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Purpose: The spinal nerve ligation (SNL) model is a typical peripheral neuropathic pain model. During its construction, the removal of paraspinal muscles and transverse processes typically occurs, resulting in additional trauma that may potentially affect the pathophysiologic process of neuropathic pain. This study aimed to investigate the feasibility of establishing a more reliable SNL model using an oblique lateral approach. Methods: 36 adult male Sprague-Dawley rats were randomly divided into three groups: the traditional SNL (T-SNL) group, the new SNL (N-SNL) group (where the left L5 spinal nerve was ligated with a titanium clip via an oblique lateral approach), and the sham-operated (Sham) group. The operation time, Intraoperative bleeding, the number of rats that died, gait behavior, mechanical and cold pain threshold were recorded and measured. Stereology technology was used to calculate the number of microglia in spinal dorsal horn, and the Enzyme-linked immunosorbent assay (ELISA) technology was used to detect the expression of TNF-α and IL-1β in spinal cord as well as C-reactive protein (CRP) in serum in order to assess the effect of surgery on animal inflammation. Results: Compared with the T-SNL group, operative time and intraoperative bleeding were significantly decreased in the N-SNL group. Within 14 days postoperation, one rat in the N-SNL group was died, two rats in the T-SNL group were died. Compared with the Sham group, the N-SNL group showed obvious spontaneous pain behavior, decreased the pain thresholds, the number of microglia and the expression of TNF-α and IL-1β were significantly increased, and there was no significant difference in these indexes compared with T-SNL group. There was no significant difference in serum CRP levels among the three groups. Conclusion: This study suggests that the oblique lateral approach SNL model is a reliable NP model with the advantages of good reproducibility, accessibility, and low trauma. [ABSTRACT FROM AUTHOR]

Optimizing the allocation of preschool education resources and improving the efficiency of resource allocation is of great strategic significance for the universal and inclusive development of preschool education and the realization of "education for young children". In recent years, the shift from high-speed development to high-quality development of the social economy has significantly improved the balanced development level of China's preschool education industry. However, preschool education remains the weakest link in China's education system and the most unfavorable aspect of educational resource allocation. Problems such as shortage of preschool education resources, insufficient investment, uneven regional development, imbalanced supply and demand structure, low resource allocation efficiency, and "difficult to enter, expensive to enter" are still prominent. How to optimize resource allocation and improve resource utilization efficiency in the limited resources of preschool education is the key to achieving balanced, fair, coordinated, and high-quality development of preschool education. The county preschool education resource allocation level evaluation is MAGDM problems. Recently, the TODIM and TOPSIS technique was employed to cope with MAGDM issues. The interval-valued Pythagorean fuzzy sets (IVPFSs) are employed as a tool for characterizing uncertain information during the county preschool education resource allocation level evaluation. In this manuscript, the interval-valued Pythagorean fuzzy TODIM-TOPSIS (IVPF-TODIM-TOPSIS) technique is built to solve the MAGDM under IVPFSs. Finally, a numerical case study for county preschool education resource allocation level evaluation is given to validate the proposed technique. The main contribution of this paper is managed: (1) the TODIM and TOPSIS technique was extended to IVPFSs; (2) Information Entropy is employed to manage the weight values under IVPFSs. (3) the IVPF-TODIM-TOPSIS technique is founded to manage the MAGDM under IVPFSs; (4) Algorithm analysis for county preschool education resource allocation level evaluation and comparison analysis are constructed based on one numerical example to verify the feasibility and effectiveness of the IVPF-TODIM-TOPSIS technique. [ABSTRACT FROM AUTHOR]

Euphorbia factor L1 (EFL1, 1) is a natural tri-ester of 6,17-epoxylathyrol with cancer multidrug resistance (MDR) reversal activity. Several EFL1 derivatives (2–9) were prepared by chemical and microbial transformations and their ability to inhibit P-glycoprotein (P-gp) activity was estimated. Six de-acylated derivatives (2–7) were obtained through base-hydrolysis of 1, and the base-catalysed hydrolysis via KOH and NaOH yielded different hydrolysed products of 1. Two biotransformed products (8–9) were directly obtained via microbial transformation of 1, and 8 was also formed by microbial conversion of the hydrolysed product 3. The P-gp modulation of 1–9 was assessed by a zebrafish model. The substrate 1 and its biotransformed product 9 as the tri-esters of lathyranes possessed the highest P-gp inhibitory activity with IC50 values of 34.97 and 15.50 µM, respectively, through down-regulating P-gp expression at the protein level rather than at MDR1 mRNA level. [ABSTRACT FROM AUTHOR]

This paper focuses on configuration design, dimensional synthesis, and engineering application of a novel asymmetric 2R1T parallel mechanism (PM) with zero-coupling degree. The analytical forward and inverse displacement solutions are deduced by the means of vector method. The mathematical models between Euler angles and the orientational parameters (i.e., azimuth and tilt angles) of the offset output axis are established. Using screw theory as mathematical tool, this paper worked out evaluation indices of motion/force transmissibility and presented the definitions and calculation methods of good transmission orientation workspace and good transmission orientation capacity (GTOC). Furthermore, a comparative example with respect to kinematic performance of asymmetric UPS-RPU-PU PM and planar symmetric 2UPS-PU PM is carried out, and the result demonstrates that UPS-RPU-PU significantly outperforms 2UPS-PU in terms of GTOC. The constrained optimization model is constructed to formulate optimal problem of dimensional parameters on the maximizing GTOC, which is then solved by differential evolution algorithm. Finally, an engineering case demonstrates that the optimized mechanism has a good application prospect in hydraulic support test bed. [ABSTRACT FROM AUTHOR]

Using a hedging strategy to stabilize fuel price is very important for airline companies in order to reduce the cost of their main business. In this paper, we construct models for managing the risk of the hedging strategy. First, we use conditional value at risk (CVaR) to measure the risk of an airline company's hedging strategy. Compared with the value at risk (VaR), CVaR satisfies subadditivity, positive homogeneity, monotonicity, and transfer invariance. Therefore, CVaR is a consistent method of risk measurement. Second, time-varying state transition probability is introduced into our model in order to build a Markov Switching-GARCH (MS-GARCH). MS-GARCH takes dynamic changes of market state into account, a feature which has obvious advantages over the traditional constant state model. Additionally, we use a Markov chain Monte Carlo (MCMC) algorithm to estimate the parameters of MS-GARCH based on Gibbs sampling. We use fuel oil futures data from the Shanghai Futures Stock Exchange to implement and evaluate our model. In this paper, we empirically estimate the risk of airlines' hedging strategy and draw the conclusion that our model is obviously effective in terms of the risk management of hedging, a use which has a certain guiding significance for reality. [ABSTRACT FROM AUTHOR]

Copyright of CyTA: Journal of Food is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose. Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated. This study aims to investigate the mechanism of action of curcumin in the treatment of CRC via bioinformatics methods such as network pharmacology and molecular docking. Methods. The targets of curcumin and CRC were obtained from the public databases. The component-targets network of curcumin in the treatment of CRC was constructed by Cytoscape v3.7.2. Through protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), important targets and signaling pathways related to CRC treatment were identified. Finally, the results were verified by molecular docking, and the correlation between the key targets and tumor-infiltrating immune cells (TICs) was analyzed. Results. A total of 30 potential targets of curcumin for CRC treatment were collected. The GO function enrichment analysis showed 140 items, and the KEGG pathway enrichment analysis showed 61 signaling pathways related to the regulation of protein kinase activity, negative regulation of apoptosis process, cancer signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results showed that curcumin could be combined with AKT1, EGFR, and STAT3 more stably, and AKT1 has the strongest binding to curcumin. Bioinformatics analysis discovered that the expression of core targets AKT1, EGFR, and STAT3 in CRC was related to TICs. Conclusion. This study explored the targets and pathways of curcumin in the treatment of CRC. The core targets are AKT1, EGFR, and STAT3. The study indicated that curcumin has preventive and treatment effects on CRC through multitarget and multipathway, which laid the foundation for follow-up research. [ABSTRACT FROM AUTHOR]

Melatonin has been proposed as a potent anticarcinogen presents a short half-life for osteosarcoma (OS). Cell-in-cell (CIC) structures play a role in the development of malignant tumors by changing the tumor cell energy metabolism. This study developed a melatonin-loaded 3D printed magnesium–polycaprolactone (Mg–PCL) scaffold and investigated its effect and molecular mechanism on CIC in OS. Mg–PCL scaffold was prepared by 3D-printing and its characteristic was determined. The effect and molecular mechanism of Mg–PCL scaffold as well as melatonin-loaded Mg–PCL on OS growth and progression were investigated in vivo and in vitro. We found that melatonin receptor 1 (MT1) and CIC expressions were increased in OS tissues and cells. Melatonin treatment inhibit the key CIC pathway, Rho/ROCK, through the cAMP/PKA signaling pathway, interfering with the mitochondrial physiology of OS cells, and thus playing an anti-invasion and anti-metastasis role in OS. The Mg–PCL–MT could significantly inhibit distant organ metastasis of OS in the in vivo model. Our results showed that melatonin-loaded Mg–PCL scaffolds inhibited the proliferation, invasion and metastasis of OS cells through the CIC pathway. The Mg–PCL–MT could be a potential therapeutics for OS. [ABSTRACT FROM AUTHOR]

Objective: To screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology. Methods: The molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD. Results: The general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis. Conclusion: The pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level. [ABSTRACT FROM AUTHOR]

Two new thiophene derivatives (1 and 2), a new sesquiterpene (3), and 15 known compounds (4–18) were isolated from the whole plants of Artemisia rupestris. The new compounds (1–3) were elucidated by extensive spectroscopic techniques including 1 D (1H and 13C) and 2 D NMR experiments (COSY, HSQC, HMBC and NOESY), and HR-ESI-MS. Most of the isolates (1–6, 8, 10–18) exhibited the neuraminidase inhibitory activity with IC50 values ranging from 74.07–986.54 μM by a fluorescence-based assay. Two known flavonoids (chrysosplenetin B and luteolin) showed a comparable activity to oseltamivir acid on neuraminidase inhibition. [ABSTRACT FROM AUTHOR]

Introduction: Dragendorff's reagent has low sensitivity and non‐specificity for some alkaloids. A new alkaloid derivatisation reagent has been developed and optimised by using a Box–Behnken design method. This new reagent is applicable for structurally diverse natural alkaloids, and is proposed as a universal alkaloid staining reagent. Objective: To establish an efficient and sensitive thin‐layer chromatography (TLC) identification method for Leonuri Herba and Leonuri Fructus to characterise their differences and similarities. Method: Three key components (bismuth subnitrate, potassium iodide and iodine) in the derivatisation reaction were re‐constructed and optimised using a response surface method. Different inorganic acids, essential additives of the staining reaction, were compared by a single‐factor experiment design. Results: This newly optimised reagent for alkaloids reported in this study, named the enhanced Dragendorff–Wagner's reagent, is composed of 0.82% bismuth subnitrate, 11.1% potassium iodide and 0.76% iodine in 38% phosphoric acid solution. Validation results indicate that the TLC spot of stachydrine stained with the enhanced Dragendorff–Wagner's reagent had a limit of detection of 2.0 μg, good intra‐ and inter‐plate, and intra‐ and intra‐day precisions with relative standard devition values less than 5.0%, and stability over 90 min. Conclusion: This enhanced Dragendorff–Wagner's reagent was applied for TLC identification of 16 reference alkaloids representing 11 structural skeletons, and two closely related herbs (Leonuri Herba and Leonuri Fructus). This newly enhanced Dragendorff–Wagner's reagent is a universal, effective, and sensitive staining reagent for alkaloids. A new derivatization reagent for TLC analysis of alkaloids, named enhanced Dragendorff‐Wagner's reagent, was re‐constructed and optimized. This enhanced Dragendorff‐Wagner's reagent was successfully applied for TLC identification of two closely related herbs (Leonuri Herba and Leonuri Fructus). This universal derivatization reagent was found to positive detection for 16 reference alkaloids representing 11 structural skeletons. [ABSTRACT FROM AUTHOR]

Introduction: Glucosinolates (1–5) are important secondary metabolites found in Isatis indigotica roots. Due to their high hydrophilic and ionic nature, purified glucosinolates often contain salt impurities and moisture. Accurate assessment of their purities is important for glucosinolates being utilised as chemical markers. Objective: To develop and validate quantitative proton (1H) nuclear magnetic resonance (qHNMR) methods for purity assessments of aliphatic and indole glucosinolates (1–5). Method: Several NMR parameters such as pulse program, relaxation time, and delay time were optimised. Three qHNMR methods were developed using gluconapin (3), neoglucobrassicin (4), and sinigrin (5) for method validation and with maleic acid as internal standard. Results: The quantification was based on the integrated area ratios of an olefinic proton (H‐4 for 1–3; H‐6 for 4; and H‐3 for 5) of the side chain from glucosinolates relative to the olefinic proton from the internal standard using deuterated water (D2O) as the solvent. The qHNMR methods were successfully applied for purity assessments of four aliphatic glucosinolates (1–3 and 5: progoitrin, epiprogoitrin, gluconapin, and sinigrin), and an indole glucosinolate (4: neoglucobrassicin). Conclusion: The purity of glucosinolates isolated from I. indigotica and commercial sinigrin was accurately assessed using the developed qHNMR method. The qHNMR provides a reliable and superior means to determine the purity of glucosinolates. Three qHNMR methods were developed and validated for purity assessment of aliphatic and indole glucosinolates using maleic acid as internal standard. The quantification was based on integrated area ratios of an olefinic proton of the side chain from glucosinolates relative to the olefinic proton from internal standard. The qHNMR method is a simple, rapid, irreplaceable, and accurate approach for purity assessments of glucosinolates. [ABSTRACT FROM AUTHOR]

A lismatis Rhizoma (zexie), an herb used in traditional Chinese medicine, exhibits hypolipemic, anti-inflammation and anti-atherosclerotic activities. Alisol A is one of the main active ingredients in Alismatis Rhizoma extract. In this study, we investigate the role of alisol A in anti-atherosclerosis (AS). Our study demonstrated that alisol A can effectively inhibit the formation of arterial plaques and blocked the progression of AS in ApoE−/− mice fed with high-fat diet and significantly reduced the expression of inflammatory cytokins in aorta, including ICAM-1, IL-6, and MMP-9. In addition, we found that alisol A increased the expression of PPARα and PPARδ proteins in HepG2 cells and in liver tissue from ApoE−/− mice. Alisol A activated the AMPK/SIRT1 signaling pathway and NF-κB inhibitor IκBα in HepG2 cells. Our results suggested that alisol A is a multi-targeted agent that exerts anti-atherosclerotic action by regulating lipid metabolism and inhibiting inflammatory cytokine production. Therefore, alisol could be a promising lead compound to develop drugs for the treatment of AS. [ABSTRACT FROM AUTHOR]

Four main glucosinolates (progoitrin, epiprogoitrin, gluconapin, and neoglucobrassicin) were isolated and identified from Isatis indigotica roots (Isatidis Radix). Among these, neoglucobrassicin was the first indole glucosinolate isolated from this herb, and its structure was elucidated by NMR, MS, and X-ray diffraction analysis. The glucosinolate components of Isatidis Radix have been profiled by combined use of a conventional preparative column chromatography method and a new UHPLC-QTOF-MS/MS method, and validated by simultaneous analysis of intact and desulfurized GLS. A total of 16 glucosinolates (GLS) including 12 aliphatic GLS, two aromatic GLS, and two indole GLS were identified on the basis of their UV profiles, MS/MS data, and/or by comparison with reference substances. Among these nine GLS were reported from I. indigotica for the first time. The total GLS, four isolated GLS, and (R,S)-goitrin (a degraded product of progoitrin and epiprogoitrin) have been estimated in vitro for anti-influenza viral, anti-bacterial, and anti-inflammatory activities. All the glucosinolate samples were inactive against H3N2 virus and four pathogenic bacteria, and two previously unnoticed GLS (gluconapin and neoglucobrassicin) showed significantly anti-inflammatory activity against the respiratory burst of mouse macrophages. [ABSTRACT FROM AUTHOR]

A new triterpenoid glycoside (1) and 15 known compounds (2-16) were isolated from the whole plants of Gueldenstaedtia verna. The new compound (1) was identified as complogenin 22-O-β-d-glucopyranoside by extensive spectroscopic techniques including 1D (1H and 13C) and 2D NMR experiments (HSQC, HMBC and NOESY), HR-DART-MS and chemical methods. Most of the isolates were evaluated for their inhibitory activities on LPS-induced NO production in RAW 264.7 cells. The inhibitory effects of the active compounds, sulphuretin (8) and (22E,24S)-5α,8α-epidioxy-24-methyl-cholesta-6,9(11),22-trien-3β-ol (13), on the production of pro-inflammatory mediators (including IL-6, IL1β and PGE2) were further estimated in vitro by ELISA in RAW 264.7 macrophages. [ABSTRACT FROM AUTHOR]

Introduction TLC bioautography for tyrosinase inhibitors has made recent progress; however, an assay with a relative low consumption of enzyme and quantitative capability would greatly advance the efficacy of related TLC bioautographic assays. Objective An improved TLC bioautographic assay for detecting tyrosinase inhibitors was developed and validated in this study. Methods L-DOPA (better water-solubility than L-tyrosine) was used as the substrate instead of reported L-tyrosine. The effects of enzyme and substrate concentrations, reaction temperatures and times, and pH values of the reaction system as well as different plate types on the TLC bioautographic assay were optimised. The quantitative analysis was conducted by densitometric scanning of spot areas, and expressed as the relative tyrosinase inhibitory capacity (RTIC) using a positive control (kojic acid) equivalent. Results The limit of detection (LOD) of this assay was 1.0 ng for kojic acid. This assay has acceptable accuracy (101.73-102.90%), intra- and inter-day, and intra- and inter-plate precisions [relative standard deviation (RSD), less than 7.0%], and ruggedness (RSD, less than 3.5%). The consumption of enzyme (75 U/mL) is relatively low. Two tyrosinase inhibitory compounds including naringenin and 1- O-β- D-glucopyranosyl-4-allylbenzene have been isolated from Rhodiola sacra guided by this TLC bioautographic assay. Conclusion Our improved assay is a relatively low-cost, sensitive, and quantitative method compared to the reported TLC bioautographic assays. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aiming to control rising medical expenditures and help improve China's healthcare systems, this study examined whether a cap-based medical insurance scheme with shared financial interest between the insurance and healthcare providers is effective in containing hospitals' C-section medical expenditures. We used 6547 caesarean delivery case records from a teaching tertiary-level general public hospital located in Wuxi, China (2004-2013), and used the Chow test to investigate the possibility of significant variation in mean medical expenditures for caesarean deliveries pre- and post-reform. We also used paired sample t-tests and linear regression models to compare the mean medical expenditures between insured and uninsured women undergoing caesarean delivery during the post-reform period. After the scheme's implementation, medical expenditures for caesarean deliveries declined and the medical expenditures of women covered by the scheme were significantly lower than those of uninsured patients. These findings indicated the scheme's effectiveness in minimizing caesarean delivery expenditures. The cap-based medical insurance scheme with shared financial interest between insurance and healthcare providers would likely steer healthcare providers' behaviors in a more cost-effective direction. [ABSTRACT FROM AUTHOR]

Introduction The needle trap device (NTD) technique is a new microextraction method for sampling and preconcentration of volatile organic compounds (VOCs). Previous NTD studies predominantly focused on analysis of environmental volatile compounds in the gaseous and liquid phases. Little work has been done on its potential application in biological samples and no work has been reported on analysis of bioactive compounds in essential oils from herbal medicines. Objective The main purpose of the present study is to develop a NTD sampling method for profiling VOCs in biological samples using herbal medicines as a case study. Methodology A combined method of NTD sample preparation and gas chromatography-mass spectrometry was developed for qualitative analysis of VOCs in Viola tianschanica. A 22-gauge stainless steel, triple-bed needle packed with Tenax, Carbopack X and Carboxen 1000 sorbents was used for analysis of VOCs in the herb. Furthermore, different parameters affecting the extraction efficiency and capacity were studied. Results The peak capacity obtained by NTDs was 104, more efficient than those of the static headspace (46) and hydrodistillation (93). This NTD method shows potential to trap a wide range of VOCs including the lower and higher volatile components, while the static headspace and hydrodistillation only detects lower volatile components, and semi-volatile and higher volatile components, respectively. Conclusion The developed NTD sample preparation method is a more rapid, simpler, convenient, and sensitive extraction/desorption technique for analysis of VOCs in herbal medicines than the conventional methods such as static headspace and hydrodistillation. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Context: Viola tianshanicaMaxim. (Violaceae) is a perennial herb distributed in Central Asia, especially in the Xinjiang Uygur Autonomous Region (XUAR) of China. Preliminary study showed that the ethanol extract of the herb exhibited the anti-complement activity against the classical pathway, but the active components responsible for this capacity remain unknown and are yet to be studied. Objective: The objective of this study was the isolation and identification of the anti-complement constituents ofV. tianshanica. Materials and methods: The ethyl acetate andn-butanol fractions from the ethanol extract ofV. tianshanicawere purified. The structures of the isolates were identified by spectroscopic methods, and comparing their spectral data with those reported in the literature. All the isolates (0.02–2.50 mg/mL) were evaluated for their anti-complement activity against the classical and alternative pathways. Results: Twenty-one phenolic compounds including 15 flavonolO-glycosides (1–15), one flavone 6,8-di-C-glycoside (16), one flavone aglycone (17), and four phenolic acid derivatives (18–21) were isolated and identified. Bioassay showed that 11 compounds inhibited the classical pathway and the alternative pathway with CH50and AP50values of 0.113–1.210 mM and 0.120–1.579 mM, respectively. Preliminary mechanistic study using complement-depleted sera demonstrated that1acted on C1q, C2, C4, and C9 components,16on C1q, C4, and C5, and21on C1q, C3, C4, and C9. Conclusion: All isolated compounds except1and10were reported for the first time fromV. tianshanica. Compound16is the first flavoneC-glycoside isolated from the herb. FlavonolO-glycosides and phenolic acids contributed the anti-complement activity of the herb. [ABSTRACT FROM AUTHOR]

Introduction – Lipase inhibitory assays based on TLC bioautography have made recent progress; however, an assay with greater substrate specificity and quantitative capabilities would advance the efficacy of this particular bioassay. Objective – To address these limitations, a new TLC bioautographic assay for detecting lipase inhibitors was developed and validated in this study. Methods – The new TLC bioautographic assay was based on reaction of lipase with β-naphthylmyristate and the subsequent formation of the purple dye between β-naphthol and Fast Blue B salt (FBB). The relative lipase inhibitory capacity (RLIC) was determined by a TLC densitometry with fluorescence detection, expressed as orlistat equivalents in millimoles on a per sample weight basis. Six pure compounds and three natural extracts were evaluated for their potential lipase inhibitory activities by this TLC bioautographic assay. Results – The β-naphthyl myristate as the substrate improved the detection sensitivity and specificity significantly. The limit of detection (LOD) of this assay was 0.01ng for orlistat, the current treatment for obesity. This assay has acceptable accuracy (92.07–105.39%), intra-day and inter-day precisions [relative standard deviation (RSD), 2.64–4.40%], as well as intra-plate and inter-plate precisions (RSD, 1.8–4.9%). Conclusion – The developed method is rapid, simple, stable, and specific for screening and estimation of the potential lipase inhibitors. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses a study focusing on understanding the structural basis of the Norrin-Frizzled 4 interaction. Topics discussed include proposal of the crystal structure of the extracellular cysteine-rich domain CRD of Frizzled 4 for understand how Fz4 recognizes Norrin and Wnt8, mediation of the interaction through hydrophobic interactions with a lipid molecule and specific protein-protein interactions and poor solubility of Wnt proteins due to their essential lipid modifications.

The mass spectrometric (MS) analysis of flavone di- C-glycosides has been a difficult task due to pure standards being unavailable commercially and to that the reported relative intensities of some diagnostic ions varied with MS instruments. In this study, five flavone di- C-glycoside standards from Viola yedoensis have been systematically studied by high performance liquid chromatography-electrospray ionization-tandem ion trap mass spectrometry (HPLC-ESI-IT-MSn) in the negative ion mode to analyze their fragmentation patterns. A new MS2 and MS3 hierarchical fragmentation for the identification of the sugar nature (hexoses or pentoses) at C-6 and C-8 is presented based on previously established rules of fragmentation. Here, for the first time, we report that the MS2 and MS3 structure-diagnostic fragments about the glycosylation types and positions are highly dependent on the configuration of the sugars at C-6 and C-8. The base peak (0,2X10,2X2− ion) in MS3 spectra of di- C-glycosides could be used as a diagnostic ion for flavone aglycones. These newly proposed fragmentation behaviors have been successfully applied to the characterization of flavone di- C-glycosides found in V. yedoensis. A total of 35 flavonoid glycosides, including 1 flavone mono- C-hexoside, 2 flavone 6,8-di- C-hexosides, 11 flavone 6,8-di- C-pentosides, 13 flavone 6,8- C-hexosyl- C-pentosides, 5 acetylated flavone C-glycosides and 3 flavonol O-glycosides, were identified or tentatively identified on the base of their UV profiles, MS and MSn ( n = 5) data, or by comparing with reference substances. Among these, the acetylated flavone C-glycosides were reported from V. yedoensis for the first time. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Uncertainties in design variables and problem parameters are often inevitable in multi-objective optimizations, and they must be considered in an optimization task if reliable Pareto optimal solutions are to be sought. Multi-objective reliability-based design optimization has been raised as a question in design for reliability, but the disadvantages of fixed evolutionary parameters, nonuniformly distributed Pareto optimal solutions and high computational cost hinder engineering applications of reliability-based design. To deal with it, this work proposes an integrated multi-objective cultural-based particle swarm algorithm to solve the double-loop reliability-based design optimization. In the inner optimization loop, the cultural space is composed of the elitism, situational and normative knowledge to adjust the parameters for swarm space, and the crowding distance ranking is introduced to update the global and local optimum and control the maximum number of solutions in elitism knowledge. The hybrid mean value method is improved to perform reliability analysis in the outer loop to suit both concave and convex types of performance functions. In addition, the car side-impact and the injection molding machine are chosen as multi-objective reliability design examples to demonstrate the effectiveness of the proposed approach. Simultaneously, results of car side-impact problem are compared with two traditional multi-objective reliability optimization algorithms, i.e., nondominated sorting genetic algorithm and crowding distance ranking-based multi-objective particle swarm optimizer, to assess the efficiency of the proposed approach. The results denote the proposed cultural-based multi-objective particle swarm optimizer is effective and feasible to solve the reliability-based design optimization problems. [ABSTRACT FROM AUTHOR]

A combinative method using overpressured layer chromatography ( OPLC) and TLC bioautography against O2•− was developed to separate antioxidants from Glehnia littoralis roots. Through target-directed isolation by the TLC bioautographic method, seven compounds including five antioxidants were rapidly isolated by OPLC and identified as 1-linoloyl-3-palmitoylglycerol, facarindiol, panaxynol, isoimperatorin, β-sitosterol, scopoletin, and umbelliferone from G. littoralis roots. This OPLC method is a very suitable separation technique for light-sensitive polyacetylenes (panaxynol and facarindiol) with higher isolated yields compared to conventional open column chromatography. This is the first report on the separation of polyacetylenes by OPLC. [ABSTRACT FROM AUTHOR]

Cardiac remodelling is a major determinant of heart failure (HF) and is characterised by cardiac hypertrophy, fibrosis, oxidative stress and myocytes apoptosis. Hesperetin, which belongs to the flavonoid subgroup of citrus flavonoids, is the main flavonoid in oranges and possesses multiple pharmacological properties. However, its role in cardiac remodelling remains unknown. We determined the effect of hesperetin on cardiac hypertrophy, fibrosis and heart function using an aortic banding (AB) mouse. Male, 8-10-week-old, wild-type C57 mice with or without oral hesperetin administration were subjected to AB or a sham operation. Our data demonstrated that hesperetin protected against cardiac hypertrophy, fibrosis and dysfunction induced by AB, as assessed by heart weigh/body weight, lung weight/body weight, heart weight/tibia length, echocardiographic and haemodynamic parameters, histological analysis, and gene expression of hypertrophic and fibrotic markers. Also, hesperetin attenuated oxidative stress and myocytes apoptosis induced by AB. The inhibitory effect of hesperetin on cardiac remodelling was mediated by blocking PKCα/βII-AKT, JNK and TGFβ1-Smad signalling pathways. In conclusion, we found that the orange flavonoid hesperetin protected against cardiac remodelling induced by pressure overload via inhibiting cardiac hypertrophy, fibrosis, oxidative stress and myocytes apoptosis. These findings suggest a potential therapeutic drug for cardiac remodelling and HF. [ABSTRACT FROM AUTHOR]

Product platform modular architecture identification is the most critical process to support the incremental design of derivative instances. In order to solve the inflexibility in a single modular or scalable platform of complex mechatronics products, an integrated product modularisation scheme based on flow analysis, design structure matrix (DSM) and fuzzy clustering is proposed to compose a flexible platform. The definition of flexible platform is explained and internal mappings among functions, components and modules are set up. DSM for a kernel product is constructed by the flow analysis between the leaf components in design bill of material. An improved scaling by minimising a convex function algorithm is developed to transform the DSM to vectors in two-dimensional spaces, and the vectors are clustered using the traditional fuzzyc-means algorithm. Cluster centre components are selected to identify modular types with respective functional features. Thus, the internal relationships between components can be modelled with flow analysis-based DSM in a clear format, and the proposed DSM transformation and clustering algorithm identify the modular architecture for a flexible platform in a lower computational complexity. A numerical example and computational comparisons are also given to illustrate the proposed concept and the effectiveness and efficiency of the proposed approach. [ABSTRACT FROM PUBLISHER]

Low-density-lipoprotein (LDL) receptor-related proteins 5 and 6 (LRP5/6) are Wnt co-receptors essential for Wnt/?-catenin signaling. Dickkopf 1 (DKK1) inhibits Wnt signaling by interacting with the extracellular domains of LRP5/6 and is a drug target for multiple diseases. Here we present the crystal structures of a human LRP6-E3E4-DKK1 complex and the first and second halves of human LRP6's four propeller-epidermal growth factor (EGF) pairs (LRP6-E1E2 and LRP6-E3E4). Combined with EM analysis, these data demonstrate that LRP6-E1E2 and LRP6-E3E4 form two rigid structural blocks, with a short intervening hinge that restrains their relative orientation. The C-terminal domain of DKK1 (DKK1c) interacts with the top surface of the LRP6-E3 YWTD propeller and given their structural similarity, probably also that of the LRP6-E1 propeller, through conserved hydrophobic patches buttressed by a network of salt bridges and hydrogen bonds. Our work provides key insights for understanding LRP5/6 structure and the interaction of LRP5/6 with DKK, as well as for drug discovery. [ABSTRACT FROM AUTHOR]

Ski8p is a WD-repeat protein with an essential role for the Ski complex assembly in an exosome-dependent 3′-to-5′ mRNA decay. In addition, Ski8p is involved in meiotic recombination by interacting with Spo11p protein. We have determined the crystal structure of Ski8p from Saccharomyces cerevisiae at 2.2 Å resolution. The structure reveals that Ski8p folds into a seven-bladed β propeller. Mapping sequence conservation and hydrophobicities of amino acids on the molecular surface of Ski8p reveals a prominent site on the top surface of the β propeller, which is most likely involved in mediating interactions of Ski8p with Ski3p and Spo11p. Mutagenesis combined with yeast two-hybrid and GST pull-down assays identified the top surface of the β propeller as being required for Ski8p binding to Ski3p and Spo11p. The functional implications for Ski8p function in both mRNA decay and meiotic recombination are discussed. [ABSTRACT FROM AUTHOR]