Neuropeptide S Displays as a Key Neuromodulator in Olfactory Spatial Memory.

Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, intracerebroventricular) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, intraperitoneal) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the 2 odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons, which were densely distributed in the anterior olfactory nucleus, piriform cortex, subiculum, presubiculum, and parasubiculum. These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.

Inactivation of the Tuberomammillary Nucleus by GABAA Receptor Agonist Promotes Slow Wave Sleep in Freely Moving Rats and Histamine-Treated Rats.

A prominent hypothesis, the "flip-flop switch" model, predicts that histaminergic (HAergic) neurons in the tuberomammillary nucleus (TMN), an important component of the ascending arousal system, are inactivated by GABA mainly from the ventrolateral preoptic nucleus to allow the appearance and maintenance of sleep. However, which sleep state and the band of EEG activity induced by GABAergic inactivation of the TMN are unclear. In this study, alterations of sleep-wake states and cortical EEG power spectral density were investigated following muscimol, a GABAA-receptor agonist, microinjected bilaterally into the TMN in freely moving rats and HA pretreated rats, respectively. Muscimol dosed at 0.25 and 0.50 µg/side into the TMN during dark period dose-dependently increased slow wave sleep (SWS) accompanied by an increase in cortical EEG delta (0.5-4 Hz) and spindle (8.2-12 Hz) activities. In the meanwhile, wakefulness and EEG beta (12.2-30 Hz) activity were decreased significantly, while paradoxical sleep and EEG theta (4.2-8 Hz) activity were not changed. The increase of muscimol-induced SWS was because of prolonged SWS bout duration and not to an increased bout number. Muscimol (0.50 µg/side) administration 2 h after HA (0.125 µg/side) treatment during light period reversed the HA-induced wakefulness and EEG beta 2 (20.2-30 Hz) activity into SWS and EEG delta activity. These results demonstrate that the GABAergic inactivation of the TMN in freely moving rats and HA-treated rats promotes SWS and slow activity of cortical EEG, suggesting that the potential function of the GABAA receptor in the TMN is to dampen vigilant arousal.

Cheese Whey Protein and Blueberry Juice Mixed Fermentation Enhance the Freeze-Resistance of Lactic Acid Bacteria in the Freeze-Drying Process.

The effects of MRS, whey protein and blueberry alone, and mixed fermentation on the survival rate of lactic acid bacteria under various freeze-drying conditions were investigated. The surface structure of the freeze-dried powders was also investigated to explore the anti-freezing protection mechanism of mixed whey protein and blueberry fermentation on the bacteria. It was found that the mixed fermentation medium of blueberry and whey protein has a protective effect on the freeze-drying bacteria and is better than the traditional MRS and whey protein medium. The optimal concentration of blueberry juice addition was 9%. The survival rate of the pre-freezing temperature at -80 °C was higher than at -20 °C after the pre-freezing and freeze-drying processes. The freeze-drying thickness of 0.3 cm could improve the survival rate of the bacteria. The Fourier transform infrared spectroscopy results indicated the interaction between the whey protein, anthocyanins, and the surface composition of the lactic acid bacteria.

A novel dual polarization multiplexing RoF system integrating optical fiber and FSO channel with AMI downlink signals.

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

A novel transform domain processing based channel estimation method for OFDM radio-over-fiber systems.

In this paper, a transform domain processing (TDP) based channel estimation method for orthogonal frequency-division multiplexing (OFDM) Radio-over-Fiber (RoF) systems is proposed. Theoretically investigation shows that TDP can greatly reduce the number of required training symbols. An 8 x 4.65 Gb/s multi-user OFDM RoF system over 40 km fiber link and 60 GHz wireless link is experimentally demonstrated utilizing TDP scheme. Compared with conventional time domain averaging (TDA) scheme, the overhead can be reduced from several tens of training symbols to merely one symbol and the receiver sensitivity has been improved by 1.8 dB at BER of 3.8 x 10(-3). The calculated BER performance for 8 wireless users clearly validates the feasibility of this TDP-based channel estimation method.

Flattened comb generation using only phase modulators driven by fundamental frequency sinusoidal sources with small frequency offset.

We propose and experimentally demonstrate a simple scheme to generate flattened optical subcarriers at low insertion loss using only phase modulators driven by fundamental frequency sinusoidal sources. A small frequency offset is introduced in the second stage to obtain phase-insensitive, stable, and flattened subcarriers. Theoretical and numerical analysis with experimental results are carried out on this scheme. Twenty-one stable comb tones with 25 GHz frequency spacing are obtained with power difference less than 3 dB. The good bit-error-ratio performance of 160.8 Gb/s polarization-division-multiplexing quadrature-phase-shift-keying signal carried by one selected subcarrier clearly demonstrates the feasibility of this comb generation scheme.

A novel odor stimulation system in freely moving, behaving animals.

Precise and reliable presentation of odorants to animals is crucial for olfactory studies. Although odor stimulation systems in anesthetized or awake, head-fixed animals are well established, temporally precise odor presentation in awake, freely moving animals remains a challenge. Here, we describe a new odor stimulation system which presents odors directly to the nostrils of freely moving mice. The system comprises 3 modules: an odor-delivery module, an odor-generation module, and a control module. The new system is precise and temporally reliable, and odor stimulation can be triggered by specific sniffing phases or other events. Moreover, the system can be combined with neural recordings, such as electrophysiology, and olfactory behavioral tests to investigate how neurons in the brain represent odor information during individual olfactory behaviors. This innovative odor stimulation system may replace traditional stimulation systems: It will enable precise odor presentation in a wide range of olfactory studies in freely moving animals.

The Ponto-Geniculo-Occipital (PGO) Waves in Dreaming: An Overview.

Rapid eye movement (REM) sleep is the main sleep correlate of dreaming. Ponto-geniculo-occipital (PGO) waves are a signature of REM sleep. They represent the physiological mechanism of REM sleep that specifically limits the processing of external information. PGO waves look just like a message sent from the pons to the lateral geniculate nucleus of the visual thalamus, the occipital cortex, and other areas of the brain. The dedicated visual pathway of PGO waves can be interpreted by the brain as visual information, leading to the visual hallucinosis of dreams. PGO waves are considered to be both a reflection of REM sleep brain activity and causal to dreams due to their stimulation of the cortex. In this review, we summarize the role of PGO waves in potential neural circuits of two major theories, i.e., (1) dreams are generated by the activation of neural activity in the brainstem; (2) PGO waves signaling to the cortex. In addition, the potential physiological functions during REM sleep dreams, such as memory consolidation, unlearning, and brain development and plasticity and mood regulation, are discussed. It is hoped that our review will support and encourage research into the phenomenon of human PGO waves and their possible functions in dreaming.

An α-hemoglobin-derived peptide (m)VD-hemopressin (α) promotes NREM sleep via the CB1 cannabinoid receptor.

Hemopressin and related peptides have shown to function as the endogenous ligands or the regulator of cannabinoid receptors. The previous studies demonstrated that the endocannabinoid system played important roles in modulating several physiological functions such as sleep, olfaction, emotion, learning and memory, and reward behaviors. Mouse VD-hemopressin (α) [(m)VD-HPα], an 11-residue peptide derived from the α1 chain of hemoglobin, was recently presumed as a selective agonist of the CB1 receptor. The present study was undertaken to investigate the effects of (m)VD-HPα on the sleep-wake cycle and power spectrum of cortical EEG in freely moving rats and the potential neurons in the brain activated by (m)VD-HPα. The results showed that 20.1 nmol of (m)VD-HPα i.c.v. administration increased non-rapid eye movement (NREM) sleep in the first 2 h section accompanied by an increase in EEG delta (0.5-4 Hz) activity. The (m)VD-HPα-induced NREM sleep enhancement was due to extended episode duration instead of the episode number. In addition, the effect of (m)VD-HPα (20.1 nmol) on sleep-wake states was significantly attenuated by an antagonist of the CB1 receptor, AM251 (20 nmol, i.c.v.) but not by the CB2 receptor antagonist, AM630 (20 nmol, i.c.v.). In comparison with vehicle, (m)VD-HPα increased Fos-immunoreactive (-ir) neurons in the ventrolateral preoptic nucleus (VLPO), but reduced Fos-ir neurons in the lateral hypothalamus (LH), tuberomammillary nucleus (TMN), and locus coeruleus (LC). These findings suggest that (m)VD-HPα promotes NREM sleep via the CB1 cannabinoid receptor to probably activate VLPO GABAergic neurons, but inactivates the LH orexinergic, LC noradrenergic, and TMN histaminergic neurons.

MicroRNA-218 instructs proper assembly of hippocampal networks.

The assembly of the mammalian brain is orchestrated by temporally coordinated waves of gene expression. Post-transcriptional regulation by microRNAs (miRNAs) is a key aspect of this program. Indeed, deletion of neuron-enriched miRNAs induces strong developmental phenotypes, and miRNA levels are altered in patients with neurodevelopmental disorders. However, the mechanisms used by miRNAs to instruct brain development remain largely unexplored. Here, we identified miR-218 as a critical regulator of hippocampal assembly. MiR-218 is highly expressed in the hippocampus and enriched in both excitatory principal neurons (PNs) and GABAergic inhibitory interneurons (INs). Early life inhibition of miR-218 results in an adult brain with a predisposition to seizures. Changes in gene expression in the absence of miR-218 suggest that network assembly is impaired. Indeed, we find that miR-218 inhibition results in the disruption of early depolarizing GABAergic signaling, structural defects in dendritic spines, and altered intrinsic membrane excitability. Conditional knockout of Mir218-2 in INs, but not PNs, is sufficient to recapitulate long-term instability. Finally, de-repressing Kif21b and Syt13, two miR-218 targets, phenocopies the effects on early synchronous network activity induced by miR-218 inhibition. Taken together, the data suggest that miR-218 orchestrates formative events in PNs and INs to produce stable networks.

Spectrally efficient localized carrier distribution scheme for multiple-user DFT-S OFDM RoF- PON wireless access systems.

We propose a modified localized carrier distribution scheme based on multi-tone generation to generate 60 GHz mm-wave for different wireless users and it improves the carrier utilization efficiency by 33.3%. The principle of multiple-user discrete Fourier transform spread optical orthogonal frequency-division multiplexing (DFT-S OFDM) Radio-over-fiber (RoF) system is presented. This multiple-user system is applicable to passive optical network (PON). Then we demonstrate a 8 x 4.65 Gb/s multiple-user DFT-S OFDM RoF-PON wireless access system over 40 km fiber link and 60 GHz wireless link using two localized carrier distribution scheme with different spectral efficiency. Compared to conventional OFDM, 2.3 dB reduction of receiver power using DFT-S OFDM modulation scheme and the calculated BER performance for 8 wireless users clearly demonstrates the feasibility of this spectrally efficient multiple-user RoF-PON scheme.

Seamless integration of 57.2-Gb/s signal wireline transmission and 100-GHz wireless delivery.

We experimentally demonstrated the seamless integration of 57.2-Gb/s signal wireline transmission and 100-GHz wireless delivery adopting polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) modulation with 400-km single-mode fiber-28 (SMF-28) transmission and 1-m wireless delivery. The X- and Y-polarization components of optical PDM-QPSK baseband signal are simultaneously up-converted to 100 GHz by optical polarization-diversity heterodyne beating, and then independently transmitted and received by two pairs of transmitter and receiver antennas, which make up a 2x2 multiple-input multiple-output (MIMO) wireless link based on microwave polarization multiplexing. At the wireless receiver, a two-stage down conversion is firstly done in analog domain based on balanced mixer and sinusoidal radio frequency (RF) signal, and then in digital domain based on digital signal processing (DSP). Polarization de-multiplexing is realized by constant modulus algorithm (CMA) based on DSP in heterodyne coherent detection. Our experimental results show that more taps are required for CMA when the X- and Y-polarization antennas have different wireless distance.

Multi-channel multi-carrier generation using multi-wavelength frequency shifting recirculating loop.

We propose and experimentally demonstrate a novel scheme to generate optical frequency-locked multi-channel multi-carriers (MCMC), using a recirculating frequency shifter (RFS) loop based on multi-wavelength frequency shifting single side band (MWFS-SSB) modulation. In this scheme, optical subcarriers with multiple wavelengths can be generated each round. Furthermore, the generated MCMC are frequency- and phase-locked within each channel, and therefore can be effectively used for WDM superchannel. Dual-wavelength frequency shifting SSB modulation is carried out with dual-wavelength optical seed source in our experimental demonstration. Using this scheme, we successfully generate dual-channel multi-carriers, and one channel has 28 subcarriers while the other has 29 ones with 25-GHz subcarrier spacing. We also experimentally demonstrate that this kind of source can be used to carry 50-Gb/s optical polarization-division-multiplexing quadrature phase shift keying (PDM-QPSK) signal.

Fiber-wireless transmission system of 108 Gb/sdata over 80 km fiber and 2×2multiple-input multiple-output wireless links at 100 GHz W-band frequency.

We experimentally demonstrate a seamlessly integrated fiber-wireless system that delivers a 108 Gb/s signal through 80 km fiber and 1 m wireless transport over free space at 100 GHz adopting polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) modulation and heterodyning coherent detection. The X- and Y-polarization components of the optical PDM-QPSK baseband signal are simultaneously upconverted to 100 GHz wireless carrier by optical polarization-diversity heterodyne beating, and then independently transmitted and received by two pairs of transmitter and receiver antennas, which form a 2×2 multiple-input multiple-output wireless link. At the wireless receiver, two-stage downconversion is performed firstly in the analog domain based on balanced mixer and sinusoidal radio frequency signal, and then in the digital domain based on digital signal processing (DSP). Polarization demultiplexing is realized by the constant modulus algorithm in the DSP part at the receiver. The bit-error ratio for the 108 Gb/s PDM-QPSK signal is less than the pre-forward-error-correction threshold of 3.8×10(-3) after both 1 m wireless delivery at 100 GHz and 80 km single-mode fiber-28 transmission. To our knowledge, this is the first demonstration to realize 100 Gb/s signal delivery through both fiber and wireless links at 100 GHz.

Multichannel optical frequency-locked multicarrier source generation based on multichannel recirculation frequency shifter loop.

We propose and experimentally demonstrate a novel scheme to generate multichannel optical frequency-locked multicarrier by using multichannel recirculating frequency shifter (MC-RFS) loop. By using MC-RFS loop, we can generate N channels subcarriers each round trip without interference. These subcarriers of each channel are stable and frequency-locked, which can be used for a multichannel WDM source. Finally, the double channels RFS loop is carried out for demonstration in our experiment with double-carriers source. Using this scheme, we successfully generate 54 frequency-locked subcarriers with 25 GHz frequency spacing in two channels and each channel has 27 tones.

Simplified coherent receiver with heterodyne detection of eight-channel 50 Gb/s PDM-QPSK WDM signal after 1040 km SMF-28 transmission.

We propose and experimentally demonstrate a simplified coherent receiver based on heterodyne detection with only two balanced photodetectors and two analog-to-digital converters. The polarization diversity hybrid can be simplified relative to the conventional one. The detected intermediate frequency signals are first downconverted to baseband with inphase and quadrature separation. Using this scheme, we successfully demonstrated the eight-channel 50 Gb/s polarization division multiplexed quadrature phase shift keying WDM signal with heterodyne detection based on digital signal processing over 1040 km single-mode fiber 28 with erbium-doped fiber amplifier only amplification.

Upregulation of EMID1 Accelerates to a Favorable Prognosis and Immune Infiltration in Lung Adenocarcinoma.

Lung cancer is a difficult-to-treat cancer. Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. Although there are many ways to treat lung cancer, the survival rate of patients is low. Therefore, novel molecules need to be identified to diagnose and treat LUAD. This study utilized The Cancer Genome Atlas (TCGA) LUAD data to analyze and validate the value of EMID1 as a LUAD diagnostic surface marker and overall survival prognostic marker. Differential expression analysis formally confirmed that decreased EMID1 expression was significantly associated with advanced stage and metastasis of lung cancer. Kaplan-Meier survival analysis showed that the patients with low EMID expression are dismal. The relationship between clinicopathological features and EMID1 was scored using Wilcoxon signed-rank test and R (v.3.5.1) logistic regression and suggested that patients with low EMID1 expression had a worse prognosis than patients with high EMID1 expression. (Gene Ontology) GO, Kyoto Encyclopedia of Genes and Genomes(KEGG), and gene set enrichment analysis (GSEA) were performed to investigate the potential mechanism of EMID1 expression on the prognosis of LUAD and suggested that Notch signaling pathway may be an important biological pathway for EMID1 to play a role in LUAD. Further, combined with univariate and multivariate Cox regression analysis, it was speculated that high and low levels of EMID1 expression and the logistic regression analysis of related clinical variables had significant clinical significance to verify the underlying mechanism of LUAD focus and prognosis. EMID1 plays an important role in the immune milieu of LUAD. Meanwhile, the correlation between tumor-infiltrating immune cells and genes was assessed using CIBERSORT, and it was found that the level of B cell infiltration was positively correlated with the expression of EMID1, all of which were validated in the GEO and GEPIA databases. In all, this study helps to understand the immune microenvironment of LUAD and improve the survival of patients with LUAD. Thus, EMID1 may be a novel immune-related prognostic marker of LUAD.

Stereotaxic atlas of the infant rat brain at postnatal days 7-13.

Recently, researchers have paid progressively more attention to the study of neural development in infant rats. However, due to the lack of complete intracerebral localization information, such as clear nuclear cluster boundaries, identified main brain structures, and reliable stereotaxic coordinates, it is difficult and restricted to apply technical neuroscience to infant rat's brain. The present study was undertaken to refine the atlas of infant rats. As such, we established a stereotaxic atlas of the infant rat's brain at postnatal days 7-13. Furthermore, dye calibration surgery was performed in P7-P13 infant rats by injecting Methylene blue, and sections were incubated in Nissl solutions. From the panoramic images of the brain sections, atlases were made. Our article has provided the appearance and measurements of P7-P13 Sprague-Dawley rat pups. Whereas the atlas contains a series of about 530 coronal brain section images from olfactory bulbs to the brainstem, a list of abbreviations of the main brain structures, and reliable stereotaxic coordinates, which were demonstrated by vertical and oblique injections with fluorescent dye DiI. The present findings demonstrated that our study of P7-P13 atlases has reasonable nucleus boundaries and accurate and good repeatability of stereotaxic coordinates, which can make up for the shortage of postnatal rat brain atlas currently in the field.

Rapid Eye Movement Sleep during Early Life: A Comprehensive Narrative Review.

The ontogenetic sleep hypothesis suggested that rapid eye movement (REM) sleep is ontogenetically primitive. Namely, REM sleep plays an imperative role in the maturation of the central nervous system. In coincidence with a rapidly developing brain during the early period of life, a remarkably large amount of REM sleep has been identified in numerous behavioral and polysomnographic studies across species. The abundant REM sleep appears to serve to optimize a cerebral state suitable for homeostasis and inherent neuronal activities favorable to brain maturation, ranging from neuronal differentiation, migration, and myelination to synaptic formation and elimination. Progressively more studies in Mammalia have provided the underlying mechanisms involved in some REM sleep-related disorders (e.g., narcolepsy, autism, attention deficit hyperactivity disorder (ADHD)). We summarize the remarkable alterations of polysomnographic, behavioral, and physiological characteristics in humans and Mammalia. Through a comprehensive review, we offer a hybrid of animal and human findings, demonstrating that early-life REM sleep disturbances constitute a common feature of many neurodevelopmental disorders. Our review may assist and promote investigations of the underlying mechanisms, functions, and neurodevelopmental diseases involved in REM sleep during early life.

Generation of full C-band coherent and frequency-lock multi-carriers by using recirculating frequency shifter loops based on phase modulator with external injection.

We demonstrate the generation of full C-band coherent and frequency-lock multi-carriers by using two recirculating frequency shifter (RFS) EDFA loops based on phase modulator with external injection-seeding. In our proposed novel scheme, only one phase modulator is used in each loop and two loops are used to generate long wavelength and short wavelength subcarriers, respectively. Full C-band with totally 178 subcarriers and 26 GHz subcarrier frequency spacing covering nearly 36.66 nm from 1527.54 to 1564.20 nm are obtained. The performance of 178 subcarriers with superior flatness less than 3dB and tone-to-noise ratio (TNR) larger than 20 dB after a wavelength selective switch (WSS) shows that this novel scheme is a potential technique for the future 10Tb/s optical communication.