Emodin is the main component of traditional Chinese medicines including rhubarb, Polygonum multiflorum, and Polygonum cuspidatum. It has confirmed hepatotoxicity and may be the main causative agent of liver damage associated with the above-mentioned traditional Chinese medicines. However, current research does not explain the mechanism of emodin in hepatotoxicity. In this study, L02 cells were used as a model to study the mechanism of emodin-induced hepatocyte apoptosis using quantitative proteomics, and the results were verified by Western blot. A total of 662 differentially expressed proteins were discovered and analyzed using Gene Ontology (GO) and pathway enrichment analysis. The results show that the oxidative phosphorylation pathway is highly represented. Abnormalities in this pathway result in impaired mitochondrial function and represent mitochondrial damage. This result is consistent with mitochondria membrane potential measurements. Analysis of differentially expressed proteins revealed that emodin mainly affects oxidative phosphorylation pathways by inhibiting the function of the mitochondrial respiratory chain complexes; the mitochondrial respiratory chain complex activity assay result also confirmed that emodin could inhibit the activity of all mitochondrial complexes. This results in an increase in caspase-3, a decrease in mitochondrial membrane potential (MMP,) an increase in reactive oxygen species (ROS), and disorders in ATP synthesis, etc., eventually leading to mitochondrial damage and hepatocyte apoptosis in vitro.

Pluronic F127 (F127), an amphiphilic triblock copolymer, has been shown to have significant potential for drug delivery, as it is able to incorporate hydrophobic drugs and self-assemble into nanosize micelles. However, it suffers from dissociation upon dilution owing to the relatively high critical micelle concentration and lack of stimuli-responsive behavior. Here, we synthesized the α-tocopherol (TOC) modified F127 polymer (F127-SS-TOC) via a redox-sensitive disulfide bond between F127 and TOC, which formed stable micelles at relatively low critical micelle concentration and was sensitive to the intracellular redox environment. The particle size and zeta potential of the F127-SS-TOC micelles were 51.87±6.39 nm and -8.43±2.27 mV, respectively, and little changes in both particle size and zeta potential were observed within 7 days at room temperature. With 10 mM dithiothreitol stimulation, the F127-SS-TOC micelles rapidly dissociated followed by a significant change in size, which demonstrated a high reduction sensitivity of the micelles. In addition, the micelles showed a high hemocompatibility even at a high micelle concentration (1,000 μg/mL). Low cytotoxicity of the F127-SS-TOC micelles at concentrations ranging from 12.5 μg/mL to 200 μg/mL was also found on both Bel 7402 and L02 cells. Overall, our results demonstrated F127-SS-TOC micelles as a stable and safe aqueous formulation with a considerable potential for drug delivery.

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Background In today's society, with the sustainable development of economy, material products are rich and diverse. The production speed of products has far exceeded people's needs. Emission reduction and environmental protection have become people's new pursuit. Closed loop supply chain should consider not only product life cycle and recycling, but also economic and environmental benefits. It has become the focus of scholars all over the world. Closed loop supply chain refers to the complete supply chain cycle from procurement to final sales, including product recovery and reverse logistics supported by life cycle. It is a highly complex process. In the closed-loop supply chain, the simplest form is composed of manufacturers, retailers and recyclers. Recycler is the most critical link in the new closed-loop supply chain system, which is not available in the traditional supply chain. Therefore, this paper mainly studies the change of recyclers when exogenous variables fluctuate from the perspective of economic psychology. Research Objects and Methods Most scholars use short-term static methods when studying the uncertainty of recyclers in closed-loop supply chain. It is particularly important to analyze the uncertain factors in the closed-loop supply chain. In order to analyze this problem, this paper first improves the closed-loop supply chain model of capital flow and logistics coupling, so as to better simulate the real closed-loop supply chain. Secondly, the sensitivity analysis function of Vensim software is used to simulate the impact of exogenous variables on the inventory value and capital value of recyclers in the closed-loop supply chain model. At the same time, in order to verify the impact of recyclers' emotional stability, this study adopts the following scale. The communication anxiety scale adopts 15 questions of the Interaction Anxiety Scale (IAS) compiled by Leary, with a single dimension and a 5-level score, from 1 to 5 to “very inconsistent”. The higher the score, the greater the degree of social anxiety. The emotion regulation self-efficacy scale adopts the emotion regulation self-efficacy scale (RES) revised by Caprara. The 12 questions are divided into three dimensions: expressing positive emotions, managing depression / pain and self-efficacy of managing anger / anger, with 4 questions in each dimension. A 5-level score is adopted, from 1 to 5, which means “very inconsistent” to “very consistent”. The higher the score, the higher the degree of self-confidence in regulating their emotions. In the study, Cronbach's α The coefficient is 0.80. The aggression scale adopts the aggression scale (bpaq) compiled by Buss and Perry The scale has 29 questions and is divided into four dimensions: physical aggression, verbal aggression, anger and hostility. The higher the score, the stronger the attack. In this study, Cronbach's α The coefficient is 0.85. The depression questionnaire adopts Beck's revised depression Inventory-II (BDI-II). The questionnaire has 21 questions, with a single dimension. The higher the total score, the heavier the degree of depression. The data were obtained by spss19 0 and amos17 0 for analysis. Results the 19 exogenous variables were divided into four categories: Manufacturer related parameters, retailer related parameters, recycler related parameters and other related parameters. The sensitivity of these 19 parameters to recycler inventory and capital in closed-loop supply chain is simulated and analyzed. Through the comparative analysis of sensitivity chart, it can be seen that the manufacturer's inventory adjustment time, the retailer's safety inventory coefficient, the retailer's smoothing time, the retailer's inventory adjustment time, the collector's fixed expenditure and the collector's initial inventory value are positively correlated. And have a significant impact on collectors' inventory and emotional stability. The reason is that appropriate time adjustment helps to reduce work pressure and naturally improve job satisfaction. Conclusion in the closed-loop supply chain, the fluctuation of the same exogenous variable in the same range has a more significant impact on the recycler's inventory than on the recycler's capital. For recyclers, the decline of inventory value has a positive impact on the capital of recyclers, while the decline of capital value has a negative impact on the capital of recyclers. The impact of retailer order smoothing time on recycler inventory and capital is uncertain. Therefore, recyclers should strengthen fund management, establish insurance mechanism and prepare reserves to prevent the impact of external variable fluctuations on recyclers' funds. At the same time, in view of the uncertainty caused by exogenous variables related to manufacturers and retailers on recyclers' funds and inventory, recyclers need to deal with it through information sharing, compensation mechanism, incentive and other ways. Acknowledgements Supported by a project grant from National Natural Science Foundation of China (Grant No.71764019), the National Social Science Foundation of China (Grant No.19BGL187), the Planning Project of Philosophy and Social Science of Inner Mongolia (Grant No.2021NDB082), Inner Mongolia Natural Science Foundation (Grant No.2021MS07016 and 2020MS07020) and Research Center for Resources, Environment and Energy Development Strategic.