A van der Waals density functional theory study of poly(vinylidene difluoride) crystalline phases.

The structure and energetics of crystalline phases of poly(vinylidene difluoride) were investigated using density functional theory (DFT). In particular, we present data on non-polar analogues of the β and γ phases that have not yet been experimentally characterised. The results from a variety of exchange and correlation functionals were compared and it was found that van der Waals (vdW) interactions have an important effect on the calculated crystal structures. While the relative phase energies were not strongly dependent on the functional, the cohesive energies were significantly affected.

Innovative high-content screening platform identified N -(2-butoxyphenyl)-3-(phenyl)acrylamides as novel antifibrotics.

Fibrogenic processes instigate fatal chronic diseases leading to organ failure and death. Underlying biological processes involve induced massive deposition of extracellular matrix (ECM) by aberrant fibroblasts. We subjected diseased primary human lung fibroblasts to an advanced three-dimensional phenotypic high-content assay and screened a repurposing drug library of small molecules for inhibiting ECM deposition. Fibrotic Pattern Detection by Artificial Intelligence identified tranilast as an effective inhibitor. Structure-activity relationship studies confirmed N-(2-butoxyphenyl)-3-(phenyl)acrylamides (N23Ps) as a novel and highly potent compound class. N23Ps suppressed myofibroblast transdifferentiation, ECM deposition, cellular contractility, and altered cell shapes, thus advocating a unique mode of action. Mechanistically, transcriptomics identified SMURF2 as a potential therapeutic target network. Antifibrotic activity of N23Ps was verified by proteomics in a human ex vivo tissue fibrosis disease model, suppressing profibrotic markers SERPINE1 and CXCL8. Conclusively, N23Ps are a novel class of highly potent compounds inhibiting organ fibrosis in patients.

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