Novel neuropharmacological activity of citrus lime (Citrus aurantifolia): A standardized lime peel supplement enhances non-rapid eye movement sleep by activating the GABA type A receptor.

Polyphenols have been well-established to exert sedative-hypnotic effects in psychopharmacology. Lime (Citrus aurantifolia) peel is rich in biologically active polyphenols; however, the effects of lime peel extract on sleep have not yet been demonstrated. A comparison was conducted in mice, between the sleep-promoting effects of a standardized lime peel supplement (SLPS) and a well-known hypnotic drug, zolpidem, and its hypnotic mechanism was investigated using in vivo and in vitro assays. The effects of SLPS on sleep were assessed using a pentobarbital-induced sleep test and sleep architecture analysis based on recording electroencephalograms and electromyograms. Additionally, a GABAA receptor binding assay, electrophysiological measurements, and in vivo animal models were used to elucidate the hypnotic mechanism. SLPS (200 and 400 mg/kg) was found to significantly decrease sleep latency and increase the amount of non-rapid eye movement sleep without altering delta activity. The hypnotic effects of SLPS were attributed to its flavonoid-rich ethyl acetate fraction. SLPS had a binding affinity to the GABA-binding site of the GABAA receptor and directly activated the GABAA receptors. The hypnotic effects and GABAA receptor activity of SLPS were completely blocked by bicuculline, a competitive antagonist of the GABAA receptor, in both in vitro and in vivo assays. To the best of our knowledge, this study is the first to demonstrate the hypnotic effects of SLPS, which acts via the GABA-binding site of the GABAA receptor. Our results suggest that lime peel, a by-product abundantly generated during juice processing, can potentially be used as a novel sedative-hypnotic.

Oxygen-defective electrostrictors for soft electromechanics.

Electromechanical metal oxides, such as piezoceramics, are often incompatible with soft polymers due to their crystallinity requirements, leading to high processing temperatures. This study explores the potential of ceria-based thin films as electromechanical actuators for flexible electronics. Oxygen-deficient fluorites, like cerium oxide, are centrosymmetric nonpiezoelectric crystalline metal oxides that demonstrate giant electrostriction. These films, deposited at low temperatures, integrate seamlessly with various soft substrates like polyimide and PET. Ceria thin films exhibit remarkable electrostriction (M33 > 10-16 m2 V-2) and inverse pseudo-piezo coefficients (e33 > 500 pmV-1), enabling large displacements in soft electromechanical systems. Our study explores resonant and off-resonant configurations in the low-frequency regime (<1 kHz), demonstrating versatility for three-dimensional and transparent electronics. This work advances the understanding of oxygen-defective metal oxide electromechanical properties and paves the way for developing versatile and efficient electromechanical systems for applications in biomedical devices, optical devices, and beyond.

Environmental Robustness and Resilience of Direct-Write Ultrasonic Transducers Made from P(VDF-TrFE) Piezoelectric Coating.

Conformability, lightweight, consistency and low cost due to batch fabrication in situ on host structures are the attractive advantages of ultrasonic transducers made of piezoelectric polymer coatings for structural health monitoring (SHM). However, knowledge about the environmental impacts of piezoelectric polymer ultrasonic transducers is lacking, limiting their widespread use for SHM in industries. The purpose of this work is to evaluate whether direct-write transducers (DWTs) fabricated from piezoelectric polymer coatings can withstand various natural environmental impacts. The ultrasonic signals of the DWTs and properties of the piezoelectric polymer coatings fabricated in situ on the test coupons were evaluated during and after exposure to various environmental conditions, including high and low temperatures, icing, rain, humidity, and the salt fog test. Our experimental results and analyses showed that it is promising for the DWTs made of piezoelectric P(VDF-TrFE) polymer coating with an appropriate protective layer to pass various operational conditions according to US standards.

Gigantic electro-chemo-mechanical properties of nanostructured praseodymium doped ceria.

Some oxygen defective fluorites are non-Newnham electrostrictors, i.e., the electromechanical response does not depend on their dielectric properties. Here, we show gigantic electrostriction in nanocrystalline 25 mol% praseodymium doped ceria (PCO) bulk ceramics. The material was fabricated with a field-assisted spark plasma sintering (SPS) process from high-purity nanoscale PCO powders (<20 nm). The SPS process consolidates the powders into a single-phase, highly dense material with a homogeneous microstructure and large grain boundary extension. Various thermally and chemically stable ionic defects are incorporated into the nanostructure, leading to superior electrical conductivity. The material shows an electrostriction strain coefficient (M33) of ∼10-16 m2 V-2 at frequencies below 100 Hz at room temperature. Such performance is comparable and even superior to Newnham's electrostrictors, such as ferroelectric ceramics and polymeric actuators. Comparative analysis with polycrystals suggests that nanostructured PCO possesses electromechanically active nanodomains of Pr3+-VO pairs. Such results are unexpected and open novel insights on non-Newnham electrostrictors.

Rice bran extract supplement improves sleep efficiency and sleep onset in adults with sleep disturbance: A randomized, double-blind, placebo-controlled, polysomnographic study.

We previously reported that rice bran extract supplement (RBS) administration to mice decreased sleep latency and induced non-rapid eye movement (NREM) sleep via inhibition of the histamine H1 receptor. Based on this, we performed the first clinical trial to investigate whether RBS would be beneficial to subjects with disturbed sleep. We performed a randomized, double-blinded, placebo-controlled, 2-week study. Fifty subjects with sleep disturbance were enrolled and received either RBS (1,000 mg/day) or placebo. Polysomnography was performed, and Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale were administered at the initiation and termination of the study. Compared with the placebo, RBS led to significant polysomnographic changes, including decreased sleep latency (adjusted, P = 0.047), increased total sleep time (P = 0.019), and improved sleep efficiency (P = 0.010). Additionally, the amount of stage 2 sleep significantly increased in the RBS group. When adjusted for caffeine intake, wakefulness after sleep onset, total wake time, and delta activity tended to decrease in the RBS group. RBS administration decreased ESS scores. There were no reported serious adverse events in both groups. RBS improved sleep in adults with sleep disturbance. Trial registration: WHO ICTRP, KCT0001893.

Atomic-Level Customization of 4 in. Transition Metal Dichalcogenide Multilayer Alloys for Industrial Applications.

Despite many encouraging properties of transition metal dichalcogenides (TMDs), a central challenge in the realm of industrial applications based on TMD materials is to connect the large-scale synthesis and reproducible production of highly crystalline TMD materials. Here, the primary aim is to resolve simultaneously the two inversely related issues through the synthesis of MoS2(1- x ) Se2 x ternary alloys with customizable bichalcogen atomic (S and Se) ratio via atomic-level substitution combined with a solution-based large-area compatible approach. The relative concentration of bichalcogen atoms in the 2D alloy can be effectively modulated by altering the selenization temperature, resulting in 4 in. scale production of MoS1.62 Se0.38 , MoS1.37 Se0.63 , MoS1.15 Se0.85 , and MoS0.46 Se1.54 alloys, as well as MoS2 and MoSe2 . Comprehensive spectroscopic evaluations for vertical and lateral homogeneity in terms of heteroatom distribution in the large-scale 2D TMD alloys are implemented. Se-stimulated strain effects and a detailed mechanism for the Se substitution in the MoS2 crystal are further explored. Finally, the capability of the 2D alloy for industrial application in nanophotonic devices and hydrogen evolution reaction (HER) catalysts is validated. Substantial enhancements in the optoelectronic and HER performances of the 2D ternary alloy compared with those of its binary counterparts, including pure-phase MoS2 and MoSe2 , are unambiguously achieved.

High energy electron beam stimulated nanowelding of silver nanowire networks encapsulated with graphene for flexible and transparent electrodes.

Low-dimensional nanostructures and their complementary hybridization techniques are in the vanguard of technological advances for applications in transparent and flexible nanoelectronics due to the intriguing electrical properties related to their atomic structure. In this study, we demonstrated that welding of Ag nanowires (NWs) encapsulated in graphene was stimulated by flux-optimized, high-energy electron beam irradiation (HEBI) under ambient conditions. This methodology can inhibit the oxidation of Ag NWs which is induced by the inevitably generated reactive ozone as well as improve of their electrical conductivity. We have systematically explored the effects of HEBI on Ag NWs and graphene. The optimized flux for HEBI welding of the Ag NWs with graphene was 150 kGy, which decreased the sheet resistance of the graphene/Ag NWs to 12 Ohm/sq. Following encapsulation with graphene, the initial chemical states of the Ag NWs were well-preserved after flux-tuned HEBI, whereas graphene underwent local HEBI-induced defect generation near the junction area. We further employed resonant Raman spectroscopy to follow the structural evolution of the sacrificial graphene in the hybrid film after HEBI. Notably, the sheet resistance of the welded Ag NWs encapsulated with graphene after HEBI was well-maintained even after 85 days.

Attachable piezoelectric nanogenerators using collision-induced strain of vertically grown hollow MoS2 nanoflakes.

Piezoelectric materials convert external mechanical force into electrical energy, due to the breaking of the centrosymmetry of the atomic structure. Piezoelectricity-based nano-generators (PNGs) based on two-dimensional transition metal dichalcogenides (TMDs) can generate electrical energy stably by the piezoelectric effect at their nanoscale thickness. However, the commercialization of TMD-based PNGs is limited by their poor piezoelectric performance and microscale energy harvesting. Here, we present the first centimeter-scale PNGs based on molybdenum disulfide (MoS2) nanosheets with vertically grown hollow MoS2 nanoflakes (v-MoS2 NFs) obtained by chemical vapor deposition for energy harvesting from human motions. The collision of v-MoS2 NFs with a preferred odd-atomic-layer number and their 2H antiparallel phase leads to efficient electrical energy generation during the bending movement. Further, basal MoS2 films with v-MoS2 NFs are transferred onto flexible substrates via conventional polymer-assisted methods for the fabrication of attachable and wearable piezoelectric power generators.

Phlorotannin supplement decreases wake after sleep onset in adults with self-reported sleep disturbance: A randomized, controlled, double-blind clinical and polysomnographic study.

Our previous study demonstrated that phlorotannin supplement had a sleep-promoting effect in rodents. In the present study, we investigated whether the phlorotannin supplement could improve sleep in subjects with self-reported sleep disturbances. In a randomized, double-blind, placebo-controlled trial, 24 subjects consumed either a placebo or phlorotannin supplement (500 mg/day) for 1 week, 30-60 min prior to bedtime. Sleep parameters were assessed at baseline and at 1 week with sleep questionnaires and polysomnography. At the end of the treatment period, the complete sets of sleep parameters from 20 subjects. Phlorotannin resulted in a significant increase in "Sleep duration" scores compared to the placebo (p = .044), although there were no significant differences on the total PSQI scores. Polysomnography revealed that wakefulness after sleep onset was significantly lower in the phlorotannin group compared to the placebo group (phlorotannin vs. placebo, -25.5 ± 30.5 vs. -1.7 ± 14.9; p = .045) as well as total wake time (phlorotannin vs. placebo, -0.9 ± 3.0 vs. -6.1 ± 6.8; p = .048). Additionally, the respiratory disturbance index during supine rapid eye movement sleep was significantly lower in the phlorotannin group (p = .035). There were no serious adverse effects in either group. Our data suggest that the phlorotannin supplement improved sleep maintenance (WHO ICTRP: KCT0001892).

Roll-to-Roll Production of Layer-Controlled Molybdenum Disulfide: A Platform for 2D Semiconductor-Based Industrial Applications.

A facile methodology for the large-scale production of layer-controlled MoS2 layers on an inexpensive substrate involving a simple coating of single source precursor with subsequent roll-to-roll-based thermal decomposition is developed. The resulting 50 cm long MoS2 layers synthesized on Ni foils possess excellent long-range uniformity and optimum stoichiometry. Moreover, this methodology is promising because it enables simple control of the number of MoS2 layers by simply adjusting the concentration of (NH4 )2 MoS4 . Additionally, the capability of the MoS2 for practical applications in electronic/optoelectronic devices and catalysts for hydrogen evolution reaction is verified. The MoS2 -based field effect transistors exhibit unipolar n-channel transistor behavior with electron mobility of 0.6 cm2 V-1 s-1 and an on-off ratio of ≈10³. The MoS2 -based visible-light photodetectors are fabricated in order to evaluate their photoelectrical properties, obtaining an 100% yield for active devices with significant photocurrents and extracted photoresponsivity of ≈22 mA W-1 . Moreover, the MoS2 layers on Ni foils exhibit applicable catalytic activity with observed overpotential of ≈165 mV and a Tafel slope of 133 mV dec-1 . Based on these results, it is envisaged that the cost-effective methodology will trigger actual industrial applications, as well as novel research related to 2D semiconductor-based multifaceted applications.

A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population.

OBJECTIVE: Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population. METHODS: We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results. RESULTS: In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10-6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10-6) and rs9390170 (OR=0.6778, p=7.67×10-6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10-18) in BTBD9 was associated with RLS. CONCLUSION: From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.

Strain-Gradient Effect in Gas Sensors Based on Three-Dimensional Hollow Molybdenum Disulfide Nanoflakes.

A novel three-dimensional transition metal dichalcogenide (TMD) structure consisting of seamless hollow nanoflakes on two-dimensional basal layers was synthesized by a one-step chemical vapor deposition method. Here, we demonstrate that the as-grown nanoflakes are formed on an organic promoter layer which served as a positive template and are swollen at the grain boundaries by the bubbling effect. TMD nanosheets with hollow nanoflakes are successfully applied as chemical sensors, and it was found that their gas adsorption property is strongly related to the internal strain gradient resulting from the variation in the lattice parameter. This result is consistent with the theoretical prediction in previous studies. Our chemical vapor deposition-based approach is an efficient way to generate TMD-based nanostructures over a large surface area for various practical applications such as chemical sensors.

Flexible Piezoelectric Generators by Using the Bending Motion Method of Direct-Grown-PZT Nanoparticles on Carbon Nanotubes.

Recently, composite-type nanogenerators (NGs) formed from piezoelectric nanostructures and multi-walled carbon nanotubes (CNTs), have become one of the excellent candidates for future energy harvesting because of their ability to apply the excellent electrical and mechanical properties of CNTs. However, the synthesis of NG devices with a high proportion of piezoelectric materials and a low polymer content, such as of polydimethylsiloxane (PDMS), continues to be problematic. In this work, high-piezoelectric-material-content flexible films produced from Pb(Zr,Ti)O3 (PZT)-atomically-interconnected CNTs and polytetrafluoroethylene (PTFE) are presented. Various physical and chemical characterization techniques are employed to examine the morphology and structure of the materials. The direct growth of the piezoelectric material on the CNTs, by stirring the PZT and CNT mixed solution, results in various positive effects, such as a high-quality dispersion in the polymer matrix and addition of flexoelectricity to piezoelectricity, resulting in the enhancement of the output voltage by an external mechanical force. The NGs repeatedly generate an output voltage of 0.15 V. These results present a significant step toward the application of NGs using piezoelectric nanocomposite materials.

Toward Arbitrary-Direction Energy Harvesting through Flexible Piezoelectric Nanogenerators Using Perovskite PbTiO3 Nanotube Arrays.

New fiber-type piezoelectric nanogenerator devices consisting of radially aligned perovskite PbTiO3 nanotubes are designed for energy harvesting from arbitrary mechanical motion. The free-standing fiber-type nanogenerators generate constant amount of electric power by bending or wind motion regardless of direction, thus, extending the possibility of their practical applications.

Nanogenerators consisting of direct-grown piezoelectrics on multi-walled carbon nanotubes using flexoelectric effects.

We report the first attempt to prepare a flexoelectric nanogenerator consisting of direct-grown piezoelectrics on multi-walled carbon nanotubes (mwCNT). Direct-grown piezoelectrics on mwCNTs are formed by a stirring and heating method using a Pb(Zr0.52Ti0.48)O3 (PZT)-mwCNT precursor solution. We studied the unit cell mismatch and strain distribution of epitaxial PZT nanoparticles, and found that lattice strain is relaxed along the growth direction. A PZT-mwCNT nanogenerator was found to produce a peak output voltage of 8.6 V and an output current of 47 nA when a force of 20 N is applied. Direct-grown piezoelectric nanogenerators generate a higher voltage and current than simple mixtures of PZT and CNTs resulting from the stronger connection between PZT crystals and mwCNTs and an enhanced flexoelectric effect caused by the strain gradient. These experiments represent a significant step toward the application of nanogenerators using piezoelectric nanocomposite materials.

Wafer-Scale, Homogeneous MoS2 Layers on Plastic Substrates for Flexible Visible-Light Photodetectors.

An appropriate solution is suggested for synthesizing wafer-scale, continuous, and stoichiometric MoS2 layers with spatial homogeneity at the low temperature of 450 °C. It is also demonstrated that the MoS2 -based visible-light photodetector arrays are both fabricated on 4 inch SiO2 /Si wafer and polyimide films, revealing 100% active devices with a narrow photocurrent distribution and excellent mechanical durability.

Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor.

RATIONALE: In psychopharmacology, researchers have been interested in the hypnotic effects of terrestrial plant polyphenols and their synthetic derivatives. Phlorotannins, a marine plant polyphenol, could have potential as a source of novel hypnotic drugs. OBJECTIVES: The effects of phlorotannins and major phlorotannin constituent eckstolonol on sleep-wake profiles in mice were evaluated in comparison with diazepam, and their hypnotic mechanism was also investigated. METHODS: The effects of phlorotannin preparation (PRT) and eckstolonol orally given on sleep-wake profiles were measured by recording electroencephalograms (EEG) and electromyograms in C57BL/6N mice. Flumazenil, a GABAA-benzodiazepine (BZD) receptor antagonist, was injected 15 min before PRT and eckstolonol to reveal its hypnotic mechanism. RESULTS: PRT administration (>250 mg/kg) produced a significant decrease in sleep latency and an increase in the amount of non-rapid eye movement sleep (NREMS). Eckstolonol significantly decreased sleep latency (>12.5 mg/kg) and increased the amount of NREMS (50 mg/kg). PRT and eckstolonol had no effect on EEG power density of NREMS. The hypnotic effects of PRT or eckstolonol were completely abolished by pretreatment with flumazenil. CONCLUSIONS: We demonstrated that phlorotannins promote NREMS by modulating the BZD site of the GABAA receptor. These results suggest that phlorotannins can be potentially used as an herbal medicine for insomnia and as a promising structure for developing novel sedative-hypnotics.

Effects of sintering temperature on the pyrochlore phase in PZT nanotubes and their transformation to the perovskite phase by coating with PbO multilayers.

We report the phase evolution of Pb(Zr0.52Ti0.48)O3 nanotubes (PZT-NTs), from the pyrochlore to perovskite phase, with an outer diameter of about 420 nm and a wall thickness of about 10 nm. The PZT-NTs were fabricated in pores of porous anodic alumina membrane (PAM) using a spin coating of PZT sol-gel solution and subsequent annealing at 500-700 degrees C in oxygen gas. The pyrochlore phase was found to be formed at 500 degrees C, and also found not to be transformed into the perovskite phase, even though annealing was performed at higher temperatures to 700 degrees C. Elementary distribution analysis of PZT-NTs embedded in PAM reveal that Pb diffusion from nanotubes into pore walls of PAM is one of the main reasons. By employing firstly an additional PbO coating on the pyrochlore nanotubes and then subsequent annealing at 700 degrees C, we have successfully achieved an almost pure perovskite phase in nanotubes. These results suggest that PbO acts as a Pb-compensation agent in the Pb- deficient PZT-NTs. Moreover, our method can be used in the synthesis of all metal-oxide materials, including volatile elements.

Glass-embedded two-dimensional silicon photonic crystal devices with a broad bandwidth waveguide and a high quality nanocavity.

To enhance the mechanical stability of a two-dimensional photonic crystal slab structure and maintain its excellent performance, we designed a glass-embedded silicon photonic crystal device consisting of a broad bandwidth waveguide and a nanocavity with a high quality (Q) factor, and then fabricated the structure using spin-on glass (SOG). Furthermore, we showed that the refractive index of the SOG could be tuned from 1.37 to 1.57 by varying the curing temperature of the SOG. Finally, we demonstrated a glass-embedded heterostructured cavity with an ultrahigh Q factor of 160,000 by adjusting the refractive index of the SOG.

Ferroelectricity in highly ordered arrays of ultra-thin-walled Pb(Zr,Ti)O3 nanotubes composed of nanometer-sized perovskite crystallites.

We report the first unambiguous ferroelectric properties of ultra-thin-walled Pb(Zr,Ti)O 3 (PZT) nanotube arrays, each with 5 nm thick walls and outer diameters of 50 nm. Ferroelectric switching behavior with well-saturated hysteresis loops is observed in these ferroelectric PZT nanotubes with P r and E c values of about 1.5 microC cm (-2) and 86 kV cm (-1), respectively, for a maximum applied electric field of 400 kV cm (-1). These PZT nanotube arrays (10 (12) nanotubes cm (-2)) might provide a competitive approach toward the development of three-dimensional capacitors for the terabyte ferroelectric random access memory.