NeuTox: A weighted ensemble model for screening potential neuronal cytotoxicity of chemicals based on various types of molecular representations.

Chemical-induced neurotoxicity has been widely brought into focus in the risk assessment of chemical safety. However, the traditional in vivo animal models to evaluate neurotoxicity are time-consuming and expensive, which cannot completely represent the pathophysiology of neurotoxicity in humans. Cytotoxicity to human neuroblastoma cell line (SH-SY5Y) is commonly used as an alternative to animal testing for the assessment of neurotoxicity, yet it is still not appropriate for high throughput screening of potential neuronal cytotoxicity of chemicals. In this study, we constructed an ensemble prediction model, termed NeuTox, by combining multiple machine learning algorithms with molecular representations based on the weighted score of Particle Swarm Optimization. For the test set, NeuTox shows excellent performance with an accuracy of 0.9064, which are superior to the top-performing individual models. The subsequent experimental verifications reveal that 5,5'-isopropylidenedi-2-biphenylol and 4,4'-cyclo-hexylidenebisphenol exhibited stronger SH-SY5Y-based cytotoxicity compared to bisphenol A, suggesting that NeuTox has good generalization ability in the first-tier assessment of neuronal cytotoxicity of BPA analogs. For ease of use, NeuTox is presented as an online web server that can be freely accessed via http://www.iehneutox-predictor.cn/NeuToxPredict/Predict.

Screening of the Antagonistic Activity of Potential Bisphenol A Alternatives toward the Androgen Receptor Using Machine Learning and Molecular Dynamics Simulation.

Over the past few decades, extensive research has indicated that exposure to bisphenol A (BPA) increases the health risks in humans. Toxicological studies have demonstrated that BPA can bind to the androgen receptor (AR), resulting in endocrine-disrupting effects. In recent investigations, many alternatives to BPA have been detected in various environmental media as major pollutants. However, related experimental evaluations of BPA alternatives have not been systematically implemented for the assessment of chemical safety and the effects of structural characteristics on the antagonistic activity of the AR. To promote the green development of BPA alternatives, high-throughput toxicological screening is fundamental for prioritizing chemical tests. Therefore, we proposed a hybrid deep learning architecture that combines molecular descriptors and molecular graphs to predict AR antagonistic activity. Compared to previous models, this hybrid architecture can extract substantial chemical information from various molecular representations to improve the model's generalization ability for BPA alternatives. Our predictions suggest that lignin-derivable bisguaiacols, as alternatives to BPA, are likely to be nonantagonist for AR compared to bisphenol analogues. Additionally, molecular dynamics (MD) simulations identified the dihydrotestosterone-bound pocket, rather than the surface, as the major binding site of bisphenol analogues. The conformational changes of key helix H12 from an agonistic to an antagonistic conformation can be evaluated qualitatively by accelerated MD simulations to explain the underlying mechanism. Overall, our computational study is helpful for toxicological screening of BPA alternatives and the design of environmentally friendly BPA alternatives.

Investigation of the Binding Fraction of PFAS in Human Plasma and Underlying Mechanisms Based on Machine Learning and Molecular Dynamics Simulation.

More than 7000 per- and polyfluorinated alkyl substances (PFAS) have been documented in the U.S. Environmental Protection Agency's CompTox Chemicals database. These PFAS can be used in a broad range of industrial and consumer applications but may pose potential environmental issues and health risks. However, little is known about emerging PFAS bioaccumulation to assess their chemical safety. This study focuses specifically on the large and high-quality data set of fluorochemicals from the related environmental and pharmaceutical chemicals databases, and machine learning (ML) models were developed for the classification prediction of the unbound fraction of compounds in plasma. A comprehensive evaluation of the ML models shows that the best blending model yields an accuracy of 0.901 for the test set. The predictions suggest that most PFAS (∼92%) have a high binding fraction in plasma. Introduction of alkaline amino groups is likely to reduce the binding affinities of PFAS with plasma proteins. Molecular dynamics simulations indicate a clear distinction between the high and low binding fractions of PFAS. These computational workflows can be used to predict the bioaccumulation of emerging PFAS and are also helpful for the molecular design of PFAS to prevent the release of high-bioaccumulation compounds into the environment.

Research progress on the psychological impacts of passive social media using among adolescents / 中国学校卫生

Abstract@#This paper summarizes the psychological impacts of passive social media use on adolescents by systematically reviewing the existing domestic and foreign literature about passive social media use. The results showed that the psychological impacts of passive social media use included cognitive outcomes (self concept clarity, self esteem), affective outcomes (depression, anxiety, envy, loneliness), subjective well being (life satisfaction), more types of social media (social short form video), detailed information on forms of passive use, as well as possible impacts (positive psychological, social, and behavioral outcomes) on teenagers and college students should be exlpored by utilizing multiple methods(longitudinal study, the grounded theory) are expected in future studies.