Paeonol and glycyrrhizic acid in combination ameliorate the recurrent nitroglycerin-induced migraine-like phenotype in rats by regulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonol (PAE) and glycyrrhizic acid (GLY) are predominate components of 14 blood-entering ones of Piantongtang No. 1, which is a traditional Chinese medicine prescription for chronic migraine with minimal side effects. Both paeonol and glycyrrhizic acid exhibit analgesic, neuroprotective and anti-inflammatory properties individually. Our previous research has highlighted their combined effect (PAE + GLY) in ameliorating migraine symptoms. However, there are not yet any studies exploring the mechanism of action of PAE + GLY in the treatment of migraine. AIM OF THE STUDY: This research aimed to determine the mechanism of PAE + GLY in ameliorating the recurrent nitroglycerin-induced migraine-like phenotype in rats. MATERIALS AND METHODS: Using a nitroglycerin-induced migraine model via subcutaneous injection in the neck, we evaluated the effect of PAE + GLY on migraine-like symptoms. Behavioural tests and biomarkers analysis were employed, alongside transcriptome sequencing (RNA-seq). Mechanistic insights were further verified utilising reverse transcription quantitative PCR (RT-qPCR), Western blot (WB), ELISA and immunofluorescence (IF) techniques. RESULTS: Following treatment with PAE + GLY, hyperalgesia threshold and 5-hydroxytryptamine (5-HT) levels increased, and migraine-like head scratching, histamine and calcitonin gene-related peptide (CGRP) levels were reduced. RNA-Seq experiments revealed that PAE + GLY upregulated the expression of Glutamate decarboxylase 2 (GAD2) and γ-aminobutyric acid type B receptor subunit 2 (GABBR2) genes. This upregulation activated the GABAergic synapse pathway, effectively inhibiting migraine attacks. Further validation demonstrated an increase in γ-aminobutyric acid (GABA) content in cerebrospinal fluid post PAE + GLY treatment, coupled with increased expression of dural GAD2, GABBR2 and transient receptor potential channel M8 (TRPM8). Consequently, this inhibited the expression of dural cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and transient receptor potential channel type 1 (TRPV1), subsequently downregulating p-ERK1/2, p-AKT1, IL-1ß and TNF-α. CONCLUSIONS: Our findings underscore that PAE + GLY ameliorates inflammatory hyperalgesia migraine by upregulating inhibitory neurotransmitters and modulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

Current Advances in the Functional Diversity and Mechanisms Underlying Endophyte-Plant Interactions.

Plant phenotype is a complex entity largely controlled by the genotype and various environmental factors. Importantly, co-evolution has allowed plants to coexist with the biotic factors in their surroundings. Recently, plant endophytes as an external plant phenotype, forming part of the complex plethora of the plant microbial assemblage, have gained immense attention from plant scientists. Functionally, endophytes impact the plant in many ways, including increasing nutrient availability, enhancing the ability of plants to cope with both abiotic and biotic stress, and enhancing the accumulation of important plant secondary metabolites. The current state of research has been devoted to evaluating the phenotypic impacts of endophytes on host plants, including their direct influence on plant metabolite accumulation and stress response. However, there is a knowledge gap in how genetic factors influence the interaction of endophytes with host plants, pathogens, and other plant microbial communities, eventually controlling the extended microbial plant phenotype. This review will summarize how host genetic factors can impact the abundance and functional diversity of the endophytic microbial community, how endophytes influence host gene expression, and the host-endophyte-pathogen disease triangle. This information will provide novel insights into how breeders could specifically target the plant-endophyte extended phenotype for crop improvement.

BTCRSleep: a boundary temporal context refinement-based fully convolutional network for sleep staging with single-channel EEG.

Objective. Sleep staging studies on single-channel EEG mainly exploit deep learning methods that combine convolutional neural networks (CNNs) and recurrent neural networks. However, when typical brain waves (such as K-complexes or sleep spindles) that identify sleep stages span two epochs, the abstract process of a CNN extracting features from each sleep stage may cause the loss of boundary context information. This study attempts to capture the boundary context, which contains the characteristics of brain waves during sleep stage transition, to improve the performance of sleep staging.Approach. In this paper we propose a fully convolutional network with boundary temporal context refinement, called BTCRSleep (Boundary Temporal Context Refinement Sleep). The boundary temporal context refinement module refines the boundary information on sleep stages on the basis of extracting multi-scale temporal dependences between epochs and enhances the abstract capability of the boundary temporal context. In addition, we design a class-aware data augmentation method to effectively learn the boundary temporal context between the minority class and other sleep stages.Main results. We evaluate the performance of our proposed network using four public datasets: the 2013 version of Sleep-EDF Expanded (SEDF), the 2018 version of Sleep-EDF Expanded (SEDFX), the Sleep Heart Health Study (SHHS) and CAP Sleep Database (CAP). The evaluation results on the four datasets showed that our model obtains the best total accuracy and kappa score compared with state-of-the-art methods. On average, accuracies of 84.9% in SEDF, 82.9% in SEDFX, 85.2% in SHHS and 76.9% in CAP are obtained under subject-independent cross-validation. We demonstrate that the boundary temporal context contributes to the improvement in capturing the temporal dependences across different epochs.

Nitric Oxide Regulates Seed Germination by Integrating Multiple Signalling Pathways.

Seed germination is of great significance for plant development and crop yield. Recently, nitric oxide (NO) has been shown to not only serve as an important nitrogen source during seed development but also to participate in a variety of stress responses in plants to high salt, drought, and high temperature. In addition, NO can affect the process of seed germination by integrating multiple signaling pathways. However, due to the instability of NO gas activity, the network mechanism for its fine regulation of seed germination remains unclear. Therefore, this review aims to summarize the complex anabolic processes of NO in plants, to analyze the interaction mechanisms between NO-triggered signaling pathways and different plant hormones such as abscisic acid (ABA) and gibberellic acid (GA), ethylene (ET) and reactive oxygen species (ROS) signaling molecules, and to discuss the physiological responses and molecular mechanisms of seeds during the involvement of NO in abiotic stress, so as to provide a reference for solving the problems of seed dormancy release and improving plant stress tolerance.

The characteristics of soil microbial co-occurrence networks across a high-latitude forested wetland ecotone in China.

To understand the effect of seasonal variations on soil microbial communities in a forested wetland ecotone, here, we investigated the dynamics of the diversities and functions of both soil bacterial and fungal communities inhabiting three wetland types (forested wetland, shrub wetland and herbaceous vegetation wetland) from forest-wetland ecotone of northern Xiaoxing'an Mountains spanning different seasons. ß-diversity of soil microbial communities varied significantly among different vegetation types (Betula platyphylla-Larix gmelinii, Alnus sibirica, Betula ovalifolia, and Carex schmidtii wetlands). We totally detected 34 fungal and 14 bacterial indicator taxa among distinctive groups by using Linear discriminant analysis effect size (LEfSe) analysis, and identified nine network hubs as the most important nodes detected in whole fungi, bacteria, and fungi-bacteria networks. At the vegetation type-level, bacterial and fungal microbiome living in C. schmidtii wetland soil possessed fewer positive interactions and lower modularity than those in other types of wetland soil. Furthermore, we also discovered that ectomycorrhizal fungi were dominant in the fungal microbiota existing in forested and shrub wetland soils, whereas arbuscular mycorrhizal fungi were predominated in those residing in herbaceous vegetation wetland soil. The distribution of the predicted bacterial functional enzymes also obviously varied among different vegetation-types. In addition, the correlation analysis further revealed that the key fungal network modules were significantly affected by the contents of total N and soil water-soluble K, whereas most of the bacterial network modules were remarkably positively driven by the contents of total N, soil water-soluble K, Mg and Na. Our study suggested that vegetation type are substantive factors controlling the diversity, composition and functional group of soil microbiomes from forest-wetland ecotone of northern Xiaoxing'an Mountains.

Exogenous Ethylene Alleviates the Inhibition of Sorbus pohuashanensis Embryo Germination in a Saline-Alkali Environment (NaHCO3).

Saline-alkali stress is a major environmental stress affecting the growth and development of plants such as Sorbus pohuashanensis. Although ethylene plays a crucial role in plant response to saline-alkaline stress, its mechanism remains elusive. The mechanism of action of ethylene (ETH) may be related to the accumulation of hormones, reactive oxygen species (ROS), and reactive nitrogen species (RNS). Ethephon is the exogenous ethylene donor. Therefore, for the present study we initially used different concentrations of ethephon (ETH) to treat S. pohuashanensis embryos and identified the best treatment concentration and method to promote the release of dormancy and the germination of S. pohuashanensis embryos. We then analyzed the physiological indexes, including endogenous hormones, ROS, antioxidant components, and reactive nitrogen, in embryos and seedlings to elucidate the mechanism via which ETH manages stress. The analysis showed that 45 mg/L was the best concentration of ETH to relieve the embryo dormancy. ETH at this concentration improved the germination of S. pohuashanensis by 183.21% under saline-alkaline stress; it also improved the germination index and germination potential of the embryos. Further analysis revealed that ETH treatment increased the levels of 1-aminocyclopropane-1-carboxylic acid (ACC), gibberellin (GA), soluble protein, nitric oxide (NO), and glutathione (GSH); increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), nitrate reductase (NR), and nitric oxide synthase (NOS); and decreased the levels of abscisic acid (ABA), hydrogen peroxide (H2O2), superoxide anion, and malondialdehyde (MDA) of S. pohuashanensis under saline-alkali stress. These results indicate that ETH mitigates the inhibitory effects of saline-alkali stress and provides a theoretical basis by which to establish precise control techniques for the release of seed dormancy of tree species.

Evaluating personnel evacuation risks under fire scenario of Airbus wide-body aircraft: A simulation study.

Airliner accidents are often accompanied by incidental aircraft fires, causing huge casualties and incalculable economic losses. The research on airliner fire and its emergency evacuation is the focus and difficulty of aviation safety research, but it is difficult to carry out the research through experiments, and the use of computer simulation is an effective method. This paper comprehensively studies the dynamic development of the cabin fire and the corresponding cabin evacuation when the wide-body airliner Airbus A350-900 is forced to land in two states: horizontal and forward. The spatial distribution of the remaining evacuation time at each seat is used to analyze and judge the safety evacuation risk of the airliner cabin. Finally, two evacuation optimization design ideas based on partition guidance and seat layout are proposed to improve the spatial distribution of the overall evacuation risk of passengers in the cabin and provide some reference suggestions for strengthening fire prevention in the design, manufacture, and use of airliner. Some targeted countermeasures are put forward for the emergency evacuation of passengers in the cabin in a fire situation.

SleepContextNet: A temporal context network for automatic sleep staging based single-channel EEG.

BACKGROUND AND OBJECTIVE: Single-channel EEG is the most popular choice of sensing modality in sleep staging studies, because it widely conforms to the sleep staging guidelines. The current deep learning method using single-channel EEG signals for sleep staging mainly extracts the features of its surrounding epochs to obtain the short-term temporal context information of EEG epochs, and ignore the influence of the long-term temporal context information on sleep staging. However, the long-term context information includes sleep stage transition rules in a sleep cycle, which can further improve the performance of sleep staging. The aim of this research is to develop a temporal context network to capture the long-term context between EEG sleep stages. METHODS: In this paper, we design a sleep staging network named SleepContextNet for sleep stage sequence. SleepContextNet can extract and utilize the long-term temporal context between consecutive EEG epochs, and combine it with the short-term context. we utilize Convolutional Neural Network(CNN) layers for learning representative features from each sleep stage and the representation features sequence learned are fed into a Recurrent Neural Network(RNN) layer for learning long-term and short-term context information among sleep stage in chronological order. In addition, we design a data augmentation algorithm for EEG to retain the long-term context information without changing the number of samples. RESULTS: We evaluate the performance of our proposed network using four public datasets, the 2013 version of Sleep-EDF (SEDF), the 2018 version of Sleep-EDF Expanded (SEDFX), Sleep Heart Health Study (SHHS) and the CAP Sleep Database. The experimental results demonstrate that SleepContextNet outperforms state-of-the-art techniques in terms of different evaluation metrics by capturing long-term and short-term temporal context information. On average, accuracy of 84.8% in SEDF, 82.7% in SEDFX, 86.4% in SHHS and 78.8% in CAP are obtained under subject-independent cross validation. CONCLUSIONS: The network extracts the long-term and short-term temporal context information of sleep stages from the sequence features, which utilizes the temporal dependencies among the EEG epochs effectively and improves the accuracy of sleep stages. The sleep staging method based on forward temporal context information is suitable for real-time family sleep monitoring system.

Bioactive Compounds of Polygonatum sibiricum - Therapeutic Effect and Biological Activity.

Plants serve as an important source of medicinal compounds, and their use in various diseases dates back hundreds of years. One such plant-based compound and the discovery of the antimalarial drug, artemisinin, has significantly brought phytomedicines into the spotlight and has enhanced the understanding and, consequently, the application of formulations derived from plants. Traditional Chinese Medicine (TCM), which is based primarily on plants, holds immense potential and is an unexplored source for modern medicine. Many herbs, including Polygonatum sibiricum (PS), are used in Chinese medicine to treat various diseases. Polygonatum sibiricum (PS) belongs to the Liliaceae family and is used not only as a medicinal but also dietary supplement. PS has a highly diverse composition of bioactive compounds such as flavones, homoisoflavanone, alkaloids, lignins, steroid saponins, triterpenoid saponins, polysaccharides, etc. Because of such diverse composition, PS has been used as an anti-aging, anti-inflammatory, anti-osteoporotic agent, as well as an immunity booster, sleep enhancer, etc. Therefore, in this article, we review the therapeutic effect of bioactive compounds such as polysaccharides, saponins, and PS extract in various diseases and their biological activities in fatigue, immunity, sleep, anti-aging, etc.

Values of Contrast-Enhanced Ultrasound in Classification and Diagnosis of Common Bile Duct and Superficial Organ Lesions under Compression Algorithm.

This work aimed to investigate values of contrast-enhanced ultrasound (CEUS) under DEFLATE in the classification and diagnosis of the common bile duct and superficial lymphoid lesions. 88 patients with lower common bile duct lesions and 126 patients with superficial lymphoid lesions were selected as the subjects investigated and examined by CEUS under DEFLATE to compare characteristics and diagnostic efficiency of CEUS in different types of lesions. The time-intensity curve (TIC) was for quantitative analysis on CEUS results. The results showed that there were statistically significant differences in the comparison of time to peak (TTP), area under the curve (AUC), and gradient (Grad) of common bile duct walls in patients from the malignant group (P < 0.05), while the comparison of three indicators of patients in the benign group was not statistically remarkable (P > 0.05). In addition, there were statistically great differences in TTP, AUC, and Grad among patients in the benign and malignant groups (P < 0.05). The sensitivity, specificity, accuracy, and positive/negative predictive value of CEUS + ultrasound (US) in the diagnosis of benign and malignant lymph nodes were 92.83%, 87.14%, 89.54%, 91.23%, and 86.43%, respectively. The values of maximal intensity (I max) in the reactive hyperplasia group (group A), lymphoma group (group B), and metastatic lymph nodes group (group C) were compared, showing statistical differences (P < 0.05). The TTP and AUC of group B were higher than those of groups A and C, respectively (P < 0.05), and the base-to-peak ascending slope (K UP) and the absolute value of the semidescending slope (K DOWN) in group C increased hugely compared to group A (P < 0.05). It indicated that CEUS examination under DEFLATE could be applied in the qualitative diagnosis of lower common bile duct lesions and superficial lymphoid lesions, which was worthy of clinical application.

Characteristics and metabolic patterns of soil methanogenic archaea communities in the high-latitude natural forested wetlands of China.

Soil methanogenic microorganisms are one of the primary methane-producing microbes in wetlands. However, we still poorly understand the community characteristic and metabolic patterns of these microorganisms according to vegetation type and seasonal changes. Therefore, to better elucidate the effects of the vegetation type and seasonal factors on the methanogenic community structure and metabolic patterns, we detected the characteristics of the soil methanogenic mcrA gene from three types of natural wetlands in different seasons in the Xiaoxing'an Mountain region, China. The results indicated that the distribution of Methanobacteriaceae (hydrogenotrophic methanogens) was higher in winter, while Methanosarcinaceae and Methanosaetaceae accounted for a higher proportion in summer. Hydrogenotrophic methanogenesis was the dominant trophic pattern in each wetland. The results of principal coordinate analysis and cluster analysis showed that the vegetation type considerably influenced the methanogenic community composition. The methanogenic community structure in the Betula platyphylla-Larix gmelinii wetland was relatively different from the structure of the other two wetland types. Indicator species analysis further demonstrated that the corresponding species of indicator operational taxonomic units from the Alnus sibirica wetland and the Betula ovalifolia wetland were similar. Network analysis showed that cooperative and competitive relationships exist both within and between the same or different trophic methanogens. The core methanogens with higher abundance in each wetland were conducive to the adaptation to environmental disturbances. This information is crucial for the assessment of metabolic patterns of soil methanogenic archaea and future fluxes in the wetlands of the Xiaoxing'an Mountain region given their vulnerability.

Long-term and strong suppression against Microcystis growth and microcystin-release by luteolin continuous-release microsphere: Optimal construction, characterization, effects and proteomic mechanisms.

Microcystis-dominated cyanobacterial blooms (MCBs) severely threaten ecological health by causing hypoxia and releasing microcystins (MCs). Luteolin has potential as low-cost eco-safe algaecide against Microcystis, but to enhance sustainability of its algicidal effect and elucidate underlying mechanisms at proteomic level are urgently desirable. This study optimally constructed continuous-release microsphere (CRM) of luteolin with strong solidity and durability even after long-term immersion. Applying luteolin CRM, this study developed a long-term algicidal option to strongly inhibit Microcystis growth and MC-release until 49 days, with inhibition ratios of growth and MC-release (both ≥ 98%) and inhibitory effect-lasting time (nearly 50 days) of CRM superior to most former reports, and long-term strong inhibitory effects of CRM on Microcystis growth and MC-release kept stable at various nitrogen levels. Also, luteolin CRM rendered extracellular MCs content decrease to nearby acceptable threshold for drinking water. These signified a promising prospect of luteolin CRM in sustained effective control against toxigenic MCBs in waters of different eutrophic states. Comparative proteomic analysis showed that luteolin CRM significantly up-regulated photosynthesis and protein homestasis, but down-regulated other processes including stress response, MC-synthesis/release, glycolysis, amino acid synthesis, fatty acid synthesis/ß-oxidation, tricarboxylic acid cycle, transcription, translation, transport, cell shaping and cell division. These implied that continuous stress of luteolin released from CRM induced Microcystis proteome towards a shift of higher energy storage but lower energy release/consumption, which largely disturbed its physiological metabolic processes and thus negatively impact its growth. Proteomics results shed newly deep insights on algicidal mechanisms of flavonoid in the form of CRM.

The Possible Effects of Breastfeeding on Infant Development at 3 Months: A Case-Control Study.

Objective: To examine the influence of exclusive breastfeeding on infant development among 3-month-old infants in a Chinese population. Methods: Mothers and their 3-month-old infants were recruited from four maternal and child health hospitals from April 2018 to March 2019. Based on the infants' feeding patterns, the mother-infant dyads were divided into two groups: exclusive breastfeeding and formula feeding groups. Infant development was evaluated using the Chinese version of the Ages and Stages Questionnaires, 3rd edition (ASQ-C), and maternal depression, parenting confidence, and infant temperament were also assessed using the relevant scales/questionnaires. Multivariate logistic regression analysis was conducted to explore the effects of feeding patterns on infant development at 3 months. Results: The data from 417 mother-infant dyads were analyzed. For the breastfeeding group and formula feeding group, the risk of developmental delay measured by the ASQ-C was 4.1% (10/244) and 9.3% (16/173) respectively for the communication domain; 5.7% (14/244) and 8.1% (14/173) for problem-solving domain and 6.2% (15/244) and 12.1% (21/173) for personal-social domain, respectively. Compared with exclusive breastfeeding, formula feeding was a risk factor for delayed development of communication (adjusted odd ratio [aOR] = 2.60, 95% confidence interval [CI] = 1.42-4.75) problem-solving (aOR = 1.91, 95% CI = 1.06-3.45), and personal-social skills (aOR = 1.96, 95% CI = 1.12-3.42). Conclusions: Exclusive breastfeeding is important for infant communication, problem solving, and social interaction at the age of 3 months. Formula-fed infants may be at a higher risk of developmental delay than exclusively breast-fed infants. It is necessary to encourage mothers to establish and continuous breastfeeding.

Tumor necrosis factor ligand-related molecule 1A affects the intestinal mucosal barrier function by promoting Th9/interleukin-9 expression.

OBJECTIVES: To investigate the effect of tumor necrosis factor ligand-related molecule 1A (TL1A) on the intestinal mucosal barrier in mice with chronic colitis. METHODS: Male TL1A-overexpressing transgenic mice and male C57BL/6 wild-type mice were used to establish a dextran sodium sulfate (DSS)-induced colitis model. The expression of occludin and claudin-1 was observed. Bacterial distribution in the intestinal mucosa and Th9/interleukin (IL)-9 expression were detected. In vitro co-culture systems of naive CD4+ T cells and Caco-2 cells were established and TL1A was added. Changes in transepithelial electrical resistance and IL-9 expression were measured. CD4+IL-9 cells were detected by flow cytometry. RESULTS: DSS mice showed a significant down-regulation of occludin and claudin-1 compared with controls. Expression levels of occludin, zonulin-1, and claudin-1 in the Caco-2+TGF-ß+IL-4+TL1A group were significantly lower than in the Caco-2+TGF-ß+IL-4 group. Bacterial distribution was clearly disordered in the DSS group. Transmembrane resistance of the Caco-2+TGF-ß+IL-4+TL1A group was significantly lower and IL-9 expression significantly higher than in the Caco-2+TGF-ß+IL-4 group. CONCLUSIONS: TL1A overexpression promotes destruction of the intestinal mucosal barrier in mice with chronic colitis. The underlying mechanism may be associated with the promoting role of TL1A in Th9/IL-9 expression, which further destroys the mucosal barrier.

How Pre-operative Sentinel Lymph Node Contrast-Enhanced Ultrasound Helps Intra-operative Sentinel Lymph Node Biopsy in Breast Cancer: Initial Experience.

We aimed to evaluate the value of sentinel lymph node contrast-enhanced ultrasound (SLN-CEUS) and surface tracing for the biopsy of intra-operative sentinel lymph nodes (SLNs). Between June 2015 and December 2017, a total of 453 patients with early invasive breast cancer were recruited. Patients received an intradermal injection of microbubble contrast agent around the areola on the day before surgery. The locations and sizes of lymphatic channels (LCs) and SLNs were marked on the body surface using gentian violet. Then, injection of double blue dye was performed half an hour before surgery. We compared the pathway of LCs and the location of SLNs obtained from SLN-CEUS and blue dye during surgery. Among the 453 patients, the mean numbers of LCs and SLNs detected by SLN-CEUS were 1.42 and 1.72, respectively, and the coincidence rate was 98.2% compared with blue dye during surgery. The median distance from the SLN to skin measured by pre-operative CEUS and blue dye was 1.95 ± 0.69 and 2.03 ± 0.87 cm (p = 0.35). There were three SLN enhancement in our research, including homogeneous enhancement, inhomogeneous enhancement and no enhancement, with the sensitivity, specificity, positive predictive value and negative predictive value of SLN-CEUS for the diagnosis of SLNs being 96.82%, 91.91%, 87.54% and 98.01%, respectively. SLN-CEUS with skin marking can identify the pathway of LCs and the location of the SLN before surgery, measure the distance from the SLN to skin and determine if the SLN is metastatic. SLN-CEUS can be used as an effective complement to the blue dye method.

Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain.

It is of great interest to identify new neurons in the adult human brain, but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial. In the present study, we have described the general configuration of the RMS in adult monkey, fetal human and adult human brains. We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain. The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin, polysialylated neural cell adhesion molecule and ßIII-tubulin. Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS, indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ. Interestingly, no neuroblasts are found in the adult human olfactory bulb. Taken together, our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.

5-HT induces enhanced phrenic nerve activity via 5-HT(2A) receptor/PKC mechanism in anesthetized rats.

Respiratory behavior expresses diverse forms of plasticity by altering breathing patterns. Failure of respiratory neuroplasticity often leads to malfunctions. Long-term facilitation (LTF), the most frequently studied model induced by episodic hypoxia to produce long-lasting enhancement of phrenic motor output, is thought to be serotonin 2A (5-HT(2A)) receptor-dependent. Previous studies have described 5-HT-induced prompt apnea in intact animals. However, the role of exogenous 5-HT in mediating respiratory neuroplasticity is less attended in vivo study. We hypothesized that an in vivo 5-HT challenge contributes to respiratory neuroplasticity. Here, we found that systemic bolus administration of 5-HT exerted an initial transient inhibition followed by marked facilitation, forming a biphasic pattern of phrenic nerve activity in artificially ventilated, midcervically vagotomized, and anesthetized adult rats. The facilitatory phase corresponded to the enhanced phrenic nerve activity that lasted for at least one hour after drug exposure, characterized as phrenic LTF (pLTF). The 5-HT-induced biphasic pattern and pLTF were 5-HT(2A) receptor-dependent and coupled to protein kinase C (PKC) activation. The initial inhibition of phrenic nerve activity was found to be nodose ganglion-associated, whereas the subsequent facilitation was carotid body-associated, establishing a peripheral inhibitory-facilitatory afferent balance. Immunoreactive expressions of 5-HT/5-HT(2A) receptors and phospho-PKC isoforms/PKC substrate provide morphological evidence of existence of a 5-HT/5-HT(2A) receptor/PKC mechanism in the nodose ganglion and the carotid body. We speculate that 5-HT challenge in vivo may contribute to respiratory neuroplasticity, to yield pLTF or augmented pLTF in animals with reduced or absent peripheral inhibitory inputs.

Immuohistochemical markers for pituicyte.

GFAP has long been adopted as the specific marker for pituicyte, a special type of astrocyte. GFAP and S100beta are two commonly used astrocyte markers. Their immunoreactivities differ in different regions of the brain. To our knowledge this issue has not been studied in pituicyte. In our preliminary study, we found that antibodies against GFAP and S100beta stained the pituicytes differently. A detailed investigation with both light and electron microscopic techniques was thus conducted in the rat. At light microscopic level, anti-GFAP and anti-S100beta stained 66.78% and 86.78% of the pituicytes, respectively. It was found at ultrastructural level that this difference was cell type specific. The parenchymatous pituicytes could be stained with antibodies against both GFAP and S100beta, whereas the fibrous pituicytes were only S100beta-immunoreactive. The functional significance of this cell type specificity remains to be elucidated.