Abstract In order to reveal the inhibitory effect of pomegranate punicalagin on macrophage foam cell formation and its possible mechanism, Raw264.7 macrophages were as the experimental carrier to detect the effect of punicalagin on macrophage cholesterol accumulation and outflow, and evaluate the regulation of punicalagin on cholesterol accumulation related genes CD36, PPARγ and outflow related genes ABCA1/G1, LXRα by Western-Blot method. The results showed that punicalagin can inhibit the cholesterol accumulation in raw264.7 macrophages due to restraining the PPARγ-CD36 expression, and meanwhile it could also promote macrophage cholesterol efflux by regulating LXRα-ABCA1/G1 pathway. mechanism Raw2647 Raw Raw264 7 Raw264. CD36 CD ABCA1G1 ABCAG ABCA1 G1 ABCA G ABCA1/G1 WesternBlot Western Blot method raw2647 raw raw264 raw264. PPARγCD36 PPARγCD PPARγ-CD3 expression LXRαABCA1/G1 LXRαABCA1G1 LXRαABCAG LXRα-ABCA1/G pathway Raw26 CD3 ABCA1G ABCA1/G raw26 PPARγCD3 PPARγ-CD LXRαABCA1 LXRαABCA LXRαABCA1/G LXRαABCA1G Raw2 raw2

A rapid and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine sacubitril, valsartan and a metabolite of sacubitril (LBQ657) in human plasma using sacubitril-d4 and valsartan-d3 as the internal standards. Following protein precipitation, the analytes were operated on an Ultimate® XB-C18 column (2.1 × 50 mm, 3.5 μm, Welch) with a gradient elution with acetonitrile, and 5 mM ammonium acetate and 0.1% formic acid in water as the mobile phase. The detection was performed on a Triple Quad™ 4000 mass spectrometer coupled with an electrospray ionization source (ESI) under positive-ion multiple reaction monitoring mode. The linearities are 2.00-4000, 5.00-10000 and 5.00-10000 ng mL−1 for sacubitril, valsartan and LBQ657, respectively. The accuracy and precision of intra- and inter-day, dilution accuracy, recovery and stability of the method were all within the acceptable limits and no matrix effect or carryover was observed. The suitability of the method was successfully demonstrated in terms of the quantification of sacubitril, valsartan and LBQ657 in plasma samples collected from healthy Chinese volunteers in a clinical trial.

Abstract: Contrary to the traditional economic prediction that prices decrease as more firms enter the market, this paper finds a non-monotonic relationship between the number of firms and prices in online book markets. A substantial decrease in posted prices is observed when the market moves from a monopoly to duopoly. Surprisingly, as the market further expands, posted prices converge to monopoly price rather than competitive price. This is because as the number of sellers increase on the internet, the cost for consumers to obtain accurate information as well as the cost to evaluate products and sellers increase. Thus, the existence of a large number of sellers deter consumer search and lead to more random purchases. With little consumer search, sellers’ returns to undercutting price reduce. Therefore, instead of lowering price when faced with more competitors, sellers increase prices.