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Chemistry - a European journal e202200496 (2022). doi:10.1002/chem.202200496, Published by Wiley-VCH, Weinheim

Some rare indigo derivatives have been known for a long time to be photochromic upon irradiation with red light, which should be advantageous for many applications. However, the absence of strategies to tune their thermal half-lives by modular molecular design as well as the lack of proper synthetic methods to prepare a variety of such molecules from the parent indigo dye have so far precluded their use. In this work, several synthetic protocols for N-functionalization have been developed, and a variety of N-alkyl and N-aryl indigo derivatives have been prepared. By installation of electron-withdrawing substituents on the N-aryl moieties, the thermal stability of the Z-isomers could be enhanced while maintaining the advantageous photoswitching properties upon irradiation with red light (660 nm LED). Both experimental data and computational results suggest that the ability to tune thermal stability without affecting the dyes' absorption maxima originates from the twisted geometry of the N-aryl groups. The new indigo photoswitches reported are expected to have a large impact on the development of optical methods and applications in both life and material sciences.

A Ni-catalyzed reductive cross-coupling of styrenyl aziridines with aryl iodides is reported. This reaction proceeds by a stereoconvergent mechanism and is thus amenable to asymmetric catalysis using a chiral bioxazoline ligand for Ni. The process allows facile access to highly enantioenriched 2-arylphenethylamines from racemic aziridines. Multivariate analysis revealed that ligand polarizability, among other features, influences the observed enantioselectivity, shedding light on the success of this emerging ligand class for enantioselective Ni catalysis.

A Ni-catalyzed Negishi cross-coupling with 1,1-disubstituted styrenyl aziridines has been developed. This method delivers valuable β-substituted phenethylamines via a challenging reductive elimination that affords a quaternary carbon. A novel electron-deficient olefin ligand, Fro-DO, proved crucial for achieving high rates and chemoselectivity for C-C bond formation over β-H elimination. This ligand is easy to access, is stable, and presents a modular framework for reaction discovery and optimization. We expect that these attributes, combined with the fact that the ligands impart distinct electronic properties to a metal, will support the invention of new transformations not previously possible using established ligands.

Deep learning models such as convolutional neural net- work have been widely used in 3D biomedical segmentation and achieve state-of-the-art performance. However, most of them often adapt a single modality or stack multiple modalities as different input channels. To better leverage the multi- modalities, we propose a deep encoder-decoder structure with cross-modality convolution layers to incorporate different modalities of MRI data. In addition, we exploit convolutional LSTM to model a sequence of 2D slices, and jointly learn the multi-modalities and convolutional LSTM in an end-to-end manner. To avoid converging to the certain labels, we adopt a re-weighting scheme and two-phase training to handle the label imbalance. Experimental results on BRATS-2015 show that our method outperforms state-of-the-art biomedical segmentation approaches., CVPR 2017

A Ni-catalyzed Negishi cross-coupling with 1,1-disubstituted styrenyl aziridines has been developed. This method delivers valuable β-substituted phenethylamines via a challenging reductive elimination that affords a quaternary carbon. A novel electron-deficient olefin ligand, Fro-DO, proved crucial for achieving high rates and chemoselectivity for C–C bond formation over β-H elimination. This ligand is easy to access, is stable, and presents a modular framework for reaction discovery and optimization. We expect that these attributes, combined with the fact that the ligands impart distinct electronic properties to a metal, will support the invention of new transformations not previously possible using established ligands.

Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX) from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA), a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4.