Revealing the Effect of the [CoO]6 Microstructure in Pseudocapacitance by Controlled Delithium of LiCoO2.

Revealing the in-depth structure-property relationship and designing specific capacity electrodes are particularly important for supercapacitors. Despite many efforts made to tune the composition and electronic structure of cobalt oxide for pseudocapacitance, insight into the [CoO]6 octahedron from the microstructure is still insufficient. Herein, we present a tunable [CoO]6 octahedron microstructure in LiCoO2 by a chemical delithiation process. The c-strained strain of the [CoO]6 octahedron is induced to form higher valence Co ions, and the (003) crystalline layer spacing increases to allow more rapid participation of OH- in the redox reaction. Interestingly, the specific capacity of L0.75CO2 is nearly four times higher than that of LiCoO2 at 10 mA g-1. The enhanced activity originated from the asymmetric strain [CoO]6 octahedra, resulting in enhanced electronic conductivity and Co-O hybridization for accelerated redox kinetics. This finding provides new insights into the modification strategy for pseudocapacitive transition metal oxides.

Off-Design Operation and Cavitation Detection in Centrifugal Pumps Using Vibration and Motor Stator Current Analyses.

Centrifugal pumps are essential in many industrial processes. An accurate operation diagnosis of centrifugal pumps is crucial to ensure their reliable operation and extend their useful life. In real industry applications, many centrifugal pumps lack flowmeters and accurate pressure sensors, and therefore, it is not possible to determine whether the pump is operating near its best efficiency point (BEP). This paper investigates the detection of off-design operation and cavitation for centrifugal pumps with accelerometers and current sensors. To this end, a centrifugal pump was tested under off-design conditions and various levels of cavitation. A three-axis accelerometer and three Hall-effect current sensors were used to collect vibration and stator current signals simultaneously under each state. Both kinds of signals were evaluated for their effectiveness in operation diagnosis. Signal processing methods, including wavelet threshold function, variational mode decomposition (VMD), Park vector modulus transformation, and a marginal spectrum were introduced for feature extraction. Seven families of machine learning-based classification algorithms were evaluated for their performance when used for off-design and cavitation identification. The obtained results, using both types of signals, prove the effectiveness of both approaches and the advantages of combining them in achieving the most reliable operation diagnosis results for centrifugal pumps.

Conjugation with glucagon like peptide-1 enables targeted protein degradation.

Lysosome-targeting chimeras (LYTACs) have emerged as a promising technique to extend the scope of targeted protein degradation to extracellular proteins, e.g., secreted proteins and membrane-anchored proteins. However, up to now, only a small number of lysosomal targeting receptors (LTRs), such as cation-independent mannose 6-phosphate receptor (CI-M6PR) and asialoglycoprotein receptor (ASGPR), were reported to build LYTACs for degradation of extracellular proteins. Therefore, it is important to explore more functionalized ligands for the relevant LTRs to expand the LYTAC framework. Herein, we demonstrate a new LTR ligand-glucagon like peptide 1 (GLP-1) based targeted degradation platform, termed GLP-1 receptor-targeting chimeras (GLP-1-LYTAC). GLP-1-LYTACs are formed by conjugating GLP-1 with targeted binder (such as antibody) through Click Chemistry, showing efficiently lysosomal degradation of both extracellular proteins (GFP and Neutravidin) as well as cell membrane proteins (EGFR and PD-L1). We believe that this novel GLP-1-LYTAC will open up a new dimension for targeted protein breakdown.

Is it really safe to replace decabromodiphenyl ether (BDE209) with decabromodiphenyl ethane (DBDPE)?: A perspective from hepatotoxicity.

In this paper, the hepatocytotoxicity and aryl hydrocarbon receptor (AHR) activity of decabromodiphenyl ethane (DBDPE), decabromodiphenyl ether (BDE209) and other 18 analogues were evaluated in vitro using human normal liver cell L02. These dioxin-like compounds showed differential hepatocytotoxicity (EC50  = 0.38-17.87 mg/L) and AHR activity (EROD activity = 4.53-46.35 U/µg). In silico study indicated the distance of π-π bonds between the benzene ring of compounds and residue Phe234 of AHR played a key role in the binding of AHR, and the substituents on the benzene ring also influenced the activity. Combining molecular biology and bioomics, the comprehensive investigations on the hepatotoxic mechanisms have demonstrated the AHR signaling pathway was the key mediation mechanism for the hepatotoxicity of DBDPE/BDE209. The cytochrome P450s (CYP2 family) mediated formation of reactive oxygenated intermediates might be the dominant toxic mechanism, which could produce oxidative stress or cause genotoxicity. Although the experimental toxicity of DBDPE was smaller relative to BDE209, the health risk of DBDPE may be much greater than we expected, due to the high potential to form a variety of dioxin-like intermediates by microbial oxidation of ethyl group. Therefore, whether it is really safe to replace BDE209 with DBDPE is a debatable question, and more ecotoxicological and health data are needed to clarify this issue.

Microbial community composition in urban riverbank sediments: response to municipal effluents over spatial gradient.

Municipal effluents have adverse impacts on the aquatic ecosystem and especially the microbial community. This study described the compositions of sediment bacterial communities in the urban riverbank over the spatial gradient. Sediments were collected from seven sampling sites of the Macha River. The physicochemical parameters of sediment samples were determined. The bacterial communities in sediments were analyzed by 16S rRNA gene sequencing. The results showed that these sites were affected by different types of effluents, leading to regional variations in the bacterial community. The higher microbial richness and biodiversity at SM2 and SD1 sites were correlated with the levels of NH4+-N, organic matter, effective sulphur, electrical conductivity, and total dissolved solids (p < 0.01). Organic matter, total nitrogen, NH4+-N, NO3-N, pH, and effective sulphur were identified to be important drivers for bacterial community distribution. At the phylum level, Proteobacteria (32.8-71.7%) was predominant in sediments, and at the genus level, Serratia appeared at all sampling sites and accounted for the dominant genus. Sulphate-reducing bacteria, nitrifiers, and denitrifiers were detected and closely related to contaminants. This study expanded our understanding of municipal effluents on microbial communities in riverbank sediments, and also provided valuable information for further exploration of microbial community functions.

Polymer Chainmail: Steric Hindrance and Charge Compensation of Anion-Doped PEDOT to Boost Stress Deformation of Compressible Supercapacitor.

Conducting polymers with high theoretical capacitance and deformability are among the optimal candidates for compressible supercapacitor electrode materials. However, achieving both mechanical and electrochemical stabilities in a single electrode remains a great challenge. To address this issue, the "Polymer Chainmail" is proposed with reversible deformation capability and enhances stability because of the steric hindrance and charge compensation effect of doped anions. As a proof of concept, four common anions are selected as dopants for Poly(3,4-ethylenedioxythiophene) (PEDOT), and their effects on the adsorption and diffusion of H+ on PEDOT are verified using density functional theory calculations. Owing to the film formation effect, the PF 6 - ${{\rm{PF}}_6^- }$ doped PEDOT/nitrogen-doped carbon foam exhibits good mechanical properties. Furthermore, the composite demonstrates excellent rate performance and stability due to suitable anion doping. This finding provides new insights into the preparation of electrochemically stable conductive polymer-based compressible electrode materials.

Evolution and functional diversification of catalase genes in the green lineage.

BACKGROUND: Catalases (CATs) break down hydrogen peroxide into water and oxygen to prevent cellular oxidative damage, and play key roles in the development, biotic and abiotic stresses of plants. However, the evolutionary relationships of the plant CAT gene family have not been systematically reported. RESULTS: Here, we conducted genome-wide comparative, phylogenetic, and structural analyses of CAT orthologs from 29 out of 31 representative green lineage species to characterize the evolution and functional diversity of CATs. We found that CAT genes in land plants were derived from core chlorophytes and detected a lineage-specific loss of CAT genes in Fabaceae, suggesting that the CAT genes in this group possess divergent functions. All CAT genes were split into three major groups (group α, ß1, and ß2) based on the phylogeny. CAT genes were transferred from bacteria to core chlorophytes and charophytes by lateral gene transfer, and this led to the independent evolution of two types of CAT genes: α and ß types. Ten common motifs were detected in both α and ß groups, and ß CAT genes had five unique motifs, respectively. The findings of our study are inconsistent with two previous hypotheses proposing that (i) new CAT genes are acquired through intron loss and that (ii) the Cys-343 residue is highly conserved in plants. We found that new CAT genes in most higher plants were produced through intron acquisition and that the Cys-343 residue was only present in monocots, Brassicaceae and Pp_CatX7 in P. patens, which indicates the functional specificity of the CATs in these three lineages. Finally, our finding that CAT genes show high overall sequence identity but that individual CAT genes showed developmental stage and organ-specific expression patterns suggests that CAT genes have functionally diverged independently. CONCLUSIONS: Overall, our analyses of the CAT gene family provide new insights into their evolution and functional diversification in green lineage species.

Genome-wide analysis of citrus TCP transcription factors and their responses to abiotic stresses.

BACKGROUND: Citrus is one of the most important fruit crops in the world, and it is worthy to conduct more research on artificially controlling citrus plant growth and development to adapt to different cultivation patterns and environmental conditions. The plant-specific TEOSINTE BRANCHED1, CYCOLOIDEA, and PROLIFERATING CELL FACTORS (TCP) transcription factors are crucial regulators controlling plant growth and development, as well as responding to abiotic stresses. However, the information about citrus TCP transcription factors remains unclear. RESULTS: In this study, twenty putative TCP genes (CsTCPs) with the TCP domain were explored from Citrus sinensis genome, of which eleven (CsTCP3, - 4, - 5, - 6, - 10, - 11, - 15, - 16, - 18, - 19, - 20), five (CsTCP1, - 2, - 7, - 9, - 13), and four genes (CsTCP8, - 12, - 14, - 17) were unevenly distributed on chromosomes and divided into three subclades. Cis-acting element analysis indicated that most CsTCPs contained many phytohormone- and environment-responsive elements in promoter regions. All of CsTCPs were predominantly expressed in vegetative tissues or organs (stem, leaf, thorn, and bud) instead of reproductive tissues or organs (flower, fruit, and seed). Combined with collinearity analysis, CsTCP3, CsTCP9, and CsTCP13 may take part in leaf development; CsTCP12 and CsTCP14 may function in shoot branching, leaf development, or thorn development; CsTCP15 may participate in the development of stem, leaf, or thorn. In mature leaf, transcript levels of two CsTCPs (CsTCP19, - 20) were significantly increased while transcript levels of eight CsTCPs (CsTCP2, - 5, - 6, - 7, - 8, - 9, - 10, - 13) were significantly decreased by shading; except for two CsTCPs (CsTCP11, - 19), CsTCPs' transcript levels were significantly influenced by low temperature; moreover, transcript levels of two CsTCPs (CsTCP11, - 12) were significantly increased while five CsTCPs' (CsTCP14, - 16, - 18, - 19, - 20) transcript levels were significantly reduced by drought. CONCLUSIONS: This study provides significant clues for research on roles of CsTCPs in regulating citrus plant growth and development, as well as responding to abiotic stresses.

A deep-learning model for identifying fresh vertebral compression fractures on digital radiography.

OBJECTIVES: To develop a deep-learning (DL) model for identifying fresh VCFs from digital radiography (DR), with magnetic resonance imaging (MRI) as the reference standard. METHODS: Patients with lumbar VCFs were retrospectively enrolled from January 2011 to May 2020. All patients underwent DR and MRI scanning. VCFs were categorized as fresh or old according to MRI results, and the VCF grade and type were assessed. The raw DR data were sent to InferScholar Center for annotation. A DL-based prediction model was built, and its diagnostic performance was evaluated. The DeLong test was applied to assess differences in ROC curves between different models. RESULTS: A total of 1877 VCFs in 1099 patients were included in our study and randomly divided into development (n = 824 patients) and test (n = 275 patients) datasets. The ensemble model identified fresh and old VCFs, reaching an AUC of 0.80 (95% confidence interval [CI], 0.77-0.83), an accuracy of 74% (95% CI, 72-77%), a sensitivity of 80% (95% CI, 77-83%), and a specificity of 68% (95% CI, 63-72%). Lateral (AUC, 0.83) views exhibited better performance than anteroposterior views (AUC, 0.77), and the best performance among respective subgroupings was obtained for grade 3 (AUC, 0.89) and crush-type (AUC, 0.87) subgroups. CONCLUSION: The proposed DL model achieved adequate performance in identifying fresh VCFs from DR. KEY POINTS: • The ensemble deep-learning model identified fresh VCFs from DR, reaching an AUC of 0.80, an accuracy of 74%, a sensitivity of 80%, and a specificity of 68% with the reference standard of MRI. • The lateral views (AUC, 0.83) exhibited better performance than anteroposterior views (AUC, 0.77). • The grade 3 (AUC, 0.89) and crush-type (AUC, 0.87) subgroups showed the best performance among their respective subgroupings.

Transcriptomic and Metabolomic Analyses of the Effects of Exogenous Trehalose on Heat Tolerance in Wheat.

Trehalose can improve the tolerance of plants to various types of environmental stress. Nonetheless, information respecting the molecular networks of wheat seedlings to exogenous trehalose under heat stress is limited. Here, two wheat varieties pretreated with exogenous trehalose were selected to explore the molecular mechanism by which trehalose improves the heat tolerance of wheat (Triticum aestivum L.). The results indicated that exogenous trehalose improved the physiological state of wheat seedlings under heat stress. Through RNA sequencing and metabolomics analysis, the genes and metabolites specifically expressed in trehalose pretreatment were identified. After heat stress, there were 18,352 differentially expressed genes (DEGs) in the control and trehalose-treated (H_vs_TreH) groups of Yangmai 18 and 9045 DEGs in Yannong 19. Functional annotation and enrichment analyses showed that the DEGs in the two wheat varieties were mainly involved in carbohydrate metabolism and biosynthesis of secondary metabolites. Through a liquid chromatography-mass spectrometry platform, 183 differential metabolites in H_vs_TreH groups of Yangmai 18 and 77 differential metabolites in Yannong 19 were identified. Compared with the control group, many protective metabolites, such as amino acids, purines, phenylpropanoids and flavonoids, showed significant differences under heat stress. The results indicated that exogenous trehalose protected the wheat biomembrane system, enhanced carbohydrate metabolism and signal transduction, strengthened the activity of the tricarboxylic acid cycle (TCA cycle), regulated purine metabolism, gene expression and metabolite accumulation in the phenylpropanoid biosynthesis and flavonoid biosynthesis pathways, thus improving the heat tolerance of wheat.

[Comparison of Clinical Efficacy of Thermal Ablation vs. Surgical Resection of Metachronous Colorectal Liver Metastasis].

Objective: To compare the treatment efficacy of thermal ablation versus surgical resection of metachronous colorectal liver metastasis (CRLM) and to explore the potential candidates suited for thermal ablation. Methods: The data of 319 patients with CRLM who underwent radical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences between November 2007 and January 2021 were retrospectively collected. The patients were divided into two groups, the thermal ablation group and the surgical resection group, according to the actual treatments they received. Propensity score matching (PSM) was applied to balance the baseline characteristics between the two groups. Cox regression analysis was conducted to identify the risk factors for recurrence and survival. Survival analysis was performed for intergroup comparison. Results: Using PSM at 1∶1 ratio, 92 patients were included in the thermal ablation group and 92 patients were included in the surgical resection group.The median overall survival (OS) in the thermal ablation group was 49 (95% confidence interval, 37-76) months, which was shorter than that of the surgical resection group ( P<0.01). Multivariate Cox regression analysis indicated that the T staging of primary tumor, number of metastatic tumor, maximum diameter of metastatic tumor, preoperative serum carcinoembryonic antigen (CEA) level, and treatment method were independent risk factors affecting OS. Compared with the surgical resection group, the thermal ablation group demonstrated higher hepatic recurrence rate (59.8% vs. 23.9%, P<0.01), shorter disease-free survival (DFS) (10 months vs. 33 months, P<0.01), and shorter length of hospital stay (7 days vs. 14 days, P<0.01). Subgroup analysis, conducted with the data of the 319 patients before PSM, showed that early recurrence patients who underwent thermal ablation or surgical resection had comparable median OS (29 months vs. 42 months, P=0.35). For the non-early recurrence patients, the median OS of the thermal ablation group was shorter than that of the surgical resection group ( P<0.01). Conclusion: For the treatment of CRLM, the efficacy of surgical resection was better than that of thermal ablation. However, the efficacy was comparable between the two treatments for early recurrence patients of CRLM.

Signaling pathways of EBV-induced oncogenesis.

Epstein-Barr virus (EBV) is closely associated with multiple human cancers. EBV-associated cancers are mainly lymphomas derived from B cells and T cells (Hodgkin lymphoma, Burkitt lymphoma, NK/T-cell lymphoma, and posttransplant lymphoproliferative disorder (PTLD)) and carcinomas derived from epithelial cells (nasopharyngeal carcinoma and gastric carcinoma). EBV can induce oncogenesis in its host cell by activating various signaling pathways, such as nuclear factor-κB (NF-κB), phosphoinositide-3-kinase/protein kinase B (PI3K/AKT), Janus kinase/signal transducer and transcription activator (JAK/STAT), mitogen-activated protein kinase (MAPK), transforming growth factor-ß (TGF-ß), and Wnt/ß-catenin, which are regulated by EBV-encoded proteins and noncoding RNA. In this review, we focus on the oncogenic roles of EBV that are mediated through the aforementioned signaling pathways.

The Efficacy and Safety of Epicutaneous Immunotherapy for Allergic Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically review the effect and safety of epicutaneous immunotherapy (EPIT) for allergic diseases. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, CQ VIP Database, Wanfang Data, and international trial register from their inception to July 29, 2019, without language restrictions, for randomized controlled trials (RCTs) that compared EPIT versus no EPIT for allergen-triggered allergic reactions. We assessed certainty of evidence by the GRADE approach. RESULTS: Ten RCTs with 1,085 participants (aged from 10 months to 65 years) comparing EPIT with placebo for peanut, cow milk, or grass-pollen allergy met the eligibility criteria. A substantial benefit in terms of desensitization in EPIT group was more likely for peanut or cow milk protein allergy (risk ratio [RR] 2.34, 95% CI 1.69-3.23; I2 = 0%; high certainty evidence). EPIT increased local-treatment-related adverse events (L-TRAE; RR 1.56, 95% CI 1.03-2.36; I2 = 82%; moderate certainty evidence). But there were no significantly increased risk of any TRAEs (low certainty evidence) or systemic-TRAEs (S-TRAEs; very low certainty evidence) in EPIT group. The incidence rate of serious AEs, the use of rescue medications, and anaphylactic reactions stratified by organ systems including skin and mucosa, eyes and upper respiratory, lower respiratory, and gastrointestinal system in EPIT group were similar to placebo group. In subgroup analysis, desensitization of EPIT was significantly effective in peanut allergy (RR 2.29, 95% CI 1.64-3.21; I2 = 0%) and children <12 years (RR 2.85, 95% CI 1.92-4.24; I2 = 0%) with high certainty evidence. Only epicutaneous grass-pollen immunotherapy significantly increased the risk of S-TRAE (RR 4.65, 95% CI 1.10-19.64; I2 = 0%). CONCLUSION: The systematic review suggests that EPIT might induce desensitization in peanut allergy and an increased risk of local AEs. These findings should be interpreted with caution owing to the limited study and heterogeneity. More data in the older (children ≥12 years and adults) and other allergic diseases are needed.

The development and understanding of intracranial aneurysm based on rabbit model.

In modern society, intracranial aneurysms have seriously affected people's life. To better study and treat intracranial aneurysm, animal models are ideal candidates to perform biological research and preclinical endovascular device testing. Rabbit aneurysm model is one of the most commonly used animal models, and the rabbit aneurysms share similarities in histology, morphology, and hemodynamic aspects with human intracranial aneurysms, which is an ideal model for intracranial aneurysm pre-clinical and basic research. In this review, we will summarize the main methods of establishing rabbit aneurysms model and will further discuss the current biological mechanisms of intracranial aneurysms based on rabbit model. Further improvements of rabbit aneurysm model and more deep studies based on this model are needed to provide new insights into studying and clinical treating intracranial aneurysm.

Research on the Single-Value Indicators for Centrifugal Pump Based on Vibration Signals.

Off-design operation conditions might not only seriously affect the internal flow status of a centrifugal pump, but also result in additional energy loss and potential mechanical damage. Therefore, early-stage monitoring and predication on off-design operation conditions for centrifugal pumps have become essential. Single-value indicators have favorable factors such as a smaller amount of calculation and easier identification. As a result, industries prefer the more straightforward approach: obtaining single-value indicators directly from the signals which could be easier compared with accepted standards. The possibility of applying the single-value indicators of vibration into operation condition monitoring for a centrifugal pump is studied theoretically and experimentally, which shows that the statistical features of vibration might be suitable for hydraulic instability detection for a centrifugal pump.

After-effects of repetitive anodal transcranial direct current stimulation on learning and memory in a rat model of Alzheimer's disease.

Repetitive anodal transcranial direct current stimulation (tDCS) in a rat model of Alzheimer's disease (AD) has been shown to have distinct neuroprotective effects. Moreover, the effects of anodal tDCS not only occur during the stimulation but also persist after the stimulation has ended (after-effects). Here, the duration of the after-effects induced by repetitive anodal tDCS was investigated based on our previous studies. Adult male Sprague-Dawley rats were divided into three groups: a sham group, a ß-amyloid (Aß) group (AD group) and a stimulation group (ATD group). Aß was injected into the bilateral hippocampi of the rats in the AD and ATD groups to produce the AD model. Rats in the ATD group underwent 10 sessions of anodal tDCS, and the after-effects of repetitive anodal tDCS were evaluated by behavioral and histological analyses. A Morris water maze (MWM) was utilized on a monthly basis to assess spatial learning and memory abilities. The ATD group showed shorter escape latencies and more platform region crossings than the AD group. Hippocampal choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) immunohistochemical analyses were carried out after the last MWM assessment. The immunohistochemistry results showed notable differences among the groups, particularly between the AD and ATD groups. This study reveals that repetitive anodal tDCS can not only improve cognitive function and memory performance but also has long-term after-effects that persist for 2 months.

[Anti-inflammatory mechanism of Xixian Tongshuan Preparation based on molecular simulation methods].

Inflammatory response is caused by exogenous and endogenous stimuli,resulting in a non-specific resistance reaction.After acute ischemic cerebral infarction,inflammatory factors gather and adhere in the ischemic area of leukocyte infiltration,and the released inflammatory factors causes the injury cascade,aggravate the brain tissue damage and the symptoms of neurological deficits,and hinder the repair of brain neurons and the recovery of nerve function. In this paper,the key targets in the arachidonic acid metabolic pathway were studied. The Hiphop pharmacophore model of s PLA2-ⅡA and COX-2 inhibitors was built. According tothe two previously constructed 5-LOX and LTA4 H target inhibitors,the pharmacophore model was used to initially screen out the composition database of all of 13 traditional Chinese medicines in Xixian Tongshuan Preparation. The molecular matching study was carried out by selecting the matching value greater than 0. 6,and the component with the CDOCKER score greater than 80% of the original ligand score was used as the potential active inhibitor of the target. Considering the pharmacophore matching value,the molecular docking score and the interaction between the components and the target,one Chuanxiong component and one safflower component were selected as potential inhibitors of s PLA2-ⅡA; two Chuanxiong components,two Panax notoginseng,one safflower component,one angelica component,one valerian component were taken as a potential inhibitor of COX-2; two Gentiana components,one safflower component,one valerian component,one P. notoginseng component and one Angelica component were taken as potential inhibitors of 5-LOX; and two Gentiana components,two Chuanxiong components,and two safflower components were taken as potential inhibitors of LTA4 H. This study screened out the potential inhibitors of the four targets in a high-efficiency and low-cost manner,and explained that Xixian Tongshuan Preparation showed an effect in the treatment of inflammatory responses caused by ischemic stroke by acting both LOX pathway and COX pathway in the metabolic pathway.

[Lipid regulation mechanism and dosage form selection of Xixian Tongshuan Preparation based on molecular simulation methods].

Atherosclerosis is the main cause of stroke, and dyslipidemia is the most important risk factor for atherosclerosis. In this paper, pharmacophore and molecular docking models of eight key lipid-lowering targets, namely NPC1 L1, HMG-CoA reductase, SQS, MTP, CETP, PPARα, LXRα and LXRß, were used to screen out the small molecular database of traditional Chinese medicine(TCM), which was made up of ingredients of thirteen Chinese herbal medicines contained in Xixian Tongshuan Preparation. The screening results indicated that the preparation could showed an effect in regulating lipid on target NPC1 L1, HMG-CoA reductase, LXRß and SQS through four groups of potential active compounds, namely prupersin A in peach kernel and suffruticoside A in gastrodiaelata, limocitrin-ß-D-glucoside in Ligusticum chuanxiong, 2'-(2,3-dihydroxybenzoyl)-sweroside in Pinellia ternate and quercitrin in Panax notoginseng, 4-tert-butyl-2-[(5-tert-butyl-2-hydroxy-phenyl)methoxy-methyl]-6-(hydroxymethyl)phenol in Gastrodia elata. Moreover, the properties and extraction process of the most potentialactive compounds were consistent with the preparation process of Xixian Tongshuan Capsules, which indicated that the capsule had more advantages than the pill in the existing two dosage forms of Xixian Tongshuan Preparation. This study analyzed the pharmacodynamic basis and mechanism of Xixian Tongshuan Capsules in regulating lipid for treating stroke, and provided evidence for its further research and clinical application.

[Multi-target neuroprotective effect of Xixian Tongshuan Preparation against cerebral ischemia injury].

In this paper, Xixian Tongshuan Preparation was used as the research object, and all the chemical components of the 13 traditional Chinese medicines were collected. The target finding technique was used to obtain the key targets of the neuroprotective effect of Xixian Tongshuan Preparation, including 5 glutamate receptors, TGFR-1 and VEGFR-2. Molecular docking technology was used to screen out the potential active components of the above targets and to analyze their mechanism of action. It was found that single component, such as neo-complanatoside and neo-carthamin, in Xixian Tongshuan Preparation could simultaneously act on different targets. The chemical constituents in Ligusticum chuanxiong, Angelica sinensis, Carthamus tinctorius, and Panax pseudo-ginseng could simultaneously act on different neuroprotective-related targets, which reflected the application of multi-components to multi-targets. Point and multiple sites played a key role in protecting neurons against cerebral ischemic injury. This study explains the multi-target mechanism of anti-cerebral ischemic injury in neuroprotection at the molecular level, and provides a certain direction for the clinical application and experimental research of Xixian Tongshuan Preparation.

[Anti-platelet aggregation mechanism of Xixian Tongshuan Preparation based on molecular simulation methods].

The thrombus is a deposit that is formed on the surface of the endovascular or at the site of repair,and known as the main complication of cardiovascular disease and the cause of death. At the same time,thrombus is mainly treated by the following three ways: anticoagulation,anti-platelet aggregation and thrombolysis. In this study,the chemical constituents of seven traditional Chinese medicines in the Xixian Tongshuan Preparation were collected to construct a component database. Subsequently,the pharmacophore were used to screen out the component database,and molecular docking was used to screen out the results of pharmacophore for explaining the material basis and mechanism that Xixian Tongshuan Preparation exerts anti-thrombotic activity by inhibiting platelet aggregation. First of all,P2 Y12,GPⅡb/Ⅲa and PAR1 were selected as study vectors,the optimal models of inhibitors were obtained respectively through verification and evaluation of the pharmacophore models. Afterwards,the component database was screened out by the optimal pharmacophore models of PAR1,P2 Y12 and GP Ⅱ b/Ⅲ a,and the molecular docking method was used to further refine the screening results. The screening results indicated that the anti-platelet aggregation effect of Xixian Tongshuan Preparation was correlated with the inhibition of P2 Y12,PAR1 and GPⅡb/Ⅲa expressions with saffower yellower,hirudin and candidin and notoginseng triterpenes,folinic acid,respectively. The material basis and mechanism of anti-platelet aggregation of Xixian Tongshuan Preparation provided a theoretical basis for the clinical use of the preparation and the lead compounds for the development of anti-platelet aggregation drugs.