). Group B showed a significant reduction (5.68% and 5.76%; P < 0.01) in the diurnal/nocturnal systolic and diastolic blood pressure ratios and a slight increase in the prevalence of non-dipping from 38.46% to 53.85% (P = 0.428). CONCLUSION: Compared to concomitant administration of amlodipine and fosinopril in the morning, administration of the drugs at different times significantly decreased nocturnal blood pressure, increased the diurnal/nocturnal blood pressure ratio, and normalized the circadian blood pressure pattern. These findings indicate that chronotherapy may be an important strategy for optimizing blood pressure control and restoring the circadian blood pressure pattern.

An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation.

Daily subcutaneous administration of exogenous parathyroid hormone (PTH) promotes bone formation in patients with osteoporosis. Here we describe two novel, short-acting calcium-sensing receptor antagonists (SB-423562 and its orally bioavailable precursor, SB-423557) that elicit transient PTH release from the parathyroid gland in several preclinical species and in humans. In an ovariectomized rat model of bone loss, daily oral administration of SB-423557 promoted bone formation and improved parameters of bone strength at lumbar spine, proximal tibia and midshaft femur. Chronic administration of SB-423557 did not increase parathyroid cell proliferation in rats. In healthy human volunteers, single doses of intravenous SB-423562 and oral SB-423557 elicited transient elevations of endogenous PTH concentrations in a profile similar to that observed with subcutaneously administered PTH. Both agents were well tolerated in humans. Transient increases in serum calcium, an expected effect of increased parathyroid hormone concentrations, were observed post-dose at the higher doses of SB-423557 studied. These data constitute an early proof of principle in humans and provide the basis for further development of this class of compound as a novel, orally administered bone-forming treatment for osteoporosis.