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Traditional Chinese Medicine prescription Suanzaoren decoction (SZRD) is composed of Ziziphi Spinosae Semen, Chuanxiong Rhizoma, Anemarrhenae rhizoma, Poria and Licorice. It was used to treat central nervous system diseases such as insomnia and anxiety for thousands of years. This paper aims to systematically understand varieties and quantities of compounds and clarify chemical components of SZRD, subsequently to further provide the reference for phytochemistry and pharmacology researches of SZRD. Our results showed that SZRD contained 145 components, including flavonoids, triterpenoids, steroids, coumarins, phthalides, and volatile oils, etc., while five-single herbs contain 1104 components. Only in terms of compound number, there were 80 common components in SZRD and its five herbs, which accounted for 6.8% of total compounds in all 5 herbs and 55.2% of compounds in SZRD. The components of SZRD were not simply the sum of one in every single herb. It is necessary to perform parallel studies among SZRD and its herbs. This review discussed the problems that existed in the chemical research of SZRD and pointed out the direction for its further research.

Anxiety is a common, universal disease caused by psychological and environmental factors. There are medications available to treat anxiety disorders, but these are accompanied by problems such as addiction and withdrawal difficulties. Suanzaoren Prescription (SZRP) is often used to treat anxiety disorders in traditional Chinese medicine clinical practice. However, its therapeutic mechanism remains unclear. This work aims to identify potential core therapeutic targets and predict major bioactive compounds by means of network pharmacology, screen compounds that may bind to anxiety targets by molecular docking methods, and validate and evaluate possible therapeutic mechanisms of compounds for anxiety in vitro cell experiments. Datebase TCMSP, BATMAN-TCM, ETCM, TCMGeneDIT and TCMID was used to obtain SZRP compounds, while TCMSP, BATMAN-TCM and ETCM were used to obtain target of compounds. The targets of anxiety disorders were obtained through database TTD, OMIM, PharmgKB, CTD, DrugBank and Metacore. The network diagram is drawn by Cytoscape 3.7.2 software and STRING. Biological process and KEGG pathway analysis were conducted by MetaCore and NIMNT. AutoDock Vina software was used to conduct molecular docking. The calcium Flux assay was employed to detect the activation of compounds on CNR1 in cell line CHO-K1/CNR1/Gα15. The 545 compounds in SZRP were collected. We found there were 1050 potential targets of these compounds in SZRP which involved in brain disease, mood disorder, endocrine system disease, bipolar disorder, etc. There were 117 potential targets of SZRP against anxiety (such as DRD2, BDNF, COMT, SLC6A4, HTR1A, etc.), which played the roles in regulation of membrane potential and synaptic transmission, nicotine addiction, retinol metabolism, GABAergic and serotonergic synapse, etc. The results of molecular docking indicated there were the biggest affinity between Jujuboside B and DRD2, BDNF, COMT, SLC6A4, Anemarsaponin B_qt and HTR1A, n-methylasimilobine and MAPK3. Based on cell CHO-K1/CNR1/Gα15 and calcium flux technique, we found Chrysophanol, Kaempferol and Emodin have activation effects on CNR1 with EC50 138.3µM, 52.28µM and 56.86µM respectively. These results indicated that the effects of SZRP against anxiety were correlated with synaptic transmission, substance addiction and retinol metabolism, especially targeted on CNR1. It suggested that the therapeutic mechanism of SZRP treating anxiety might be due to the weak action of multiple compounds on multiple pathways and biological processes.

Mounting evidence has shown that inflammation might drive Alzheimer's disease (AD) pathology and contribute to its exacerbation. Previous studies have indicated that indomethacin or atorvastatin are beneficial in treating AD; however, no significant clinical effects have been shown. Furthermore, no study has investigated the efficacy of combining these agents for treating AD. This study sought to determine the effect of a combination of indomethacin and atorvastatin in the PrP-hAβPPswe/PS1ΔE9 (APP/PS1) transgenic AD mouse model. Treatment with indomethacin and atorvastatin ameliorated impairments in spatial learning and memory, and the active avoidance response in APP/PS1 mice. Moreover, we found a suppression of Aβ plaques and decreased concentration of Aβ1-42 in the hippocampus of APP/PS1 mice following treatment. In addition, indomethacin and atorvastatin ameliorated abnormal cytokine secretion, lymphocyte subset disorder, and hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis imbalances in APP/PS1 mice. The combination of indomethacin and atorvastatin restored immune and neuroendocrine processes, attenuated pathologic changes and cognitive impairments in APP/PS1 transgenic mice, and could thus be a potential therapeutic agent for AD.

Background Alzheimer's disease (AD) is a central nervous system (CNS) disease characterized by progressive cognitive dysfunction and memory loss. Qi Fu Yin is mainly used to treat dementia, particularly AD, in the clinic, but its comprehensive mechanisms are not known. Objective In this research, we aimed to investigate the mechanisms of Qi Fu Yin in AD by network pharmacology and molecular docking. Methods First, the chemical constituents in Qi Fu Yin were obtained from five databases and classified according to their structure. Targets of chemical constituents and AD-related targets were also collected from the databases. Then, overlapping genes between Qi Fu Yin and AD were identified by intersection analysis. MetaCore was used to gather enrichment information. Combination synergy analysis was performed by Cytoscape. After ligand-receptor docking, the binding affinity was verified by ADP-Glo™ kinase assay and fluorescence resonance energy transfer (FRET) assay. Results We found 12 classes with 977 components in Qi Fu Yin. A total of 511 compounds and 577 potential target proteins in Qi Fu Yin were found to be related to AD. The pathways of Qi Fu Yin in AD included oxidative stress and immune response. There was the best binding affinity between 11 pairs of genes and compounds. Furthermore, CDK5 was inhibited by nepetin with an IC50 of 3.172 μM and kaempferol with an IC50 of 2.659 μM. Ceanothic acid and 18 beta-glycyrrhetinic acid inhibited GSK3β, and the IC50 values were 8.732 μM and 8.06 μM, respectively. Conclusion Qi Fu Yin might alleviate Tau hyperphosphorylation by nepetin, kaempferol, ceanothic acid and 18 beta-glycyrrhetinic acid.

Aging is a natural biological process associated with cognitive decline and neuroendocrine-immune system changes; the neuroendocrine-immune system plays crucial role in brain aging and neurodegeneration, and it is essential to discern beneficial attempts to delay the aging progress based on immunological aging. In this study, we have investigated the effects of Traditional Chinese Medicine (TCM)-Liuwei Dihuang decoction (LW)-and donepezil, memantine, and melatonin on cognitive decline in aging mice. The aged SAMR1 mice received oral administration of donepezil (1mg/kg), memantine (10 mg/kg), melatonin (10 mg/kg), and LW (10 g/kg) for 3 months. A shuttle box, Morris water maze, and elevated-zero maze were performed to assess cognitive function, and flowcytometry, Luminex, and radioimmunoassay were performed to measure the lymphocyte subsets, inflammatory factors, and hormones. We observed that survival days of mice was increased with melatonin and LW, the anxiety behavior was significantly improved by memantine, melatonin, and LW treatment, active avoidance responses significantly improved by LW, donepezil, and memantine, the spatial learning ability was significantly improved by donepezil, and LW and melatonin were beneficial to the spatial memory of old mice. For immune function, LW increased CD4+ and CD4+CD28+ cells and reduced TNF-α, IL-1β, and G-CSF in plasma, and it also promoted the secretion of anti-inflammatory factors IL-4, IL-5, and IL-10 by regulating the active of Th2 cells in spleen. Donepezil and memantine exerted protective effects against CD4+CD28+ cell decrease caused by aging and reduced the pro-inflammatory factors TNF-α, IL-1β, and G-CSF in plasma. Melatonin could reverse CD8+CD28+ cell imbalances and increased B cells. For endocrine factors, LW increased TSH levels in the pituitary, and melatonin increased the GH level in blood. Our findings indicated that LW improved the cognitive decline in aging mice, and this might be associated with modulation of the active T cells and HPG axis hormones as well as increasing anti-inflammatory factors. Meanwhile, donepezil and memantine have advantages in regulating adaptive immunity, melatonin has advantages in the regulation of B cells and pituitary hormones, and LW exhibits a better effect on neuroendocrine immune function compared with the others from a holistic point of view. LW might be a potential therapeutic strategy for anti-aging-related syndromes, and it can also provide a value on medication guidance about drug combinations or treatment in clinic.

The application of pumps as turbines (PAT) has been developed in several applications for energy recovery schemes. Therefore, establishing a performance correlation between pump mode and turbine mode is essential for selecting the proper machine. However, slip phenomenon is the challenges of head prediction for PAT. In this paper, the slip phenomenon of pump and PAT was revealed, and the slip factor was studied using CFD. The effect of slip on head prediction for PAT was analyzed, and a theoretical prediction model was presented considering slip factors. In order to validate the head prediction model, six centrifugal pumps with specific speed (ns) from 9 to 54.8 were tested as turbines. Results showed that the predicted head by the proposed method was in good agreement with the experimental data, and it is more accurate than Stepanoff, Alatorre-Frenk, Sharma, and Derakhshan models. This method can be applied in head prediction for low specific speed PAT ( ns

IntroductionThe aim of this study was to investigate the potential role of a microRNA panel as early diagnostic markers for Alzheimer’s disease (AD).MethodsThe differentially expressed serum microRNAs were screened with microarray among cognitively normal controls (CNC), mild cognitive impairment (MCI), and AD. QRT-PCR assay was applied to evaluate differentially expressed microRNAs with two independent cohorts including 202 participants. Logistic regression model based on microRNA panel was constructed using a training cohort and then validated using an independent cohort.ResultsFirst, four differentially expressed serum microRNAs (let-7g, miR-197, miR-126 and miR-29a) were found, which expressions were positively correlated with mini mental state examination (MMSE) score. Second, a microRNA panel with the four microRNAs demonstrated good diagnostic performance for MCI and AD with 84% and 92% accuracy. Third, when combined with MMSE score, the diagnostic performance of the microRNA panel was further improved.DiscussionBlood microRNAs are potential AD biomarkers that may lead to new diagnostic strategies.

Compared with the general centrifugal pump, the screw centrifugal pump has a spiral radial impeller and opening flow passage. The impeller inlet is a spiral blade and outlet of blade looks like to mixing-flow pump blade. Its special structure made the screw pump not only having spiral propelling effect but also having centrifugal effect, therefore the screw centrifugal pump has both the merits of screw pump and centrifugal pump. According to the structure characteristics of screw centrifugal pump, character of flow-field inside the pump and projection drawing on foundation with one-dimension, the regularity for change of pitch in the variable-pitch parametric equation group is given in this paper. And the variable-pitch parameter equation group of the screw centrifugal pump is perfected. Using the parametric equation, to segment streamline dots on axial plane for designing screw centrifugal pump blade is facilitated, which has important meaning to the CAD, numerical simulation of three-dimension flow-field and improve performances of screw centrifugal pump

The three-dimensional turbulent flow in a supercritical pump with complex double-cases based on the integral model combined with the pass-by pipes is computed and simulated by means of a parallel computer and the software FLUENT using the mathematical models (Navier-Stokes equations, RNG k-e turbulence model and boundary conditions) in Computational Fluid Dynamics (CFD), which aims at improving the pump's performance. Meanwhile, the supercritical pump's efficiency correction is emphasized according to the leakages at wear rings of impellers and at the radial clearances between pump stages; the pump's hydraulic design and improvement are briefly introduced; the effects of grid number and pass-by pipes on the computational accuracy are discussed, and the flow fields in the internal complex passages of the pump are also represented. The hydro-dynamically numerical computational results and operation testing ones of the pump, which is modified from the original one based on the primary simulation results, indicate that they are in coincidence with each other well.

The three-dimensional turbulent flow in a supercritical pump with complex double-cases based on the integral model combined with the pass-by pressure-balancing pipes is computed and simulated by means of a parallel computer and the software FLUENT using the mathematical models (Navier-Stokes equations, turbulence model and boundary conditions) in Computational Fluid Dynamics (CFD). The effects of grid number and pass-by pipes on the computational accuracy are emphasized, and the flow fields in the internal complex passages of the pump are also represented. The hydrodynamically numerical computational results and operation testing ones indicate that they are in coincidence with each other well.