FSLLRY-NH2, a protease-activated receptor 2 (PAR2) antagonist, activates mas-related G protein-coupled receptor C11 (MrgprC11) to induce scratching behaviors in mice.

AIMS: Protease-activated receptor 2 (PAR2), a type of G protein-coupled receptor (GPCR), plays a significant role in pathophysiological conditions such as inflammation. A synthetic peptide SLIGRL-NH2 (SLIGRL) can activate PAR2, while FSLLRY-NH2 (FSLLRY) is an antagonist. A previous study showed that SLIGRL activates both PAR2 and mas-related G protein-coupled receptor C11 (MrgprC11), a different type of GPCR expressed in sensory neurons. However, the impact of FSLLRY on MrgprC11 and its human ortholog MRGPRX1 was not verified. Hence, the present study aims to verify the effect of FSLLRY on MrgprC11 and MRGPRX1. METHODS: The calcium imaging technique was applied to determine the effect of FSLLRY in HEK293T cells expressing MrgprC11/MRGPRX1 or dorsal root ganglia (DRG) neurons. Scratching behavior was also investigated in wild-type and PAR2 knockout mice after injecting FSLLRY. KEY FINDINGS: It was surprisingly discovered that FSLLRY specifically activates MrgprC11 in a dose-dependent manner, but not other MRGPR subtypes. Furthermore, FSLLRY also moderately activated MRGPRX1. FSLLRY stimulates downstream pathways including Gαq/11, phospholipase C, IP3 receptor, and TRPC ion channels to evoke an increase in the intracellular calcium levels. The molecular docking analysis predicted that FSLLRY interacts with the orthosteric binding pocket of MrgprC11 and MRGPRX1. Finally, FSLLRY activated primary cultures of mouse sensory neurons, and induced scratching behaviors in mice. SIGNIFICANCE: The present study has revealed that FSLLRY is capable of triggering itch sensation through activation of MrgprC11. This finding highlights the importance of considering the unexpected activation of MRGPRs in future therapeutic approaches aimed at the inhibition of PAR2.

Anti-Inflammatory, Antioxidative, and Nitric Oxide-Scavenging Activities of a Quercetin Nanosuspension with Polyethylene Glycol in LPS-Induced RAW 264.7 Macrophages.

Quercetin (Qu) is a dietary antioxidant and a member of flavonoids in the plant polyphenol family. Qu has a high ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) molecules; hence, exhibiting beneficial effects in preventing obesity, diabetes, cancer, cardiovascular diseases, and inflammation. However, quercetin has low bioavailability due to poor water solubility, low absorption, and rapid excretion from the body. To address these issues, the usage of Qu nanosuspensions can improve physical stability, solubility, and pharmacokinetics. Therefore, we developed a Qu and polyethylene glycol nanosuspension (Qu-PEG NS) and confirmed its interaction by Fourier transform infrared analysis. Qu-PEG NS did not show cytotoxicity to HaCaT and RAW 264.7 cells. Furthermore, Qu-PEG NS effectively reduced the nitrogen oxide (NO) production in lipopolysaccharide (LPS)-induced inflammatory RAW 264.7 cells. Additionally, Qu-PEG NS effectively lowered the levels of COX-2, NF-κB p65, and IL-1ß in the LPS-induced inflammatory RAW 264.7 cells. Specifically, Qu-PEG NS exhibited anti-inflammatory properties by scavenging the ROS and RNS and mediated the inhibition of NF-κB signaling pathways. In addition, Qu-PEG NS had a high antioxidant effect and antibacterial activity against Escherichia coli and Bacillus cereus. Therefore, the developed novel nanosuspension showed comparable antioxidant, anti-inflammatory, and antibacterial functions and may also improve solubility and physical stability compared to raw quercetin.

Robust Co alloy design for Co interconnects using a self-forming barrier layer.

With recent rapid increases in Cu resistivity, RC delay has become an important issue again. Co, which has a low electron mean free path, is being studied as beyond Cu metal and is expected to minimize this increase in resistivity. However, extrinsic time-dependent dielectric breakdown has been reported for Co interconnects. Therefore, it is necessary to apply a diffusion barrier, such as the Ta/TaN system, to increase interconnect lifetimes. In addition, an ultrathin diffusion barrier should be formed to occupy as little area as possible. This study provides a thermodynamic design for a self-forming barrier that provides reliability with Co interconnects. Since Cr, Mn, Sn, and Zn dopants exhibited surface diffusion or interfacial stable phases, the model constituted an effective alloy design. In the Co-Cr alloy, Cr diffused into the dielectric interface and reacted with oxygen to provide a self-forming diffusion barrier comprising Cr2O3. In a breakdown voltage test, the Co-Cr alloy showed a breakdown voltage more than 200% higher than that of pure Co. The 1.2 nm ultrathin Cr2O3 self-forming barrier will replace the current bilayer barrier system and contribute greatly to lowering the RC delay. It will realize high-performance Co interconnects with robust reliability in the future.

Thermodynamically driven self-formation of Ag nanoparticles in Zn-embedded carbon nanofibers for efficient electrochemical CO2 reduction.

The electrochemical CO2 reduction reaction (CO2RR), which converts CO2 into value-added feedstocks and renewable fuels, has been increasingly studied as a next-generation energy and environmental solution. Here, we report that single-atom metal sites distributed around active materials can enhance the CO2RR performance by controlling the Lewis acidity-based local CO2 concentration. By utilizing the oxidation Gibbs free energy difference between silver (Ag), zinc (Zn), and carbon (C), we can produce Ag nanoparticle-embedded carbon nanofibers (CNFs) where Zn is atomically dispersed by a one-pot, self-forming thermal calcination process. The CO2RR performance of AgZn-CNF was investigated by a flow cell with a gas diffusion electrode (GDE). Compared to Ag-CNFs without Zn species (53% at -0.85 V vs. RHE), the faradaic efficiency (FE) of carbon monoxide (CO) was approximately 20% higher in AgZn-CNF (75% at -0.82 V vs. RHE) with 1 M KOH electrolyte.

Electrochemical oxidation of boron-doped nickel-iron layered double hydroxide for facile charge transfer in oxygen evolution electrocatalysts.

The oxygen evolution reaction (OER) is the key reaction in water splitting systems, but compared with the hydrogen evolution reaction (HER), the OER exhibits slow reaction kinetics. In this work, boron doping into nickel-iron layered double hydroxide (NiFe LDH) was evaluated for the enhancement of OER electrocatalytic activity. To fabricate boron-doped NiFe LDH (B:NiFe LDH), gaseous boronization, a gas-solid reaction between boron gas and NiFe LDH, was conducted at a relatively low temperature. Subsequently, catalyst activation was performed through electrochemical oxidation for maximization of boron doping and improved OER performance. As a result, it was possible to obtain a remarkably reduced overpotential of 229 mV at 10 mA cm-2 compared to that of pristine NiFe LDH (315 mV) due to the effect of facile charge-transfer resistance by boron doping and improved active sites by electrochemical oxidation.

Metal-organic Framework-driven Porous Cobalt Disulfide Nanoparticles Fabricated by Gaseous Sulfurization as Bifunctional Electrocatalysts for Overall Water Splitting.

Both high activity and mass production potential are important for bifunctional electrocatalysts for overall water splitting. Catalytic activity enhancement was demonstrated through the formation of CoS2 nanoparticles with mono-phase and extremely porous structures. To fabricate porous structures at the nanometer scale, Co-based metal-organic frameworks (MOFs), namely a cobalt Prussian blue analogue (Co-PBA, Co3[Co(CN)6]2), was used as a porous template for the CoS2. Then, controlled sulfurization annealing converted the Co-PBA to mono-phase CoS2 nanoparticles with ~ 4 nm pores, resulting in a large surface area of 915.6 m2 g-1. The electrocatalysts had high activity for overall water splitting, and the overpotentials of the oxygen evolution reaction and hydrogen evolution reaction under the operating conditions were 298 mV and -196 mV, respectively, at 10 mA cm-2.

Anion Extraction-Induced Polymorph Control of Transition Metal Dichalcogenides.

Controlled phase conversion in polymorphic transition metal dichalcogenides (TMDs) provides a new synthetic route for realizing tunable nanomaterials. Most conversion methods from the stable 2H to metastable 1T phase are limited to kinetically slow cation insertion into atomically thin layered TMDs for charge transfer from intercalated ions. Here, we report that anion extraction by the selective reaction between carbon monoxide (CO) and chalcogen atoms enables predictive and scalable TMD polymorph control. Sulfur vacancy, induced by anion extraction, is a key factor in molybdenum disulfide (MoS2) polymorph conversion without cation insertion. Thermodynamic MoS2-CO-CO2 ternary phase diagram offers a processing window for efficient sulfur vacancy formation with precisely controlled MoS2 structures from single layer to multilayer. To utilize our efficient phase conversion, we synthesize vertically stacked 1T-MoS2 layers in carbon nanofibers, which exhibit highly efficient hydrogen evolution reaction catalytic activity. Anion extraction induces the polymorph conversion of tungsten disulfide (WS2) from 2H to 1T. This reveals that our method can be utilized as a general polymorph control platform. The versatility of the gas-solid reaction-based polymorphic control will enable the engineering of metastable phases in 2D TMDs for further applications.

Thermally Stable Amorphous Oxide-based Schottky Diodes through Oxygen Vacancy Control at Metal/Oxide Interfaces.

Amorphous oxide semiconductor (AOS)-based Schottky diodes have been utilized for selectors in crossbar array memories to improve cell-to-cell uniformity with a low-temperature process. However, thermal instability at interfaces between the AOSs and metal electrodes can be a critical issue for the implementation of reliable Schottky diodes. Under post-fabrication annealing, an excessive redox reaction at the ohmic interface can affect the bulk region of the AOSs, inducing an electrical breakdown of the device. Additionally, structural relaxation (SR) of the AOSs can increase the doping concentration at the Schottky interface, which results in a degradation of the rectifying performance. Here, we improved the thermal stability at AOS/metal interfaces by regulating the oxygen vacancy (VO) concentration at both sides of the contact. For a stable quasi-ohmic contact, a Cu-Mn alloy was introduced instead of a single component reactive metal. As Mn only takes up O in amorphous In-Ga-Zn-O (a-IGZO), excessive VO generation in bulk region of a-IGZO can be prevented. At the Schottky interfaces, the barrier characteristics were not degraded by thermal annealing as the Ga concentration in a-IGZO increased. Ga not only reduces the inherent VO concentration but also retards SR, thereby suppressing tunneling conduction and enhancing the thermal stability of devices.