Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model.

Recent trends suggest that Chinese herbal medicine formulas (CHM formulas) are promising treatments for complex diseases. To characterize the precise syndromes, precise diseases and precise targets of the precise targets between complex diseases and CHM formulas, we developed an artificial intelligence-based quantitative predictive algorithm (DeepTCM). DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling, molecular and theoretical levels of traditional Chinese medicine (TCM). As an example, our model simulated the optimal CHM formulas for the treatment of coronary heart disease (CHD) with depression, and through model sensitivity analysis, we calculated the balanced scoring of the formulas. Furthermore, we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions. Finally, we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice. This novel multiscale model opened up a new avenue to combine "disease syndrome" and "macro micro" system modeling to facilitate translational research in CHM formulas.

The II-I Phase Transition Behavior of Butene-1 Copolymers with Hydroxyl Groups.

The crystallization and II-I phase transition of functionalized polybutene-1 with hydroxyl groups were investigated by differential scanning calorimetry. The results show that the incorporated hydroxyl groups increase the nucleation density but decrease the growth rate in melt crystallization. Interestingly, for the generated tetragonal form II, the presence of polar hydroxyl groups can effectively accelerate the phase transition into the thermodynamically stable modification of trigonal form I, especially with stepwise annealing and high incorporation. Using stepwise annealing, II-I phase transition was enhanced by an additional nucleation step performed at a relatively low temperature, and the optimal nucleation temperature to obtain the maximum transition degree was ‒10 °C, which is independent from the content of hydroxyl groups. Furthermore, the accelerating effect of hydroxyl groups on the II-I transition kinetics can be increased by reducing the crystallization temperature when preparing form II crystallites. These results provide a potential molecular design approach for developing polybutene-1 materials.

Thermal Analysis of Crystallization and Phase Transition in Novel Polyethylene Glycol Grafted Butene-1 Copolymers.

Copolymerization is an effective strategy to regulate the molecular structure and tune crystalline structures. In this work, novel butene-1 copolymers with different polyethylene glycol (PEG) grafts (number-average molecular weight Mn = 750, 2000, and 4000 g/mol) were synthesized, for the first time introducing long-chain grafts to the polybutene-1 main chain. For these PEG-grafted copolymers, crystallization, melting, and phase transition behaviors were explored using differential scanning calorimetry. With respect to the linear homopolymer, the incorporation of a trimethylsilyl group decreases the cooling crystallization temperature (Tc), whereas the presence of the long PEG grafts unexpectedly elevates Tc. For isothermal crystallization, a critical temperature was found at 70 °C, below which all polyethylene glycol-grafted butene-1 (PB-PEG) copolymers have faster crystallization kinetics than polybutene-1 (PB). The subsequent melting process shows that for the identical crystallization temperature, generated PB-PEG crystallites always have lower melting temperatures than that of PB. Moreover, the II-I phase transition behavior of copolymers is also dependent on the length of PEG grafts. When form II, obtained from isothermal crystallization at 60 °C, was annealed at 25 °C, PB-PEG-750, with the shortest PEG grafts of Mn = 750 g/mol, could have the faster transition rate than PB. However, PB-PEG-750 exhibits a negative correlation between transition rate and crystallization temperature. Differently, in PB-PEG copolymers with PEG grafts Mn = 2000 and 4000 g/mol, transition rates rise with elevating crystallization temperature, which is similar with homopolymer PB. Therefore, the grafting of the PEG side chain provides the available method to tune phase transition without sacrificing crystallization capability in butene-1 copolymers.