Discovery of Novel Non-nucleoside DOT1L Inhibitors with Improved Pharmacokinetic Properties and Anti-lung Cancer Efficacy.

Given the considerable potential of DOT1L inhibitors in lung cancer therapy and the problematic pharmacokinetics of nucleoside inhibitors, our group launched a development program of non-nucleoside DOT1L inhibitors to improve the pharmacokinetic properties. Herein, two series of non-nucleoside compounds bearing piperidine or 3-(aminomethyl)pyrrolidin-3-ol as "ribose mimics" were designed and evaluated through antiproliferation assay and western blot analysis. The optimal inhibited the proliferation of H460 cells with an IC value of 2.

Uneven Strain Distribution Induces Consecutive Dislocation Slipping, Plane Gliding, and Subsequent Detwinning of Penta-Twinned Nanoparticles.

Twin structures possess distinct physical and chemical properties by virtue of their specific twin configuration. However, twinning and detwinning processes are not fully understood on the atomic scale. Integrating high resolution transmission electron microscopy and molecular dynamic simulations, we find tensile strain in the asymmetrical 5-fold twins of Au nanoparticles leads to twin boundary migration through dislocation sliding (slipping of an atomic layer) along twin boundaries and dislocation reactions at the 5-fold axis under an electron beam.

Structure-guided design of potent JAK1-selective inhibitors based on 4-amino-7H-pyrrolo[2,3-d]pyrimidine with anti-inflammatory efficacy.

In a continuous effort to develop Janus kinase 1 (JAK1)-selective inhibitors, a novel series of 4-amino-7H-pyrrolo[2,3-d]pyrimidine derivatives bearing the piperidinyl fragment were designed and synthesized according to a combination strategy. Through enzymatic assessments, the superior compound 12a with an IC value of 12.6 nM against JAK1 was identified and a 10.

Diffusion growth mechanism of penta-twinned Ag nanocrystals from decahedral seeds.

Crystals with penta-twinned structures can be produced from diverse fcc metals, but the mechanisms that control the final product shapes are still not well understood. By using the theory of absorbing Markov chains to account for the growth of penta-twinned decahedral seeds via atom deposition and surface diffusion, we predicted the formation of various types of products: decahedra, nanorods, and nanowires. We showed that the type of product depends on the morphology of the seed and that small differences between various seed morphologies can lead to significantly different products.

MLRD-Net: 3D multiscale local cross-channel residual denoising network for MRI-based brain tumor segmentation.

The precise segmentation of multimodal MRI images is the primary stage of tumor diagnosis and treatment. Current segmentation strategies often underutilize multiscale features, which can easily lead to loss of contextual information, reduction of low-level features and noise interference. To overcome these issues, a 3D multiscale local cross-channel residual denoising network (MLRD-Net) for an MRI-based brain tumor segmentation algorithm is proposed in this paper.

OptiBoost: A method for choosing a safe and efficient boost for the bond-boost method in accelerated molecular dynamics simulations with hyperdynamics.

Accelerated molecular-dynamics (MD) simulations based on hyperdynamics (HD) can significantly improve the efficiency of MD simulations of condensed-phase systems that evolve via rare events. However, such simulations are not generally easy to apply since appropriate boosts are usually unknown. In this work, we developed a method called OptiBoost to adjust the value of the boost in HD simulations based on the bond-boost method.

Solution-Phase Growth of Cu Nanowires with Aspect Ratios Greater Than 1000: Multiscale Theory.

Penta-twinned metal nanowires are finding widespread application in existing and emerging technologies. However, little is known about their growth mechanisms. We probe the origins of chloride- and alkylamine-mediated, solution-phase growth of penta-twinned Cu nanowires from first-principles using multiscale theory.

DLSTM-Based Successive Cancellation Flipping Decoder for Short Polar Codes.

Polar code has been adopted as the control channel coding scheme for the fifth generation (5G), and the performance of short polar codes is receiving intensive attention. The successive cancellation flipping (SC flipping) algorithm suffers a significant performance loss in short block lengths. To address this issue, we propose a double long short-term memory (DLSTM) neural network to locate the first error bit.

Extrapolating microdomain Ca(2+) dynamics using BK channels as a Ca(2+) sensor.

Ca(2+) ions play crucial roles in mediating physiological and pathophysiological processes, yet Ca(2+) dynamics local to the Ca(2+) source, either from influx via calcium permeable ion channels on plasmic membrane or release from internal Ca(2+) stores, is difficult to delineate. Large-conductance calcium-activated K(+) (BK-type) channels, abundantly distribute in excitable cells and often localize to the proximity of voltage-gated Ca(2+) channels (VGCCs), spatially enabling the coupling of the intracellular Ca(2+) signal to the channel gating to regulate membrane excitability and spike firing patterns. Here we utilized the sensitivity and dynamic range of BK to explore non-uniform Ca(2+) local transients in the microdomain of VGCCs.