Simultaneous determination of three 5-nitroimidazoles in foodstuffs by differential pulse voltammetry and chemometrics

The voltammetric behaviour of three 5-nitroimidazoles,metronidazole,tinidazole and ornidazole,was investigated,and a method was developed for the simultaneous determination of these compounds,based on their reduction at a hanging mercury drop electrode（HMDE） in pH 8.95 buffer with differential pulse voltammetric（DPV） approach.Well defined voltammetric waves with peak potentials of -692,-640 and -652 mV were observed for these compounds,respectively.It is difficult to determine them individually from their mixtures without preseparation,for their voltammetric peaks overlapped seriously,so the chemometrics were used to resolve the overlapped voltammogram and quantify the mixtures.The proposed method was successfully applied to the determination of three 5-nitroimidazoles in milk and honey samples.

Prediction of Enhancement Effect of Nitroimidazoles on Irradiation by Gene Expression Programming

A novel machine learning method, gene expression programming（GEP）, was employed to build quatitative structure-activity relationship（QSAR） models for predicting the enhancement effect of nitroimidazole compounds on irradiation. The models were based on descriptors which were calculated from the molecular structures. Four descriptors were selected from the pool of descriptors by best multiple linear regression（BMLR） method. After that, three regression methods, multiple linear regression（MLR）, support vector machine（SVM） and GEP, were used to build QSAR models. Compared to MLR and SVM, GEP produced a better model with the square of correlation coefficient（R2）, 0.9203 and 0.9014, and the root mean square error（RMSE）, 0.6187 and 0.6875, for training set and test set, respectively. The results show that the GEP model has better predictive ability and more reliable than the MLR and SVM models. This indicates that GEP is a promising method on relevant researches in radiation area.

A neutrophil-biomimic platform for eradicating metastatic breast cancer stem-like cells by redox microenvironment modulation and hypoxia-triggered differentiation therapy

Metastasis accounts for 90%of breast cancer deaths,where the lethality could be attributed to the poor drug accumulation at the metastatic loci.The tolerance to chemotherapy induced by breast cancer stem cells(BCSCs)and their particular redox microenvironment further aggravate the therapeutic dilemma.To be specific,therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly,and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy.Herein,we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability,and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole(NI)to yield two hypoxia-responsive prodrugs,which could be encapsulated into a polymeric nitroimidazole core.The platform can actively target the lung metastasis sites of triple negative breast cancer(TNBC),and release the escorted drugs upon being triggered by the hypoxia microenvironment.During the responsiveness,the differentiating agent could promote transferring BCSCs into non-BCSCs,and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen(NADPH)and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs.In combination,the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity,and remarkably suppress tumor growth and lung metastasis.Hopefully,this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.