An Immune-Inspired Approach with Interval Allocation in Solving Multimodal Multi-Objective Optimization Problems with Local Pareto Sets

In practical engineering,multi-objective optimization often encounters situations where multiple Pareto sets(PS)in the decision space correspond to the same Pareto front(PF)in the objective space,known as Multi-Modal Multi-Objective Optimization Problems(MMOP).Locating multiple equivalent global PSs poses a significant challenge in real-world applications,especially considering the existence of local PSs.Effectively identifying and locating both global and local PSs is a major challenge.To tackle this issue,we introduce an immune-inspired reproduction strategy designed to produce more offspring in less crowded,promising regions and regulate the number of offspring in areas that have been thoroughly explored.This approach achieves a balanced trade-off between exploration and exploitation.Furthermore,we present an interval allocation strategy that adaptively assigns fitness levels to each antibody.This strategy ensures a broader survival margin for solutions in their initial stages and progressively amplifies the differences in individual fitness values as the population matures,thus fostering better population convergence.Additionally,we incorporate a multi-population mechanism that precisely manages each subpopulation through the interval allocation strategy,ensuring the preservation of both global and local PSs.Experimental results on 21 test problems,encompassing both global and local PSs,are compared with eight state-of-the-art multimodal multi-objective optimization algorithms.The results demonstrate the effectiveness of our proposed algorithm in simultaneously identifying global Pareto sets and locally high-quality PSs.

Research and Discussion on Flipped Classroom Combined with Case-Based Learning in Pharmacoeconomics Teaching

Objective:To explore the application effect of flipped classroom combined with case-based learning teaching methods in pharmacoeconomics teaching.Methods:The students majoring in clinical pharmacy in 2019 were selected as the study subjects,and the cost-effectiveness analysis of different dosage forms of Yinzhihuang in the treatment of neonatal jaundice was selected as the teaching case.The flipped classroom combined with case-based learning teaching method was used to carry out theoretical teaching to the students.After the course,questionnaires were distributed through the Sojump platform to evaluate the teaching effect.Results:The results of the questionnaire showed that 85.71%of the students believed that the flipped classroom combined with case-based learning teaching method was helpful in mobilizing the learning enthusiasm and initiative,and improving the comprehensive application ability of the knowledge of pharmacoeconomics.92.86%of the students think that it is conducive to the understanding and memorization of learning content,as well as the cultivation of teamwork,communication,etc.Conclusion:Flipped classroom combined with case-based learning teaching method can improve students’knowledge mastery,thinking skills,and practical application skills,as well as optimize and improve teachers’teaching levels.

Capacity Optimization Configuration of Hydrogen Production System for Offshore Surplus Wind Power

To solve the problem of residual wind power in offshore wind farms,a hydrogen production system with a reasonable capacity was configured to enhance the local load of wind farms and promote the local consumption of residual wind power.By studying the mathematical model of wind power output and calculating surplus wind power,as well as considering the hydrogen production/storage characteristics of the electrolyzer and hydrogen storage tank,an innovative capacity optimization allocation model was established.The objective of the model was to achieve the lowest total net present value over the entire life cycle.The model took into account the cost-benefit breakdown of equipment end-of-life cost,replacement cost,residual value gain,wind abandonment penalty,hydrogen transportation,and environmental value.The MATLAB-based platform invoked the CPLEX commercial solver to solve the model.Combined with the analysis of the annual average wind speed data from an offshore wind farm in Guangdong Province,the optimal capacity configuration results and the actual operation of the hydrogen production system were obtained.Under the calculation scenario,this hydrogen production system could consume 3,800 MWh of residual electricity from offshore wind power each year.It could achieve complete consumption of residual electricity from wind power without incurring the penalty cost of wind power.Additionally,it could produce 66,500 kg of green hydrogen from wind power,resulting in hydrogen sales revenue of 3.63 million RMB.It would also reduce pollutant emissions from coal-based hydrogen production by 1.5 tons and realize an environmental value of 4.83 million RMB.The annual net operating income exceeded 6 million RMB and the whole life cycle NPV income exceeded 50 million RMB.These results verified the feasibility and rationality of the established capacity optimization allocation model.The model could help advance power system planning and operation research and assist offshore wind farm operators in improving economic and environmental benefits.

基于三重四级杆质谱仪的一种定向细胞结合的植物化学组分筛选策略:发现中药制剂消癌平注射液中的潜在生物活性成分

消癌平注射液(XAP-Ⅰ)提取自通关藤,在我国临床上广泛用于治疗各种癌症,而从其复杂组分中阐释生物活性成分一直是学界研究的热点内容。本文结合三重四级杆质谱仪中的全扫描(full scan,FS)、母离子扫描(precursor ion scan,PCIS)、子离子扫描(product ion,PDIS)及多反应监测(multiple reaction monitoring,MRM)模式鉴定了XAP-Ⅰ中的主要孕甾烷糖苷及酚酸类成分,可利用丰富的加合离子信息确定组分结构特性并实现高灵敏度分析。此外,本文应用定向细胞结合植物化学组分筛选策略以发现XAP-Ⅰ中的生物活性成分,该策略可实现对XAP-Ⅰ的高通量定性、定量分析,并显著提高XAP-Ⅰ潜在生物活性成分筛选的灵敏度及选择性。

Potential mechanism of cholagogic effect about Gardenia Jasminoides Ellis(Zhizi)-mediated increase of bile acids urinary excretion in normal rats

Objectives： Gardenia Jasminoides Ellis（Zhizi）, belonging to Rubiaceae family, has been traditionally used for treatment cholestasis and jaundice for centuries in Asian countries. In the theory of Traditional Chinese Medicines, Zhizi could dispel dampness and heat via the urine to execute its choleretic effects. However, the potential molecular mechanism has been still poorly clarified. Here, we investigated the effect of different dose of Zhizi aqueous extract powder（0.3 g/kg/d and 0.9 g/kg/d） on urinary excretion of bile acids（BAs）, and defined the potential mechanism via renal BAs efflux transporters Mrp2 and Mrp4 in normal rats.Methods： Male Wistar rats were orally administrated with 0.3 or 0.9 g/kg/d dose of Zhizi aqueous extract powder for 2 weeks, then body weight, serum aminotransferase, total BAs concentrations in liver, bile,serum, kidney and urine, 1 h bile flow, 12-h urinary volume, biliary and urinary excretion amount of total BAs as well as protein expression of major renal BAs efflux transporter Mrp2 and Mrp4, were all evaluated.Results： Zhizi especially the high dose of Zhizi aqueous extract powder could reduce hepatic total BAs concentration. Additionally, bile flow and biliary excretion had no significant difference, but the remarkable increasing urinary excretion of BAs and 2 to 3 folds up-regulated renal Mrp2 expression were observed after administrated with Zhizi as compared with the control group.Conclusion： The findings indicate that Zhizi reduces hepatic total BAs level by increasing urinary excretion rather than the biliary excretion of BAs, which, in turn ascribed to elevated protein expression of Mrp2 at apical membrane of renal tubular epithelial cells.

Acetaminophen-induced hepatotoxicity in rats is correlated with the accumulation of bile acids: an underlying mechanism

In the present study, we aimed to investigate the underlying mechanism of acetaminophen（APAP）-induced hepatotoxicity by measuring the expression levels of liver transporters and concentrations of bile acids（BAs） in rat plasma and liver. SD rats（42） were randomly assigned into six groups, including 6-h control group, APAP 6-h group, 12-h control group, APAP 12-h group, 24-h control group and APAP 24-h group. The estimation study of BAs in plasma and liver was performed on LC-MS/MS. The levels of bile salt export pump（Bsep）, multidrug resistant protein 2（Mrp2）, multidrug resistant protein 4（Mrp4）, Na＋/taurocholate cotransporting polypeptide（Ntcp） and organic anion transporting polypeptide 2（Oatp2） in the liver were analyzed by Western blotting analysis. Compared with the corresponding control groups, no difference was found in the BA levels and the expressions of BA transporters in the plasma and liver after 6 h of APAP administration. While BA levels were significantly decreased in the plasma and increased in the liver after 12 h of APAP administration（P0.05）; and the expressions of Bsep and Mrp2 were significantly reduced（P0.05）. After 24 h of APAP administration, BA levels were both greatly increased in the plasma and liver（P0.05）; and the expressions of Mrp4 and Oatp2 were significantly decreased（P0.05）. In response to over-dose APAP, Bsep, Mrp2, Mrp4 and Oatp2 levels were reduced at different time points, causing the accumulation of BAs, and such accumulation may ultimately lead to the severe liver injury, which could be an underlying mechanism of the APAP-induced hepatotoxicity.