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This paper used both methods of single parameter and Multi-parameter combination sensitivity analysis in groundwater numerical model parameter sensitivity analysis. With the examples of Jiaozuo, Henan province, choosing coefficient of permeability, porosity and longitudinal dispersion degree as factor, the paper analysis the main controlling factors of contaminant migration of Hexavalent chromium in groundwater. Single parameter sensitivity analysis results show that the permeability coefficient gives largest impact to the migration of hexavalent chromium. It is positively correlates with groundwater numerical model. The rest of the parameters assume the inverse correlation. Multi-parameter combination sensitivity analysis results show that the permeability coefficient has absolute advantage among various parameter combinations. Another conclusion is that longitudinal dispersion degree affects smaller on the process of hexavalent chromium pollutants migration, but the impact on the final density is bigger.

Due to the geological, hydrogeological feature along the main canal and construction characteristics of the inner drainage section engineering in the south-to-north water transfer project, pollutants might enter into the main canal with the groundwater, which may cause the main canal water quality risk. This study confirmed the rationality of the sensor research and guarantees the stability and accuracy of the groundwater detection based on the contrast of accuracy on the index of and comparison between groundwater sensor inspection and lab analysis data. For demonstration field monitoring at the same time, the running data was stable. Setting up demonstration project lays a solid foundation for building the key technology that is suitable for the water conveyance project of major water pollution control and water quality security system.

The contradictory is serious about the using balance of water recourse in Beijing Chaoyang district. The main phenomenon is excessive picking groundwater and water demand increases. Chaoyang Water Bureau had formulated the ground water rights market in for to stopping lower of ground water level. Water rights market configurated water resources and promoted using efficiency of water. The case of Chaoyang district water rights market will provide a reference for groundwater management and development of groundwater rights market.

Surface flow wetland with Reed planted in it was employed to treat micro-polluted water in Xinkai river, and effects of temperature, hydraulic retention time and growth of plants on the performance of surface flow wetland were studied. The results showed that COD removal of surface flow wetland was influenced by growth of plants and temperature, hydraulic retention time affected the performance of surface flow wetland obviously. NH4+-N removal of surface flow wetland was excellent and stable. Most of the area of the wetland system was under anaerobic or anoxic, Concentration of NO2--N and NO3--N in effluent stayed low. The denitrification was fully conducted but nitrification became a constraining factor. TP removal performance of surface flow wetland was ordinary. When Temperature was greater than 16°C, the hydraulic retention time was greater than the 3d and plants grew well, removal efficiencies of CODNH4+-N and TP were 22.45%,70.10% and 55.80% with concentration below 30.21mg/L1.82mg/L and 0.36mg/L, and the standards of Surface Water Grade V were satisfied.

The diesel engine vibration induced by piston impact force (also known as slaps) presents us very important information about piston-and-cylinder clearance and engine performance. However it is notorious difficult formaking an accurate measurement for the piston slaps due to the enormous interferences, reverberation, and complicated vibration responses. This paper presents an application of blind source separation technique to solve the problem. The method is based on one novel algorithm which uses blind source de-convolution algorithm. It can overcome the conventional blind source separation calculation drawbacks like local minimization value problems occurred with the fixed step response algorithm.The simulation and experiment results have indicated it can recover the corrupted signals and obtain the accurate piston slap signals at the measurement point.

The metal oxides modified Ni/γ-Al2O3 catalysts for glycerol steam reforming were prepared by impregnation. Characterization results of fresh catalysts indicated that the molybdates modification abated the acidity and the stronger metal-support interaction of Ni/γ-Al2O3 catalysts, leading to a stable catalytic activity. Especially, NiMoLa-CaMg/γ-Al2O3 (NiMoLa/CMA) catalyst exhibited no deactivation along with glycerol complete conversion to stable gaseous products containing 69% H2, 20% CO and 10% CO2 during time-on-stream of 42 h. TPO of spent Ni/γ-Al2O3 catalysts modified by different components showed that the carbon deposit on acidic sites and NiAl2O4 species led to catalysts deactivation. A lower reforming temperature and a higher LHSV and glycerol content were helpful to the production of syngas from GSR over NiMoLa/CMA; the reverse conditions would improve the formation of H2.

Microbes have deserved broader attention as causal factors in Alzheimer's disease (AD), a neurodegenerative disorder. The senescence-accelerated mouse prone 8 (SAMP8) strain, a spontaneous mice of accelerated aging, are considered a robust model for sporadic AD. LW-AFC, an herbal medicine, was prepared from LiuweiDihuang decoction, which is a classical traditional Chinese medicine prescription. Here, we showed that the treatment of LW-AFC improved cognitive impairments of SAMP8 mice, including spatial learning and memory ability, active avoidance response, and object recognition memory capability. Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units (OTUs) in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. The treatment of LW-AFC altered 22 (16 increased and 6 decreased) OTUs in SAMP8 mice and among them, 15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice. We further showed that there were 7 (3 negative and 4 positive correlation) OTUs significantly correlated with all the three types of cognitive abilities, at the order level, including Bacteroidales, Clostridiales, Desulfovibrionales, CW040, and two unclassified orders. LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice. Our results indicate that the effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.

Pain is an unpleasant sensory and emotional experience associated with various diseases. Extensive research has been conducted to find appropriate methods of relieving pain and improving the quality of life. However, the most commonly used pain-relieving agents such as opioid therapeutics are often associated with harmful side effects; moreover, users are prone to become addicted to these agents and may develop tolerance. Often, nonopioid therapeutics is only marginally effective, thus leading to a significant unmet medical need. Scientists have studied herbal medicines, finding more than 800 kinds of traditional Chinese medicine (TCM) to be effective in relieving pain while also creating several monomeric compounds to develop novel analgesic drugs. In this review, we summarize the representative TCM currently available for the treatment and modulation of pain. Ten different natural products, mainly herbs, used in Chinese medicine to relieve pain are discussed in light of the theories of TCM and modern pharmacology. We hope that this review will provide valuable information for future studies on the potential of TCM in alleviating pain.

Liuwei Dihuang decoction (LW) has been used in traditional Chinese medicine (TCM) for more than 900years to prevent and treat various diseases with characteristic features of kidney yin deficiency. To date, LW has been commonly prescribed in TCM as therapy or adjuvant therapy against various diseases. To elucidate the pharmacological characteristics and mechanism of action of this formula, studies have been conducted on the pharmacological effects and chemical profiles (including bioactive ingredients) to investigate the role of LW in the neuroendocrine immunomodulation (NIM) network. In this review, we provide an overview of the pharmacological effects of LW on the NIM network, particularly on learning and memory, immunomodulation, and neuroendocrine-immune interactions, including the effects of LW on the central nervous system, endocrine system, and immune system. We also discuss advances in related chemical studies, especially those identifying the bioactive components of LW and their unique combinational effects on the immune system. Our experimental results indicate that LW exerts a broad spectrum of pharmacological effects, by modulating and restoring the balance of the NIM network disturbed by several pathological factors.

Pain is an unpleasant sensory and emotional experience associated with various diseases. Extensive research has been conducted to find appropriate methods of relieving pain and improving the quality of life. However, the most commonly used pain-relieving agents such as opioid therapeutics are often associated with harmful side effects; moreover, users are prone to become addicted to these agents and may develop tolerance. Often, nonopioid therapeutics is only marginally effective, thus leading to a significant unmet medical need. Scientists have studied herbal medicines, finding more than 800 kinds of traditional Chinese medicine (TCM) to be effective in relieving pain while also creating several monomeric compounds to develop novel analgesic drugs. In this review, we summarize the representative TCM currently available for the treatment and modulation of pain. Ten different natural products, mainly herbs, used in Chinese medicine to relieve pain are discussed in light of the theories of TCM and modern pharmacology. We hope that this review will provide valuable information for future studies on the potential of TCM in alleviating pain.

The flow of the hydrogen has played an important role in the heat exchange in the inner bell. In this research, we have studied the volume distribution of the hydrogen in the inner bell through numerical simulation method, and we get the volume distribution law of the hydrogen when we change the axial angle and the tangential angle of the velocity of the hydrogen flowing into the inner bell while we do not change the speed of the hydrogen. This research could provide theory reference for the design and application of the structure of the coil base of the high performance hydrogen bell-type annealers later.

This paper analyzes the current energy structure and coal we use, based on clean coal technology in China, one of the current technology development status and prospects of coal were analyzed, and highlights China's Hunan province a coal for flue-cured tobacco production - biomass briquette mix, production test proved its superior performance, the desulfurization rate, burn rate of more than 90%, respectively, and 98%, suitable for promotion.

Ethnopharmacological relevance Liuwei Dihuang decoction (LW) is a typical traditional Chinese medicine (TCM) prescription and consists of six herbs including Rehmannia glutinosa Libosch. (family: Scrophulariaceae), Cornus officinalis Sieb. (family: Cornaceae), Dioscorea opposite Thunb. (family: Dioscoreaceae), Alisma orientale (G. Samuelsson) Juz (family: Alismataceae), Poria cocos (Schw.)Wolf (family: Polyporaceae) and Paeonia suffruticosa Andrews (family: Paeoniaceae). It has long been used clinically in treatment of many kinds of diseases with the sign of Yin insufficiency of kidney. Aim of the study Our previous pharmacological studies demonstrated that LW possesses effect of ameliorating the decline of the learning and memory in senescence accelerated mouse/prone 8 (SAMP8), but the mechanism has not been well established. LW-containing serum (LWCS) is used in the current study to elucidate the possible mechanisms. Materials and methods 6-month-old SAMP8 was used in this study to investigate the effect of LWCS on the induction of long-term potentiation (LTP). Primary cultured hippocampal neurons were used in this study to investigate the effects of LWCS on [Ca2+]i, ICa and N-Methyl- d -aspartate (NMDA)-evoked currents. [Ca2+]i was imaged using Fluo-3 and whole-cell patch recordings were applied to study the ICa and NMDA-evoked currents. Results We find that LWCS facilitates the induction of LTP in hippocampal slices of 6-month-old SAMP8. In primary cultured hippocampal neurons, LWCS increases intracellular [Ca2+]i, the ICa is suppressed by LWCS, and NMDA-evoked currents are promoted. Conclusion These results indicate that LW improves the synaptic plasticity by inhibiting voltage-dependent calciumchannels (VDCCs) and promoting the function of NMDA receptors. This improvement might be one of the mechanisms contributing to cognitive improvement effect of LW.

The senescence accelerated mouse prone 8 (SAMP8), an animal model of Alzheimer's disease, has amyloid-β deposition in the brain. This study showed that β-secretase activity increased age-dependently in cerebral cortex of SAMP8 and SAMP8's control, SAM resistant/1 (SAMR1), and was higher in the hippocampus of SAMP8 than that of age-matched SAMR1. Cathepsin D activity also increased age-dependently in the cerebral cortex of SAMP8. There was no significant difference between SAMP8 and SAMR1 with regards to activity of cathepsin B. β-secretase activity had a positive correlation with cathepsin D activity in the cerebral cortex of SAMR1 and SAMP8. There was a tendency toward decreased mRNA expression of BACE1, cathepsin D, and cathepsin B in the hippocampus of SAMR1 and SAMP8 with aging. mRNA expression of cathepsin B was elevated significantly in the cerebral cortex of SAMP8 at 2 and 6 months of age compared to that of age-matched SAMR1, and similarly so was cathepsin D at 2 months. This data showed there was no correlation between mRNA expression and activity of β-secretase, cathepsin D, and cathepsin B in the brain of SAMR1 and SAMP8 with age. These findings also indicate it was cathepsin D, not cathepsin B, that contributed to β-secretase activity and the increased amyloid-β production in the SAMP8 brain. In addition, it was necessary to take into account the target selectivity of BACE1 and cathepsin D, not necessary to detect the mRNA expression, when SAMP8 was used as an animal model to determine the effect of β-secretase inhibitor.

In this study, we investigated the performance of BALB/c mice in Morris water maze task under two different illumination (bright and dim light) conditions. The results show that BALB/c mice could not complete the Morris water maze task under bright light (BLC), but performed very well under dim light (DLC). Animals that swam under BLC had a higher serum corticosterone level than those under DLC. Animals pretrained under DLC had a lower serum corticosterone level than those directly exposed to BLC. Our results also show that animals under BLC had a higher level of thigmotaxis (a behavioral anxiety measure during testing) than under DLC. Correlation analysis shows that corticosterone and thigmotaxis levels have a positive correlation with escape latency, indicating that corticosterone and thigmotaxis levels have a negative correlation with learning/memory performance. These results suggest that BALB/c mice have the ability to learn a spatial task; under BLC, they performed poorly owing to a high level of thigmotaxis.

Objectives: Multi-drug resistance (MDR) to chemotherapy remains a major obstacle to overcome in the successful treatment of patients with cancers. It was recently discovered that Leptomycin B (LMB) reduces the paclitaxel-induced MDR in CCRF-CEM/Taxol cells. However, the mechanism remains unclear. Here we sought to explore the mechanism of LMB to reduce the MDR induced by paclitaxel. Results: LMB has remarkable cytotoxic effects in both sensitive CCRF-CEM and resistant CCRF-CEM/Taxol cell lines. The paclitaxel-induced MDR was reduced by 0.013 μm of LMB. Lower concentration of LMB regulated cell cycle progress, in situ expressions of P-gp, MRP1, and LRP, expression of CRM1, and localization of P-gp and CRM1 in CCRF-CEM/taxol cells. Study Design: Cytotoxicity of LMB on cancerous cell lines was determined by MTT assay. Cell cycle progress and in situ expressions of P-gp, MRP1, and LRP were analyzed by flow cytometry. Expression of CRM1 in the cells was examined by Western blot. And co-localization between P-gp and CRM1 was determined by laser confocal microscopy. Conclusion: The paclitaxel-induced MDR of CCRFCEM/Taxol cells was reduced by lower concentration of LMB. The mechanisms might be related to decreasing in situ expression of drug transporter proteins, promoting cell cycle progress, and altering co-localization between P-gp and CRM1 in the resistant cells.

The heating bell with burners is an important heating device for the high performance hydrogen bell-type annealers. The arrangement of the burners has an important impact on the heating effect. In this study, we simulated a series of model with different location of burners under the same quantity of burners and the same heating power. The result shows: (1) Under the same quantity of burners and the same heating power, when we increase the number of rows of burners, the maximum temperature inside the furnace could be reduced, and the temperature distribution will become more uniform; (2)When we fixed the number of the row of the burners, if we move the upper burners to higher position to make the arrangement of burners more uniform, the temperature distribution inside the furnace will be more uniform, this will be good for the heat transfer to the higher parts of the annealers, and this will accelerate the heating process, improve the efficiency of annealing, reduce fuel consumption, and extend the life of the inner bell.

Given the ambiguity of the type and classification in groundwater quality standards, this paper based on fuzzy mathematics theory, take TDS, fluoride and other components as the nine evaluation factors, determine its weight according to the pollution of different factors on water quality; using fuzzy membership to describe the classification boundaries of the evaluation in water quality. Established a number of pollution assessment factors of fuzzy sets such as evaluation set, membership function and weight set;after the compound operation of fuzzy matrixes, using the maximum membership degree law, to evaluate the groundwater quality of a monitoring well in study area ,the conclusions are objective.

Inertia moment of engine is a quite important parameter for power measuring without load, instantaneous speed calculating and in cylinder pressure reconstruction. In order to get this important parameter, a new method named instantaneous speed fluctuation comparison is brought out. The detail theory and approach is introduced. After experiment on the 6135 diesel, the validity of the method is proved, and the error of the method is analyzed.

Vibration signal of rolling-element bearing is random cyclostationarity when a fault develops, the proper analysis of which can be used for condition monitor. Cyclic spectrum is a common cyclostationary analysis method and has a great many algorithms which have distinct efficiency in different application circumstance, two common algorithms (SSCA and FAM) are compared in the paper. The FAM is recommended to be used in diagnosing rolling-element bearing fault via calculation of simulation signal in different signal to noise ratio. The cyclic spectrum of practice signal of rolling-element bearing with inner-race point defect is analyzed and a new characteristic extraction method is put forward. The preferable result is acquired verify the correctness of the analysis and indicate that the cyclic spectrum is a robust method in diagnosing rolling-element bearing fault.

SpaceWire is used for on-board satellite networks. It is proposed by the ESA as the basis for future data-handing architectures. It takes an indispensable role for the shortage of bandwidth of bus among data processing. Based on the research of SpaceWire Network, some parameters, such as delay, bit error ratio, bandwidth and throughput, a new scheme of the testing about the parameters of SpaceWire was proposed. Then its implementation technology was analyzed and explained.

SpaceWire is becoming a popular solution for satellite high-speed data buses, because it is a simple standard that provides great flexibility for a wide range of system requirements. This article introduces the driver design for the SpaceWire communication device based on embedded Linux, including the analysis of the driver structure, the design of the interfaces between the upper and lower layers and the responding strategy for interrupts. In the realization link, we choose a mainstream developing platform and realize a camera capturing system for testing, and analyse the test result.

A glycoconjugate designated as LbGp5B was isolated from the fruit of Lycium barbarian L. and purified to homogeneity by gel filtration. LbGpSB is composed of rhamnose (Una), arabinose (Ara), galactose (Gal), glucose (Glc), galacturonic add (GalA) and seventeen amino adds. The molecular weight of LbGpSB was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and by matrix-assisted laser desorption/ionization (MALDI) time of fight (TOF) mass spectrometry (MS). The preliminary experiments showed that LbGpSB promoted splenocyte proliferation in mice and inhibited the peroxidation of low density lipoprotein (LDL).

The detailed structure of an O-glycan derived from the fruit of Lycium barbarum L. was elucidated based on glycosidic linkage analysis, complete and partial acid hydrolysis, 1H-NMR and 13C NMR spectroscopy. According to the experiments, the carbohydrate was in the form of polysacchride (arabinogalactan) chains with highly branched 3, 4-galactans and terminal arabinofuranosyl substituents. The immuno-modulating mechanism of glycoconjugate and its glycan were investigated using tritium thymidine incorporation assay, flow cytometry assay and electrophoretical mobility shift assay (EMSA). The results suggested that the immunoactive components of the fruit of Lycium barbarum L. could enhance the splenocyte proliferation in normal mice and the effects of glycan chain were stronger than those of glycoconjugate. The target cell was most likely to be B-lymphocyte, on which existed receptor binding site acting with the glycan. In addition, the immuno-stimulatory effect of glycoconjugate (LbGp4) and its glycan (LbGp4-OL) was associated with activating the expression of nuclear factor KB (NF-KB) and activator protein 1 (AP-1).

Growing evidence shows that the neuroendocrine immunomodulation (NIM) network plays an important role in maintaining and modulating body function and the homeostasis of the internal environment. The disequilibrium of NIM in the body is closely associated with many diseases. In the present study, we first collected a core dataset of NIM signaling molecules based on our knowledge and obtained 611 NIM signaling molecules. Then, we built a NIM molecular network based on the MetaCore database and analyzed the signaling transduction characteristics of the core network. We found that the endocrine system played a pivotal role in the bridge between the nervous and immune systems and the signaling transduction between the three systems was not homogeneous. Finally, employing the forest algorithm, we identified the molecular hub playing an important role in the pathogenesis of rheumatoid arthritis (RA) and Alzheimer&rsquo, s disease (AD), based on the NIM molecular network constructed by us. The results showed that GSK3B, SMARCA4, PSMD7, HNF4A, PGR, RXRA, and ESRRA might be the key molecules for RA, while RARA, STAT3, STAT1, and PSMD14 might be the key molecules for AD. The molecular hub may be a potentially druggable target for these two complex diseases based on the literature. This study suggests that the NIM molecular network in this paper combined with the forest algorithm might provide a useful tool for predicting drug targets and understanding the pathogenesis of diseases. Therefore, the NIM molecular network and the corresponding online tool will not only enhance research on complex diseases and system biology, but also promote the communication of valuable clinical experience between modern medicine and Traditional Chinese Medicine (TCM).

Increasing evidences have indicated that STUB1 may be closely linked to Alzheimer's disease (AD). Senescence-accelerated mice (SAM) prone/8 (SAMP8) is a generally acknowledged animal model for senescence and AD, and SAM resistant/1 (SAMR1) is its control. In this study, we investigated the detailed expression of STUB1 in the brain of SAMP8 with aging and its responses to five anti-AD traditional Chinese medicinal (TCM), using real-time fluorescence quantitative PCR and Western blot technique. Results showed that with the aging process, both mRNA and protein expression of STUB1 in the cerebral cortex and hippocampus from SAMR1 increased after 2 months, while they decreased in brain tissues from SAMP8 after 6 months. Compared with SAMR1, the mRNA and protein expression of STUB1 decreased after 10 months in SAMP8 but could be up-regulated by the five anti-AD TCM used in this study. These results indicated that the expression of STUB1 in the brain of SAMP8 was abnormal and this abnormality could be reversed by anti-AD TCM. The data suggested that a deficiency in STUB1 may lead to a reduction in aberrant protein scavenging, causing abnormal protein accumulation in the brain of SAMP8. Thus, STUB1 might be a potential target for anti-AD TCM.

Liuwei Dihuang decoction (LW), a traditional Chinese medicinal prescription, enhances the cognitive function of CNS by significant modulating effects on some of the gene expressions. Expressions of genes, such as DUSP12, NSF, STUB1, CaMKIIalpha, AMFR, UQCRFS1 and other 11 novel genes without any functional clues changed significantly. These genes are involved in the protein-tyrosine phosphatase family, the AAA (ATPases associated with diverse cellular activities) gene family, the serine/threonine protein kinases family, ubiquitin ligase, mitochondrial function and so on.

Polyphenols, which are naturally present in plants, have been studied for their chemical and pharmacological properties. Polyphenols have been found to exhibit various bioactivities such as antioxidant, free radical scavenging and anti-inflammatory effects, in addition to regulating the intracellular free calcium levels. These bioactivities are related to the underlying mechanisms of ischaemic heart diseases. Pharmacological studies have proven polyphenols to be effective in treating cardiovascular diseases in various ways, particularly ischaemic heart diseases. Based on their mode of action, we propose that some polyphenols can be developed as drugs to treat ischaemic heart diseases. For this purpose, a strategy to evaluate the therapeutic value of drugs for ischaemic heart diseases is needed. Despite several advances in percutaneous coronary intervention (PCI), the incidence of myocardial infarction and deaths due to cardiovascular diseases has not decreased markedly in China. Due to their pleiotropic properties and structural diversity, polyphenols have been of great interest in pharmacology. In the present review, we summarize the pharmacological effects and mechanisms of polyphenols reported after 2000, and we analyse the benefits or druggability of these compounds for ischaemic heart diseases.

The effect of Liuwei Dihuang decoction (LW), a traditional Chinese medicine (TCM) prescription, on voltage-dependent currents and synaptic transmission were investigated in cultured hippocampal neurons of rat by whole-cell patch clamp recording technique. After application with serum from LW-treated rats, termed LW-containing serum (LWCS) for 48 h, the amplitude of delay rectifying K+ current (IK) and voltage-gated Ca2+ current (ICa) decreased. While the frequency of spontaneous excitatory post-synaptic current (sEPSC) and miniature excitatory post-synaptic current (mEPSC) increased significantly. Yet the amplitude of voltage-depended Na+ current (INa) and transient outward K+ current (IA), membrane capacitance and resistance remained unchanged. The results indicated that LWCS possessed the effect of modulating or improving neuronal and synaptic function, which possibly contribute to the cognition enhancing effect of LW.

Selective blockers of the N-type voltage-sensitive calcium (CaV) channels are useful in the management of severe chronic pain. Here, the structure and function characteristics of a novel N-type CaV channel blocker, SO-3, are reviewed. SO-3 is a 25-amino acid conopeptide originally derived from the venom of Conus striatus, and contains the same 4-loop, 6-cysteine framework (C-C-CC-C-C) as O-superfamily conotoxins. The synthetic SO-3 has high analgesic activity similar to É-conotoxin MVIIA (MVIIA), a selective N-type CaV channel blocker approved in the USA and Europe for the alleviation of persistent pain states. In electrophysiological studies, SO-3 shows more selectivity towards the N-type CaV channels than MVIIA. The dissimilarity between SO-3 and MVIIA in the primary and tertiary structures is further discussed in an attempt to illustrate the difference in selectivity of SO-3 and MVIIA towards N-type CaV channels.

1 Whole-cell currents in cultured hippocampal neurons were recorded to investigate the effects of SO-3, a new O-superfamily conopeptide derived from Conus striatus, on voltage-sensitive channels. 2 SO-3 had no effect on voltage-sensitive sodium currents, delayed rectifier potassium currents, and transient outward potassium currents. 3 Similar to the selective N-type calcium channel blocker ω-conotoxin MVIIA (MVIIA), SO-3 could concentration-dependently inhibit the high voltage-activated (HVA) calcium currents (ICa). 4 MVIIA(3 μM), 10 μM nimodipine, and 0.5 μMω-agatoxin IVA (Aga) could selectively block the N-, L-, and P/Q-type ICa, which contributed ∼32, ∼38, and ∼21% of the HVA currents in hippocampal neurons, respectively. About 31% of the total HVA currents were inhibited by 3 μM SO-3. SO-3 (3 μM) and 3 μM MVIIA inhibited the overlapping components of HVA currents, whereas no overlapping component was inhibited by 3 μM SO-3 and 10 μM nimodipine, or by 3 μM SO-3 and 0.5 μM Aga. Also, 3 μM SO-3 had no effect on R-type currents. 5 SO-3 had less inhibitory effects on non-N-type HVA currents than MVIIA at higher concentrations (30 and 100 μM). 6 The inhibitory effects of SO-3 and MVIIA on HVA currents were almost fully reversible. However, the recovery from block by MVIIA was more rapid than recovery from block by SO-3. 7 It is concluded that SO-3 is a new ω-conotoxin selectively targeting N-type voltage-sensitive calcium channels. Considering the significance of N-type calcium channels for pain transduction, SO-3 may have therapeutic potential as a novel analgesic agent. British Journal of Pharmacology (2005) 145, 728–739. doi:10.1038/sj.bjp.0706223

Senescence-accelerated mouse (SAM) have been used as animal models in the studies of senescence and age-associated disorders for many years. The typical feature of SAM-prone8 (SAMP8), a substrain of SAM, is the development of early onset of learning and memory deficit during its aging process, while SAM-resistant1 (SAMR1) shows normal aging process. To study the synaptic mechanism underlying the cognitive deterioration of SAMP8, whole-cell recording technique was used to compare the synaptic function of cultured SAMP8 hippocampal neurons with that of SAMR1 in our experiments. Paired-pulse depression (PPD), a simple form of use-dependent synaptic plasticity, is measured in autapse in response to paired stimulation. Those autapses in tests possessed the compatible evoked EPSC in amplitude. However, the degree of PPD in cultured hippocampal neurons of SAMP8 was far larger and the time constant of the autapse recovery from PPD was longer than those of SAMR1. In addition, mEPSC recorded in autapse were lower in frequency in SAMP8 compared with that of SAMR1, but with the similar amplitude, suggesting that presynaptic mechanism was involved. These results suggested that the synaptic plasticity of hippocampal neurons of SAMP8 is deficient compared to that of SAMR1, which may be caused by some kind of presynaptic functional disorders.

Liuwei Dihuang decoction (LW) is a classical traditional Chinese medicinal prescription used clinically in the treatment of the diseases manifesting “Kidney-Yin” deficiency syndrome such as cancer, diabetes, autoimmune diseases, and the diseases related to the disorder of endocrine function including climacteric syndrome, sexual inadequacy, sterility and hyperplasia of prostate, etc., in traditional Chinese medicine in China. In this study, age-related functional change of hypothalamus–pituitary–ovary (HPO) axis and the effect of LW were studied in senescence-accelerated mouse (SAM). The results showed that the oestrus cycle and diestrus of SAM-prone/8 (SAMP8) were significantly prolonged from 5 months old. The level of serum estrogen was significantly higher in 3-month-old SAMP8 than that in age-matched SAMR1, and markedly declined from 5 months old and kept no significant change from 5 to 11 months old. The pituitary LH was markedly raised from 7 months old. Oral administration of LW improved the shortened estrus, increased the ovary weigh and significantly reduced the pituitary content of LH in 9-month-old SAMP8. These results suggested that the imbalance of HPO axis occurs at the early age in SAMP8 and LW modulates or improves the imbalance of HPO axis in SAMP8 during aging process.

Thymosin alpha-1 (Talpha1) not only possesses immunoregulatory properties in periphery but also is expressed in the central nervous system (CNS) and affects the function of the CNS. To further elucidate the role of Talpha1 in the CNS, the whole-cell recording technique was used to observe the effect of Talpha1 on the spontaneous excitatory synaptic transmission in cultured rat hippocampal neurons. The results showed that acute treatment with Talpha1 significantly enhanced the frequency of AMPA-mediated spontaneous excitatory postsynaptic current (sEPSC) at the concentrations of 1 and 10 microg/ml and also enhanced the frequency of AMPA-mediated miniature excitatory postsynaptic current (mEPSC) at 10 microg/ml. However, the amplitude of both sEPSC and mEPSC were not changed by Talpha1. Those results suggested that Talpha1 involves in the regulation of excitatory synaptic transmission in hippocampal neurons, which contribute to its neurophysiological function in the CNS.

Glycosylation is one of the most common eukaryotic post-translational modifications, and aberrant glycosylation has been linked to many diseases. However, glycosylation and glycome analysis is a significantly challenging task. Although several lines of evidence have indicated that protein glycosylation is defective in Alzheimer's disease (AD), only a few studies have focused on AD glycomics. The etiology of AD is unclear and there are no effective disease-modifying treatments for AD. In this study, we found that the object recognition memory, passive avoidance, and spatial learning and memory of senescence-accelerated mouse prone 8 (SAMP8) strain, an AD animal model, were deficient, and LW-AFC, which was prepared from the traditional Chinese medicine prescription Liuwei Dihuang decoction, showed beneficial effects on the deterioration of cognitive capability in SAMP8 mice. Forty-three and 56 N-glycan were identified in the cerebral cortex and serum of SAMP8 mice, respectively. The N-glycan profile in SAMP8 mice was significantly different from that of senescence accelerated mouse resistant 1 (SAMR1) strains, the control of SAMP8 mice. Treatment with LW-AFC modulated the abundance of 21 and 6 N-glycan in the cerebral cortex and serum of SAMP8 mice, respectively. The abundance of (Hex)3(HexNAc)5(Fuc)1(Neu5Ac)1 and (Hex)2(HexNAc)4 decreased in the cerebral cortex and serum of SAMP8 mice compared with SAMR1 mice, decreases that were significantly correlated with learning and memory measures. The administration of LW-AFC could reverse or increase these levels in SAMP8 mice. These results indicated that the effects of LW-AFC on cognitive impairments in SAMP8 mice might be through modulation of N-glycan patterns, and LW-AFC may be a potential anti-AD agent.

As an important neurotransmitter, adenosine displays its functions by acting on the adenosine receptors. Recent studies have shown that the distribution, expression and balance among subtypes of adenosine receptors are closely related with cognitive activities, and changes of adenosine receptors play key roles in neurodegenerative disorders including Alzheimer's disease. It has been pointed out that prolonged activation of adenosine receptors by high level adenosine may lead to the disturbance of balance among adenosine receptor subtypes. This imbalance mainly performed as increased expression of A2a receptor and decreased expression of A1 receptor, and enhancement of the excitatory signals mediated by A2a receptor and weakened inhibitory signals mediated by A1 receptor. Changes of these two subtypes of adenosine receptors may lead to a lot of disorders of neurological activities which developed into dysfunction of cognition to the end. These findings imply that the potential of maintaining the balance among adenosine receptors on the treatment of AD would facilitate both the revealing of the mechanism and the cure of AD.

The present one-drug, one-target paradigm for anti-Alzheimer’s disease (AD) treatment appears to be clinically unsuccessful, the combinational targets which composed of several biomolecules based o...

To explore the etiologic characteristics of adult patients with community-acquired pneumonia (CAP) in Beijing.A multicenter cohort of 510 adult CAP patients were enrolled from Beijing during the period of November 2010 to May 2012. Multiplex polymerase chain reaction (PCR), real-time fluorescence quantitative PCR and legionella urinary antigen were used to detect common respiratory viruses, Mycoplasma pneumoniae and legionella respectively. Bacteria were detected by sputum culture, blood culture and Streptococcus pneumoniae urinary antigen. Statistical analyses were performed for the etiologic characteristics and seasonal distribution of detected pathogens.Pathogens were detected in 240/500 (47.1%) study patients. The mixed infection of different pathogens was present in 42 cases (8.2%), viruses in 164 (32.2%), Mycoplasma pneumoniae in 91 (17.8%), bacteria in 26 (5.1%) and Legionella in 3 (0.6%). Among 164 patients infected with viruses, 194 viral strains were detected. Influenza virus represented the greatest proportion with 105 (54.1%) in viral infections. Between November 2010 to October 2011, Influenza A infections increased gradually in November 2010, peaked in February 2011 and declined by March 2011 in China. Mycoplasma pneumoniae was predominant in winter and spring.There is a high detection rate of virus and Mycoplasma pneumoniae in adult CAP patients in Beijing. And more consideration should be given to influenza virus and Mycoplasma pneumoniae infections in winter and early spring.

Harboring the behavioral and histopathological signatures of Alzheimer's disease (AD), senescence accelerated mouse-prone 8 (SAMP8) mice are currently considered a robust model for studying AD. However, the underlying mechanisms, prioritized pathways and genes in SAMP8 mice linked to AD remain unclear. In this study, we provide a biological interpretation of the molecular underpinnings of SAMP8 mice. Our results were derived from differentially expressed genes in the hippocampus and cerebral cortex of SAMP8 mice compared to age-matched SAMR1 mice at 2, 6, and 12 months of age using cDNA microarray analysis. On the basis of PPI, MetaCore and the co-expression network, we constructed a distinct genetic sub-network in the brains of SAMP8 mice. Next, we determined that the regulation of synaptic transmission and apoptosis were disrupted in the brains of SAMP8 mice. We found abnormal gene expression of RAF1, MAPT, PTGS2, CDKN2A, CAMK2A, NTRK2, AGER, ADRBK1, MCM3AP, and STUB1, which may have initiated the dysfunction of biological processes in the brains of SAMP8 mice. Specifically, we found microRNAs, including miR-20a, miR-17, miR-34a, miR-155, miR-18a, miR-22, miR-26a, miR-101, miR-106b, and miR-125b, that might regulate the expression of nodes in the sub-network. Taken together, these results provide new insights into the biological and genetic mechanisms of SAMP8 mice and add an important dimension to our understanding of the neuro-pathogenesis in SAMP8 mice from a systems perspective.

β-site amyloid-β protein precursor cleaving enzyme 1 (BACE1) is the first protease and the rate limiting enzyme in the genesis of amyloid-β (Aβ). This protein remains an important potential disease-modifying target for the development of drugs to treat Alzheimer's disease (AD). We are pursuing potent BACE1 inhibitors in an effort to identify suitable AD drug candidates. Our results have shown that the novel compound VIa exhibits potent inhibitory effects with IC50 = 5.9 nM and displays 30.8-fold, 7500-fold and 17533-fold selectivity against the other aspartic proteases BACE2, cathepsin D and renin, respectively. In cellular assays, VIa moderately reduces Aβ production: Aβ(1-40) with an IC50 = 143 nM and 1 nM VIa reduced Aβ(1-42) by 40.17%. Concomitant with VIa inhibiting the β-cleavage of amyloid-β protein precursor (AβPP), VIa increases the production of sAβPPα with an approximate EC50 of 16.5 nM. In testing this compound's efficacy in vivo, the oral administration of VIa resulted in a significant decrease in Aβ(1-40) and Aβ(1-42) in the blood of a mouse model of AD by 17.5-72.44% and 14.5-80.32%, respectively. This indicates that the novel compound VIa is a small, potent, selective, and non-peptidic BACE1 inhibitor.

Alzheimer's disease (AD) is a widespread and devastating progressive neurodegenerative disease. Disease-modifying treatments remain beyond reach, and the etiology of the disease is uncertain. Animal model are essential for identifying disease mechanisms and developing effective therapeutic strategies. Research on AD is currently being carried out in rodent models. The most common transgenic mouse model mimics familial AD, which accounts for a small percentage of cases. The senescence-accelerated mouse prone 8 (SAMP8) strain is a spontaneous animal model of accelerated aging. Many studies indicate that SAMP8 mice harbor the behavioral and histopathological signatures of AD, namely AD-like cognitive and behavioral alterations, neuropathological phenotypes (neuron and dendrite spine loss, spongiosis, gliosis and cholinergic deficits in the forebrain), β-amyloid deposits resembling senile plaques, and aberrant hyperphosphorylation of Tau-like neurofibrillary tangles. SAMP8 mice are useful in the development of novel therapies, and many pharmacological agents and approaches are effective in SAMP8 mice. SAMP8 mice are considered a robust model for exploring the etiopathogenesis of sporadic AD and a plausible experimental model for developing preventative and therapeutic treatments for late-onset/age-related AD, which accounts for the vast majority of cases.

Paeoniflorin (PF) is the chief active component of paeonia, with diverse pharmacological actions and wide application. Recently, the effect of PF on nervous system has attracted increasingly more attention. According to current study findings, PF can ameliorate the decline of memory and learning capacities in many dementia model animals, and have effect in protecting the cerebral ischemia injury, treating Parkinson's disease, reliving pain and improving neural synapse plasticity. Thought its mechanism has not been clarified, current findings show that adenosine A1 receptor plays an important role, while M cholinergic receptor, opiate receptor, calcium ion channel and NF-KB may also play a part in paeoniflorin's effect on nervous system.

Repetitive transcranial of magnetic stimulation (rTMS), as a new electrophysiological technique, has been used in treating neurological and psychiatric diseases in clinical. In recent years, rTMS has also been employed to explore the treatment options for post stroke cognitive impairment (PSCI). Studies showed that rTMS was beneficial to recovery of post-stroke aphasia, improvement of memory dysfunction and alleviation of hemispatial neglect. Moreover, it is safe for patient within the recommended parameters of safety guidance. rTMS exerts therapeutic effects by interfering with the reconstruction of cortical network, improving the cerebral blood flow and metabolism, adjusting the ion balance by modulating cortical excitability. In addition, rTMS could enhance synaptic plasticity, inhibit the apoptosis, and regulate the transmission of a variety of neurotransmitters. It was reviewed that the basic principles of rTMS, the efficacy, safety and mechanism of rTMS in the treatment of PSCI, as well as the current problems and prospects in this paper.

The hippocampus has important roles in learning and memory. Many in vivo experiments require accurate location of a certain region of the hippocampus, long-term potentiation (LTP) recording being one of them. In vitro and in vivo studies can be used to measure LTP in the hippocampus. It is more difficult in vivo to locate the specific brain region than in vitro. Location of the dentate gyrus (DG) and perforant path (PP) is usually achieved using brain stereotaxic atlasses. Because the data in the atlasses were obtained from a particular rat/mouse strain (Rat: adult Wistar, 290 g; Mouse: adult C57BL/J6, 26-30 g), the data in atlases could not be easily applied in all the different other strains of these species. We describe a method that uses landmarks on the skull to locate these structures in both species, which has been successfully applied in BALB/c mice, KM mice, SAMP8, SAMR1 and Wistar rats; making it a reliable and useful means of locating the DG and PP.