Nanjing University

Hongxia Yu

Wei Shi

Qinchang Chen

Yuqian Li

Si Wei

Nanyang Yu

Haoyue Tan

Jing Guo

Xiaoxiang Wang

The present invention provides a model for high-throughput screening of endocrine disruptors and a method for screening the same. In the present invention, primary structural alerts, secondary structural alerts and tertiary structural alerts of compounds are extracted according to a nuclear receptor, and then the primary structural alerts, the secondary structural alerts and the tertiary structural alerts form a nuclear receptor high-throughput screening model; hierarchical structural alert matching is carried out on target compounds through the nuclear receptor high-throughput screening model, and ligand-receptor binding mode analysis and semi-quantitative prediction of binding activity and disrupting activity are performed. According to the present invention, the defect in prior art that potential nuclear receptor-mediated endocrine disruptors cannot be effectively screened in high throughput is overcome, high-throughput screening of potential nuclear receptor-mediated endocrine disruptors can be performed, and receptor competitive activity and A-Anta activity of the nuclear receptor-mediated endocrine disruptors can be determined.

Model for high-throughput screening of endocrine disruptor and method for screening same

Disclosed is a method for high-throughput screening of non-target biomarkers based on metabolic disturbance caused by pollutants, belonging to the field of environmental exposure and health. The method includes the following steps: (1) extracting to obtain extracts to be tested; (2) performing chromatographic analysis to obtain a spectrum containing chromatographic peaks; (3) identifying and labeling features of pollutants, taking chromatographic peaks other than the features of the pollutants as features of potential metabolites, and performing non-target labeling of the features of the potential metabolites; (4) establishing a linear regression model by taking the peak areas of the features of the potential metabolites as dependent variables and the peak areas of the features of the pollutants as independent variables; (5) operating the model, and performing non-target screening of the biomarkers to preliminarily obtain related biomarkers; (6) identifying the MS spectra and MS/MS spectra of the preliminarily obtained biomarkers, and identifying biomarkers related to pollutant exposure. The disclosed method improves the accuracy of biomarker screening and the throughput of biomarker screening.

Method for high-throughput screening of non-target biomarkers based on metabolic perturbation caused by pollutants

Implementations herein relates to effect-directed identification of targeted and non-targeted androgen disruptors. The implementations include primary separation, androgenic activity testing, high throughput separation and preparation of toxicants, active component scanning based on high performance liquid chromatography-time of flight mass spectrometry, targeted screening of suspicious androgenic substances, non-target identification of androgenic compounds combining mass spectrum, chromatography and toxicity characteristics and toxicity confirmation. The implementations perform separation using SPE and preparative separation in series to obtain high throughput separation fractions, utilize DMSO as a protective agent to optimize concentration of second fractions, utilize target databases to achieve target identification of key toxicants. In addition, assess mass spectrum characteristic identification based on TOF-MS library spectrum, assess chromatography characteristic identification methods based on relationship between retention times and characteristics of compounds, assess toxicity characteristic identification methods based on molecular dynamics simulation techniques, and further assess non-targeted identification and determination of key androgenic substances in the fractions.

Effect-directed identification of targeted and non-targeted androgen disruptors

The present patent relates to a method for qualitative identification and quantitative prediction of thyroid hormone disrupting chemicals base on the interaction between thyroid hormone receptor and co-regulators (coactivator and corepressor). The method identifies chemicals as passive antagonists, active antagonists and agonists by means of co-regulator involved molecular dynamics simulations, and predicts the relative disrupting potencies by use of binding free energy, therefore, may be used for screening of thyroid hormone disruptors among environmental pollutants. Upon more comprehensive consideration of the functioning mechanism of thyroid hormone receptor, the present invention is able to sufficiently identify thyroid hormone disruptors as agonists and antagonists, and gives more accurate prediction of the disrupting potency. Further, since nuclear receptors, just as thyroid hormone receptor, are strongly associated with co-regulators, the method may be expanded to the screening of nuclear receptor mediated endocrine disruptors.

Growing community of inventors

Nanjing, China

Hongxia Yu