Pharmacophoric-constrained heterogeneous graph transformer model for molecular property prediction.

Informative representation of molecules is a crucial prerequisite in AI-driven drug design and discovery. Pharmacophore information including functional groups and chemical reactions can indicate molecular properties, which have not been fully exploited by prior atom-based molecular graph representation. To obtain a more informative representation of molecules for better molecule property prediction, we propose the Pharmacophoric-constrained Heterogeneous Graph Transformer (PharmHGT). We design a pharmacophoric-constrained multi-views molecular representation graph, enabling PharmHGT to extract vital chemical information from functional substructures and chemical reactions. With a carefully designed pharmacophoric-constrained multi-view molecular representation graph, PharmHGT can learn more chemical information from molecular functional substructures and chemical reaction information. Extensive downstream experiments prove that PharmHGT achieves remarkably superior performance over the state-of-the-art models the performance of our model is up to 1.55% in ROC-AUC and 0.272 in RMSE higher than the best baseline model) on molecular properties prediction. The ablation study and case study show that our proposed molecular graph representation method and heterogeneous graph transformer model can better capture the pharmacophoric structure and chemical information features. Further visualization studies also indicated a better representation capacity achieved by our model.

Mediation analysis of leisure activities on the association between cognitive function and mortality: a longitudinal study of 42,942 Chinese adults 65 years and older.

OBJECTIVES: Previous studies have established associations of cognitive function and leisure activities with mortality. This study aimed to evaluate whether leisure activities causally mediate these associations. METHODS: This longitudinal study included 42,246 participants aged over 65 years from the Chinese Longitudinal Healthy Longevity Survey. The Mini-Mental State Examination and a self-reported scale were used to measure cognitive status and leisure activities, respectively. We examined the associations of cognitive function and leisure activities with mortality using Cox proportional hazards models. Causal mediation analysis was used to assess whether leisure activities mediated the association between cognitive function and mortality. RESULTS: Cognitive function and leisure activities were inversely associated with mortality. Leisure activities accounted for 28.3% (95% confidence interval [CI], 25.6 to 31.1) of the total effect of cognitive function and mortality. A higher mediated proportion (PM) was observed for physical leisure activities (PM, 20.1%; 95% CI, 18.0 to 22.3) than for social leisure activities (PM, 17.7%; 95% CI, 15.7 to 19.7). The mediating effect was higher among participants at younger ages (PM, 41.5%; 95% CI, 21.3 to 65.4), those with higher education levels (PM, 30.5%; 95% CI, 25.3 to 36.2), and residents of rural China (PM, 42.5%; 95% CI, 25.4 to 62.5). CONCLUSIONS: Cognitive function was associated with inverse mortality. Leisure activities significantly mediated this association. Participation in leisure activities at the early stages of mild cognitive impairment could reduce the risk of mortality, which has a major impact on interventional strategies for healthy aging.

[Rapid determination of thiabendazole and carbendazim in concentrated fruit juices by ultra-high performance liquid chromatography-tandem mass spectrometry].

A method was developed for the rapid determination of thiabendazole and carbendazim residues in concentrated fruit juices by using ultra-high performance liquid chromatography (UHPLC) coupled with triple quadrupole tandem mass spectrometry (MS/MS), and quantified by matrix-matched standard solution in external standard method. The residues in the samples were extracted by ethyl acetate, and then analyzed by using UHPLC-MS/MS in multiple reaction monitoring (MRM) mode via positive electrospray ionization with an Waters ACQUITY UPLC BEH C18 column (50 mm x 2.1 mm, 1.7 µm) as the analytical column. Good linearities were obtained in the range of 0.5-10 µg/kg for both pesticides with correlation coefficients greater than 0. 99. The recovery experiments were carried out by spiking standards into blank samples of apple, peach, orange, pear, grape juices at three levels of 0.5, 1.0 and 5.0 µg/kg. The recoveries of thiabendazole and carbendazim were from 76.98% to 108.7% with the relative standard deviations (RSD) of 2.95%-9.99%. For both pesticides in different matrices, the limits of detection (S/N = 3) were in the range of 0.12-0.23 µg/kg. Meanwhile, the pyrolysis mechanism and matrix effects for the determination of thiabendazole and carbendazim in concentrated fruit juices were investigated in this study. The method is simple, rapid and accurate, and can be used for the routine analysis of thiabendazole and carbendazim in concentrated fruit juices.

[Determination of trace musk xylene and musk ketone in aquatic products by multiple adsorption synchronous purification-gas chromatography-mass spectrometry].

In order to investigate the residues of musk xylene and musk ketone in aquatic products, a method was established for the determination of the trace musk xylene and musk ketone in aquatic products by multiple adsorption synchronous purification (MASP) -gas chromatography-mass spectrometry (GC-MS). After extracted with acetonitrile, the samples were pretreated using MASP method including extraction, salting-out and purification processes, analyzed with GC-MS in the selected ion monitoring (SIM) mode, and then quantified by matrix-matched standard solution in external standard method. The analysis was carried out with a capillary column (DB-5 MS, 30 m x 0.25 mm x 0.25 microm) under electron ionization conditions. The quantification was performed using monitoring ions of m/z 282, 297, 265 for musk xylene and m/z 279, 294, 191 for musk ketone. The results showed good linearity in the range of 1-100 microg/kg for musk xylene and musk ketone with the correlation coefficients not less than 0.999, and the limits of detection (S/N = 3) of 0.30 microg/kg. The average recoveries of musk xylene and musk ketone spiked in prawn, clam and sea eel blank samples at three spiked levels of 1.0, 2.0 and 10.0 microg/kg ranged from 79% to 104% and the RSDs were in the range of 1.6%-13.3%. The method is simple, rapid and accurate, and can be used for the routine analysis of musk xylene and musk ketone in aquatic products.