Synthetic Peroxides Promote Apoptosis of Cancer Cells by Inhibiting P-Glycoprotein ABCB5

This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC₅₀=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma.     

Sustainable ammonia production through process synthesis and global optimization

Current ammonia production technologies have a significant carbon footprint. In this study, we present a process synthesis and global optimization framework to discover the efficient utilization of renewable resources in ammonia production. Competing technologies are incorporated in a process superstructure where biomass, wind, and solar routes are compared with the natural gas-based reference case. A deterministic global optimization-based branch-and-bound algorithm is used to solve the resulting large-scale nonconvex mixed-integer nonlinear programming problem (MINLP). Case studies for Texas, California, and Iowa are conducted to examine the effects of different feedstock prices and availabilities. Results indicate that profitability of ammonia production is highly sensitive to feedstock and electricity prices, as well as greenhouse gas (GHG) restrictions. Under strict 75% GHG reductions, biomass to ammonia route is found to be competitive with natural gas route, whereas wind and solar to ammonia routes require further improvement to compete with those two routes. © 2018 American Institute of Chemical Engineers AIChE J, 65: e16498 2019     

Quality assurance of Chinese herbal medicines: Procedure for multiple‐herb extraction

A quality assurance (QA) procedure for multiple‐herb extraction, which takes into account the existence of common chemical markers and multiple‐herb‐extraction effects, has been developed for producing Chinese herbal medicines (CHMs) of consistent quality. The experimental method for determining related correlation function of the multiple‐herb‐extraction effect was designed. A systematic solution strategy was also developed to appropriately decompose the multiple‐herb extraction system into several subsystems for obtaining solution(s) and determining the overall behavior of the system. An example of QA of Danshen–Gegen (DG) decoction was used to demonstrate the QA procedure. An H9c2 cell assay was used to test the efficacy of consistent quality DG decoctions prepared by different herb combinations with different material costs of herbs. It was observed that a multiple‐herb‐extraction effect was present in the aqueous extraction of Danshensu and this effect was depended on the extraction solvent. The possible mechanism of this multiple‐herb‐extraction effect in the aqueous DG extraction was speculated to be the change of initial pH value of the aqueous extraction solvent by an unknown component from Gegen. The experimental chemical marker concentrations fell within ±10% of the specified chemical marker compositions by using the amount of herb from each herb class as predicted by the QA model. Furthermore, an H9c2 cell assay was used to test the efficacy of three consistent quality DG extracts, which were produced by different herb combinations with different material costs of herbs. The results showed that the three DG extracts provided consistent biological efficacy against menadione‐induced toxicity. This study extended a recently developed QA procedure of single‐herb extraction to multiple‐herb extraction. It provides a solution of QA in extraction, which is one of the most important unresolved problems in the modernization of traditional Chinese medicines. With this modified model and the companion experiments, the amount of herbs needed from different quality classes to produce a multiple‐herb formula CHM product decoction with consistent quality can be exactly determined. © 2014 American Institute of Chemical Engineers AIChE J 60: 4014–4026, 2014     

Sustainable Urban Development Issues in Chinese Transitional Cities: Hong Kong and Shenzhen

Post-colonial capitalist Hong Kong and rapidly developing Shenzhen in China's socialist market economy have both adopted a pro-growth strategy to cope with challenges imposed by a globalizing economy. This development philosophy has exerted tremendous pressure on both cities, pushing them further away from the path of sustainable urban development. Despite the policy rhetoric of pursuing sustainable development, both city governments have refrained from identifying and analysing sustainable urban development issues. While the top-down elite-dominated polities in Hong Kong and Shenzhen are working hard to attain world city status, both cities lack a sustainable development strategy. Without a critical rethink of the growth-first mentality, sustainability principles such as an ethical utilization of natural resources and aspirations for intra- and inter-generational equity are not put on the policy agenda. Despite recent efforts to clean up the environment, it is uncertain how these two growing cities will proceed as the global economy itself is starting to capitalize on sustainability efforts to further capital accumulation.     

ABCG5/G8 Deficiency in Mice Reduces Dietary Triacylglycerol and Cholesterol Transport into the Lymph

The adenosine triphosphate‐binding cassette (ABC) transporter G5/G8 is critical in protecting the body from accumulating dietary plant sterols. Expressed in the liver and small intestine, it transports plant sterols into the biliary and intestinal lumens, thus promoting their excretion. The extent to which G5/G8 regulates cholesterol absorption remains unclear. G5/G8 is also implicated in reducing the absorption of dietary triacylglycerols (TAG) by unknown mechanisms. We hypothesized that G5/G8 suppresses the production of chylomicrons, and its deficiency would enhance the absorption of both dietary TAG and cholesterol. The aim of this study was to investigate the effects of G5/G8 deficiency on lipid uptake and secretion into the lymph under steady‐state conditions. Surprisingly, compared with wild‐type mice (WT) (n = 9), G5/G8 KO (n = 13) lymph fistula mice given a continuous intraduodenal infusion of [3H]‐TAG and [14C]‐cholesterol showed a significant (P < 0.05) reduction in lymphatic transport of both [³H]‐TAG and [¹⁴C]‐cholesterol, concomitant with a significant (P < 0.05) increase of [³H]‐TAG and [¹⁴C]‐cholesterol accumulated in the intestinal lumen. There was no difference in the total amount of radiolabeled lipids retained in the intestinal mucosa between the two groups. G5/G8 KO mice given a bolus of TAG showed reduced intestinal TAG secretion compared with WT, suggesting an independent role for G5/G8 in facilitating intestinal TAG transport. Our data demonstrate that G5/G8 deficiency reduces the uptake and secretion of both dietary TAG and cholesterol by the intestine, suggesting a novel role for the sterol transporter in the formation and secretion of chylomicrons.     

Process parameters selection for laser polishing DF2 (AISI O1) by Nd:YAG pulsed laser using orthogonal design

Mechanisms of laser polishing metals in a continuous scanning mode, as envisaged and analyzed in this paper, are rather complex, and experimental optimization of laser polishing metallic material is very time-consuming and difficult. Aiming at shortening the experimental time in achieving a better surface finishing of DF2 (AISI 01) tool steel by pulse Nd:YAG laser, we used the orthogonal experimental design for selecting the laser operational parameters. The results showed that the orthogonal design (OD) allowed the optimum technological parameters for the laser polishing to be obtained quickly and effectively. According to the OD analysis and experimental data, the attainable optimum laser smoothening/polishing parameters from this study are pulse energy (P)?=?1?J, feed rate?=?300–400?mm/min, pulse duration?=?3?ms, and pulse frequency (f)?=?20–25?Hz. The work in this paper demonstrates the relative superiority of orthogonal design in saving experimental times and providing good laser polishing surface in surface texturing and the smoothening process.