Robust 2D layered MXene matrix-boron carbide hybrid films for neutron radiation shielding.

Large-scale fabrication of neutron-shielding films with flexible or complex shapes is challenging. Uniform and high boron carbide (B4C) filler loads with sufficient workability are needed to achieve good neutron-absorption capacity. Here, we show that a two-dimensional (2D) Ti3C2Tx MXene hybrid film with homogeneously distributed B4C particles exhibits high mechanical flexibility and anomalous neutron-shielding properties. Layered and solution-processable 2D Ti3C2Tx MXene flakes serve as an ideal robust and flexible matrix for high-content B4C fillers (60 wt.%). In addition, the preparation of a scalable neutron shielding MXene/B4C hybrid paint is demonstrated. This composite can be directly integrated with various large-scale surfaces (e.g., stainless steel, glass, and nylon). Because of their low thickness, simple and scalable preparation method, and an absorption capacity of 39.8% for neutrons emitted from a 241Am-9Be source, the 2D Ti3C2Tx MXene hybrid films are promising candidates for use in wearable and lightweight applications.

Effect of endogenous substance P on visceral afferent signal integration in the nucleus tractus solitaries of rat brainstem slices.

In the first synapse of the blood-pressure-regulating pathway, a neurokinin (NK) family peptide substance P (SP) is release with an excitatory neurotransmitter, glutamate, to enhance the sensitivity of the baroreflex responses. However, the underlying mechanisms of action are not yet well understood. The effects of NK receptor antagonists and agonists on solitary tract stimulation-evoked excitatory postsynaptic responses were recorded using whole-cell patch-clamp recordings of neurons in the medial portion of the nucleus tractus solitarius (mNTS) in the brainstem. SP reduced the amplitude of the evoked excitatory postsynaptic currents (eEPSCs) and shifted the holding current inward, in a dose-dependent manner. The concentrations of SP needed to induce such responses were different between capsaicin-sensitive unmyelinated (C-type) and capsaicin-resistant myelinated (A-type) neurons. The perfusion of a NK1 receptor antagonist, sendide, reduced the amplitude of eEPSCs in all tested neurons but did not affect the levels of the holding current. A Neurokinin type 1 receptor (NK1 receptor) agonist, [Sar9, Met(O2)11]-SP, reduced the amplitude of the eEPSCs and shifted the holding current inward in capsaicin-resistant neurons; however, it failed to induce any significant changes in the capsaicin-sensitive neurons. Furthermore, a selective Neurokinin type 3 receptor (NK3 receptor) antagonist, SB223412, failed to induce any changes in any tested neuron. In current-clamp experiments, sendide reduced solitary tract (ST)-stimulation evoked firing of action potentials in both A- and C-type neurons. [Sar9, Met(O2)11]-SP suppressed the firing of the action potentials in C-type but not A-type neurons. In spontaneous synaptic recordings, SP reduced frequency of the sEPSCs in CAP sensitive neuron but NK1 agonist reduced at capsaicin resistant neurons. Taken together, the findings show that ST activation leads to the co-transmission of SP and glutamate and enhances baroreflex sensitivity by potentiating the amplitude of eEPSC in an NK1 receptor activity-dependent manner.

The effect of ginger extract on cisplatin-induced acute anorexia in rats.

Cisplatin is a platinum-based chemotherapeutic agent widely used to treat various cancers. However, several side effects have been reported in treated patients. Among these, acute anorexia is one of the most severe secondary effects. In this study, a single oral administration of 100 or 500 mg/kg ginger extract (GE) significantly alleviated the cisplatin-induced decrease in food intake in rats. However, these body weight and water intake decreases were reversed in the 100 mg/kg group rats. To elucidate the underlying mechanism of action, serotonin (5-HT) and 5-HT2C, 3A, and 4 receptors in the nodose ganglion of the vagus nerve were investigated. The results showed that cisplatin-induced increases in serotonin levels in both the blood and nodose ganglion tissues were significantly decreased by100 and 500 mg/kg of GE administration. On 5-HT receptors, 5-HT3A and 4, but not 2C receptors, were affected by cisplatin, and GE 100 and 500 mg/kg succeeded in downregulating the evoked upregulated gene of these receptors. Protein expression of 5-HT3A and 4 receptors were also reduced in the 100 mg/kg group. Furthermore, the injection of 5-HT3A, and 4 receptors antagonists (palonostron, 0.1 mg/kg, i.p.; piboserod, 1 mg/kg, i.p., respectively) in cisplatin treated rats prevented the decrease in food intake. Using high-performance liquid chromatography (HPLC) analysis, [6]-gingerol and [6]-shogaol were identified and quantified as the major components of GE, comprising 4.12% and 2.15% of the GE, respectively. Although [6]-gingerol or [6]-shogaol alone failed to alleviate the evoked anorexia, when treated together, the effect was significant on the cisplatin-induced decrease in food intake. These results show that GE can be considered a treatment option to alleviate cisplatin-induced anorexia.

Fabrication of p-type 2D single-crystalline transistor arrays with Fermi-level-tuned van der Waals semimetal electrodes.

High-performance p-type two-dimensional (2D) transistors are fundamental for 2D nanoelectronics. However, the lack of a reliable method for creating high-quality, large-scale p-type 2D semiconductors and a suitable metallization process represents important challenges that need to be addressed for future developments of the field. Here, we report the fabrication of scalable p-type 2D single-crystalline 2H-MoTe2 transistor arrays with Fermi-level-tuned 1T'-phase semimetal contact electrodes. By transforming polycrystalline 1T'-MoTe2 to 2H polymorph via abnormal grain growth, we fabricated 4-inch 2H-MoTe2 wafers with ultra-large single-crystalline domains and spatially-controlled single-crystalline arrays at a low temperature (~500 °C). Furthermore, we demonstrate on-chip transistors by lithographic patterning and layer-by-layer integration of 1T' semimetals and 2H semiconductors. Work function modulation of 1T'-MoTe2 electrodes was achieved by depositing 3D metal (Au) pads, resulting in minimal contact resistance (~0.7 kΩ·µm) and near-zero Schottky barrier height (~14 meV) of the junction interface, and leading to high on-state current (~7.8 µA/µm) and on/off current ratio (~105) in the 2H-MoTe2 transistors.

Substance P Increases the Excitability of Dorsal Motor Nucleus of the Vagus Nerve via Inhibition of Potassium Channels.

Increases in the substance P (SP) concentration in the medial portion of the dorsal motor nucleus of the vagus nerve (mDMV) in the brainstem are closely associated with chemotherapy induced nausea and vomiting (CINV). However, the underlying cellular and molecular mechanisms of action are not well understood. In this study, we investigated the effects of SP on mDMV neurons using whole-cell patch-clamp recordings from rat brainstem slices. Application of different concentrations of SP induced tonic and phasic responses. Submicromolar concentrations of induced an inward shift of the holding current by increasing membrane input resistance. The response was mimicked by acidification of the extracellular solution and inhibited by a neurokinin type 1 receptor antagonist. These responses have equilibrium potentials close to the K+ equilibrium potential. In addition, a TWIK-related acid-sensitive K+ channel 3 (TASK-3) inhibitor, PK-THPP, induced responses similar to those produced by submicromolar SP concentrations. Micromolar concentrations of SP facilitated γ-aminobutyric acid (GABA) release but diminished glutamate release; these changes were blocked by a GABA B receptor antagonist and a neurokinin type 3 receptor antagonist, respectively. In current-clamp recordings, submicromolar SP concentrations increased neuronal excitability by depolarizing membrane potentials. However, neither the increase in SP concentration to the micromolar range nor the addition of GABA A and ionotropic glutamate receptor antagonists affected neuronal excitability. Thus, SP increases the excitability of mDMV neurons by inhibiting K+ conductance.

Bee Venom Acupuncture Attenuates Oxaliplatin-Induced Neuropathic Pain by Modulating Action Potential Threshold in A-Fiber Dorsal Root Ganglia Neurons.

Oxaliplatin is a third-generation platinum-based chemotherapeutic drug widely used in colorectal cancer treatment. Although potent against this tumor, it can induce cold and mechanical allodynia even after a single injection. The currently used drugs to attenuate this allodynia can also cause unwanted effects, which limit their use. Bee venom acupuncture (BVA) is widely used in Korean medicine to treat pain. Although the effect of BVA on oxaliplatin-induced neuropathic pain has been addressed in many studies, its action on dorsal root ganglia (DRG) neurons has never been investigated. A single oxaliplatin injection (6 mg/kg, intraperitoneally) induced cold and mechanical allodynia, and BVA (0.1 and 1 mg/kg, subcutaneous, ST36) dose-dependently decreased allodynia in rats. On acutely dissociated lumbar 4-6 DRG neurons, 10 min application of oxaliplatin (100 µM) shifted the voltage-dependence of sodium conductance toward negative membrane potentials in A- but not C-fibers. The resting membrane potential remained unchanged, but the action potential threshold decreased significantly compared to that of the control (p < 0.05). However, 0.1 µg/mL of BVA administration increased the lowered action potential threshold. In conclusion, these results suggest that BVA may attenuate oxaliplatin-induced neuropathic pain by altering the action potential threshold in A-fiber DRG neurons.

Light Engineering in Nanometer Space.

Significant advances have been made in photonic integrated circuit technology, similar to the development of electronic integrated circuits. However, the miniaturization of cavity resonators, which are the essential components of photonic circuits, still requires considerable improvement. Over the past decades, various optical cavities have been utilized to implement next-generation light sources in photonic circuits with low energy, high data traffic, and integrable physical sizes. Nevertheless, it has been difficult to reduce the size of most commercialized cavities beyond the diffraction limit while maintaining high performance. Herein, recent advancements in subwavelength metallic cavities that can improve performance, even with the use of lossy plasmonic modes, are reviewed. The discussion is divided in three parts according to light engineering methods: subwavelength metal-clad cavities engineered using intermediate dielectric cladding; implementation of plasmonic cavities and waveguides using plasmonic crystals; and development of deep-subwavelength plasmonic waveguides and cavities using geometric engineering. A direction for further developments in photonic integrated circuit technology is also discussed, along with its practical application.

Extreme field confinement in zigzag plasmonic crystals.

We propose extreme field confinement in a zigzag plasmonic crystal that can produce a wide plasmonic bandgap near the visible frequency range. By applying a periodic zigzag structure to a metal-insulator-metal plasmonic waveguide, the lowest three plasmonic crystal bands are flattened, creating a high-quality broadband plasmonic mirror over a wavelength range of 526-909 nm. Utilizing zigzag plasmonic crystals in a three-dimensional tapered metal-insulator-metal plasmonic cavity, extreme field confinement with a modal volume of less than 0.00005 λ 3 can be achieved even at resonances over a wide frequency range. In addition, by selecting the number of zigzag periods in the plasmonic crystal, critical coupling between the cavity and the waveguide can be achieved, thereby maximizing the field intensity with an enhancement factor of 105 or more. We believe that zigzag plasmonic crystals will provide a powerful platform for implementing broadband on-chip plasmonic devices.

Near-field transmission matrix microscopy for mapping high-order eigenmodes of subwavelength nanostructures.

As nanoscale photonic devices are densely integrated, multiple near-field optical eigenmodes take part in their functionalization. Inevitably, these eigenmodes are highly multiplexed in their spectra and superposed in their spatial distributions, making it extremely difficult for conventional near-field scanning optical microscopy (NSOM) to address individual eigenmodes. Here, we develop a near-field transmission matrix microscopy for mapping the high-order eigenmodes of nanostructures, which are invisible with conventional NSOM. At an excitation wavelength where multiple modes are superposed, we measure the near-field amplitude and phase maps for various far-field illumination angles, from which we construct a fully phase-referenced far- to near-field transmission matrix. By performing the singular value decomposition, we extract orthogonal near-field eigenmodes such as anti-symmetric mode and quadruple mode of multiple nano-slits whose gap size (50 nm) is smaller than the probe aperture (150 nm). Analytic model and numerical mode analysis validated the experimentally observed modes.

Nanolayer-embedded pseudo-photonic crystals.

In recent years, novel high-performance nanophotonic devices have been realized by applying ultrathin two-dimensional nanolayer materials to nanophotonics. In this paper, we propose nanolayer-embedded compact pseudo-photonic crystals (PPCs) that enable strong interaction between ultrathin nanolayers and photonic crystal modes. In typical two-dimensional slab photonic crystals, the transverse-magnetic (TM) photonic crystal bandgap is not well formed, making it difficult to operate the TM photonic crystal waveguide modes. However, by utilizing the low-frequency TM PPC bands, a long propagation TM waveguide mode, a slow TM waveguide mode, and a TM photonic bandgap are all readily available. In particular, the insertion of a nanometer-thick low-refractive-index layer in the vertical center of TM PPC waveguide can localize the electric fields tightly in nanometer space, causing strong field interaction with the inserted nanolayer material. Using the TM slow light near PPC band edges, field interaction with the nanolayer is significantly enhanced. We can also realize nanolayer-embedded high-quality-factor (Q-factor > 104) PPC cavities using the TM PPC bandgap. We believe that the proposed TM PPCs will play an important role in the strong interaction of ultrathin nanolayer materials with photonic crystal modes.

Factors for modifying the termination of resuscitation rule in out-of-hospital cardiac arrest.

BACKGROUND: False positive rate (FPR) of the current basic life support (BLS) termination of resuscitation (TOR) rule in out-of-hospital cardiac arrest (OHCA) patients (not witnessed; no return of spontaneous circulation prior to transport; and no shocks were delivered) has been ethically challenging. We validated the current BLS TOR rule with using nationwide Korean Cardiac Arrest Research Consortium (KoCARC) registry and identified the factors for modifying the rules. METHODS: This prospective, multicenter, registry-based study was performed using the nontraumatic OHCA registry data between October 2015 and June 2017. Independent factors associated with poor neurologic outcome were identified to propose new KoCARC TOR rules by using multivariable analysis. The diagnostic performances of the TOR rules were calculated respectively. RESULTS: Among 4,360 OHCA patients, 2,801 (64.2%) satisfied all 3 criteria of the BLS TOR rule. The FPR and positive predictive value of the BLS TOR rule were 5.9% and 99.3%. Asystole as initial rhythm and age > 60 years were found as new factors for modifying the TOR rule. New KoCARC TOR rules, combination of asystole and age > 60 years with current TOR rule, showed lower FPR (0.3%-2.1%) and higher positive predictive value (99.7%-99.9%) for predicting poor neurologic outcome at discharge. CONCLUSIONS: In this recent nationwide cohort, the current BLS TOR rule showed high FPR (5.9%) for predicting poor neurologic outcome. We anticipate that our new KoCARC TOR rules, application of 2 new factors (asystole as initial rhythm and age > 60 years) with BLS TOR rule, could reduce unwarranted death.

Parapheromones Suppress Chemotherapy Side Effects.

The cytotoxic drugs used in chemotherapy are often accompanied by nausea and vomiting. Despite the use of antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) remain significant side effects for cancer patients and are associated with serotonin type 3 receptor (5-HT3R) activation in the brainstem. Farnesol and nerolidol are sesquiterpene alcohols found in essential oils of plants such as roses, citronella, and lemon grass and are used as antiemetic parapheromones. Medicinal plants often are effective in treating gastrointestinal disorders, including CINV, although the mechanism of action remains unclear. In the current work, the antiemetic efficacy of the naturally occurring racemic mixture of farnesol (m-farnesol) and nerolidol (m-nerolidol) against cisplatin CINV was tested using the pica behavior (consumption of nonnutritive substances) of rats. Animals treated with m-farnesol or m-nerolidol consumed a smaller amount of kaolin than of saline-treated control animals. This result is consistent with the antiemetic efficacy of farnesol and nerolidol. Compared with controls, m-farnesol- but not m-nerolidol-treated animals consumed more food and lost less body weight. Thus, farnesol effectively reduced appetite suppression and weight loss induced by cisplatin. In separate experiments, isomers of farnesol and nerolidol were tested on 5-HT-induced responses of acutely isolated nodose neurons using patch-clamp methods. All the tested constituents inhibited 5-HT3R-mediated current in a noncompetitive manner. Thus, both farnesol and nerolidol may exert antiemetic efficacy by inhibiting 5-HT signaling in cranial visceral afferents, resulting in interruption of emetogenic signaling; however, nerolidol failed to suppress cisplatin-induced anorexia and weight loss, suggesting that additional mechanisms may contribute.

Allopregnanolone Effects on Transmission in the Brain Stem Solitary Tract Nucleus (NTS).

During pregnancy, the progesterone metabolite, allopregnanolone (ALLO), becomes elevated and has been associated with altered levels within the CNS and resulting changes in GABAA receptor function. Pregnant animals poorly compensate reflexes for a decrease in blood pressure during hemorrhage. Previous works suggested that ALLO decreases baroreflex responses by central actions, however, the underlying mechanisms are poorly understood. In this study, we tested ALLO actions on visceral afferent synaptic transmission at second-order neurons within medial portions of the nucleus tractus solitarius (NTS) using hindbrain slices from non-pregnant female rats. Solitary tract (ST) stimulation-evoked excitatory postsynaptic currents (ST-eEPSCs) in NTS neurons directly connected to vagal afferents within the ST. ST-eEPSCs were functionally identified as monosynaptic by the latency characteristics (low jitter = standard deviation of latency, ≤200 µs) to ST stimulation. Such second-order neurons all displayed spontaneous inhibitory postsynaptic currents (sIPSCs), and low micromolar concentrations of ALLO increased frequency and decay time. At submicromolar concentrations, ALLO induced a tonic, GABAergic inhibitory current and suppressed ST-eEPSCs' amplitude. While GABAA receptor antagonist, bicuculline, blocked all ALLO effects, gabazine only blocked sIPSC actions. In current-clamp mode, ALLO perfusion increased failure of ST stimulation to trigger action potentials in most neurons. Thus, our results indicate that ALLO acts to suppress visceral afferent ST synaptic transmission at first synapses by activating pharmacologically distinct GABAA subtypes at different concentration ranges. This ALLO-mediated attenuated visceral afferent signal integration in NTS may underlie reflex changes in blood pressure during gestation.

GAREM1 regulates the PR interval on electrocardiograms.

PR interval is the period from the onset of P wave to the start of the QRS complex on electrocardiograms. A recent genomewide association study (GWAS) suggested that GAREM1 was linked to the PR interval on electrocardiograms. This study was designed to validate this correlation using additional subjects and examined the function of Garem1 in a mouse model. We analyzed the association of rs17744182, a variant in the GAREM1 locus, with the PR interval in 5646 subjects who were recruited from 2 Korean replication sets, Yangpyeong (n = 2471) and Yonsei (n = 3175), and noted a significant genomewide association by meta-analysis (P = 2.39 × 10-8). To confirm the function of Garem1 in mice, Garem1 siRNA was injected into mouse tail veins to reduce the expression of Garem1. Garem1 transcript levels declined by 53% in the atrium of the heart (P = 0.029), and Garem1-siRNA injected mice experienced a significant decrease in PR interval (43.27 ms vs. 44.89 ms in control, P = 0.007). We analyzed the expression pattern of Garem1 in the heart by immunohistology and observed specific expression of Garem1 in intracardiac ganglia. Garem1 was expressed in most neurons of the ganglion, including cholinergic and adrenergic cells. We have provided evidence that GAREM1 is involved in the PR interval of ECGs. These findings increase our understanding of the regulatory signals of heart rhythm through intracardiac ganglia of the autonomic nervous system and can be used to guide the development of a therapeutic target for heart conditions, such as atrial fibrillation.

A novel neurological function of rice bran: a standardized rice bran supplement promotes non-rapid eye movement sleep in mice through histamine H1 receptors.

SCOPE: Although rice bran has been shown to be associated with a wide spectrum of health benefits, to date, there are no reports on its effects on sleep. We investigated the effect of rice bran on sleep and the mechanism underlying this effect. METHODS AND RESULTS: Electroencephalography was used to evaluate the effects of standardized rice bran supplement (RBS) and doxepin hydrochloride (DH), a histamine H1 receptor (H1 R) antagonist used as a positive control, on sleep in mice. The mechanism of RBS action was investigated using knockout (KO) mice and ex vivo electrophysiological recordings. Oral administration of RBS and DH significantly decreased sleep latency and increased the amount of non-rapid eye movement sleep (NREMS) in mice. Similar to DH, RBS fully inhibited H1 R agonist-induced increase in action potential frequency in tuberomammillary nucleus neurons. In H1 R KO mice, neither RBS nor DH administration led to the increase in NREMS and decrease in sleep latency observed in WT mice. These results indicate that the sleep-promoting effect of RBS is completely dependent on H1 R antagonism. CONCLUSIONS: RBS decreases sleep latency and promotes NREMS through the inhibition of H1 R, suggesting that it could be a promising therapeutic agent for insomnia.

Extreme field enhancement in nano-gap plasmonic cavity via 90% efficient coupling with silicon waveguide.

We propose a novel design for a sub-5-nm-gap plasmonic cavity to couple it efficiently with an integrated low loss silicon waveguide. We numerically obtain over 90% efficient coupling between a nano-gap plasmonic cavity with a modal volume of less than 10-7λ3 and a conventional silicon-on-insulator (SOI) waveguide by utilizing the anti-symmetric second-order resonance mode of the cavity and engineering its geometry to reduce the modal size to less than 5 nm. The electromagnetic field efficiently coupled to the small cavity, leading to extreme enhancement of the field intensity. For a 2-nm-gap cavity, the intensity enhancement was calculated to be more than 100,000,000 compared to that of light in an SOI waveguide.

Comprehensive chemical profiling of Pinellia species tuber and processed Pinellia tuber by gas chromatography-mass spectrometry and liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

A comprehensive profiling method was established for the determination of various chemicals in Pinellia (P.) ternata and pedatisecta species. The profiling method comprises a fast ultrasonic extraction with various solvents, followed by GC-MS and LC-APCI-MS analysis. A total of 73 polar components as trimethylsilyl (TMS) derivatives were detected in methanol extract by GC-MS. The main components of the P. species were profiled as several kinds of fatty acids, amino acids, nucleic acids, carbohydrates, and phenolic compounds. The hexane extract was analyzed by LC-APCI-MS for the lipid profiling. A total of 35 lipid constituents [fatty acids and their esters, mono-, di-, and tri-acylglycerols] and four phytosterols were observed and tentatively characterized by LC-APCI-MS/MS. Among the phytochemicals detected in the hexane extract, triacylglycerols (TAGs) as the major component were identified by LC-APCI-MS and MS/MS. Based on the identified components, a significant difference in the chemical compositions of P. species tuber and processed P. ternata was found that the complete disappearance of TAGs and a considerable decrement of sucrose were observed in processed P. ternata. Furthermore, the degradation mechanism for TAGs in the presence of alum solution is suggested to occur during the processing P. ternata. Malic acid was found to be a characteristic compound for the classification of P. ternata and pedatisecta with different geographic origins. Based on the validated GC/MS method, twenty-four P. ternata, processed P. ternata and P. pedatisecta samples were profiled to measure the overall abundance of specific groups of compound and to identify diagnostic compounds. In addition, principal component analysis (PCA) on the GC/MS profiling data revealed a clear classification of P. species samples. In this study, the full chemical complement was for the first time reported for quality evaluation of P. species. The method can be usefully applied for phytochemical analysis of related herbal medicines.

Diagnostic performance of initial serum lactate for predicting bacteremia in female patients with acute pyelonephritis.

OBJECTIVES: The purpose of the present study was to investigate the diagnostic value of lactate for predicting bacteremia in female patients with acute pyelonephritis (APN). METHODS: We conducted a retrospective study of female patients with APN who visited the study hospital emergency department. The demographics, comorbidities, physiologies, and laboratory variables including white blood cell count and segmented neutrophil count, C-reactive protein, and initial serum lactate levels were collected and analyzed to identify associations with the presence of bacteremia. RESULTS: During the study period, a total of 314 patients were enrolled. One hundred twenty-three patients (39.2%) had bacteremia. Escherichia coli was the most frequent pathogen. Logistic regression analysis demonstrated that the lactate level was independently associated with the presence of bacteremia (odds ratio, 1.39 [95% confidence interval, 1.08-1.78]). The C-statistic of the lactate level was 0.67 (95% CI, 0.60-0.73). At a cutoff value of 1.4mmol/L, the lactate level predicted bacteremia with a sensitivity (53.7%), specificity (72.3%), positive predictive value (55.5%), negative predictive value (70.8%), positive likelihood ratio (1.93), and negative likelihood ratio (0.64). CONCLUSION: The initial serum lactate level showed poor discriminative performance for predicting bacteremia in female patients with APN.