Synthetic Sample Selection via Reinforcement Learning

Synthesizing realistic medical images provides a feasible solution to the shortage of training data in deep learning based medical image recognition systems. However, the quality control of synthetic images for data augmentation purposes is under-investigated, and some of the generated images are not realistic and may contain misleading features that distort data distribution when mixed with real images. Thus, the effectiveness of those synthetic images in medical image recognition systems cannot be guaranteed when they are being added randomly without quality assurance. In this work, we propose a reinforcement learning (RL) based synthetic sample selection method that learns to choose synthetic images containing reliable and informative features. A transformer based controller is trained via proximal policy optimization (PPO) using the validation classification accuracy as the reward. The selected images are mixed with the original training data for improved training of image recognition systems. To validate our method, we take the pathology image recognition as an example and conduct extensive experiments on two histopathology image datasets. In experiments on a cervical dataset and a lymph node dataset, the image classification performance is improved by 8.1% and 2.3%, respectively, when utilizing high-quality synthetic images selected by our RL framework. Our proposed synthetic sample selection method is general and has great potential to boost the performance of various medical image recognition systems given limited annotation.Comment: MICCAI202

AS1411-Induced Growth Inhibition of Glioma Cells by Up-Regulation of p53 and Down-Regulation of Bcl-2 and Akt1 via Nucleolin

AS1411 binds nucleolin (NCL) and is the first oligodeoxynucleotide aptamer to reach phase I and II clinical trials for the treatment of several cancers. However, the mechanisms by which AS1411 targets and kills glioma cells and tissues remain unclear. Here we report that AS1411 induces cell apoptosis and cycle arrest, and inhibits cell viability by up-regulation of p53 and down-regulation of Bcl-2 and Akt1 in human glioma cells. NCL was overexpressed in both nucleus and cytoplasm in human glioma U87, U251 and SHG44 cells compared to normal human astrocytes (NHA). AS1411 bound NCL and inhibited the proliferation of glioma cells but not NHA, which was accompanied with up-regulation of p53 and down-regulation of Bcl-2 and Akt1. Moreover, AS1411 treatment resulted in the G2/M cell cycle arrest in glioma cells, which was however abolished by overexpression of NCL. Further, AS1411 induced cell apoptosis, which was prevented by silencing of p53 and overexpression of Bcl-2. In addition, AS1411 inhibited the migration and invasion of glioma cells in an Akt1-dependent manner. Importantly, AS1411 inhibited the growth of glioma xenograft and prolonged the survival time of glioma tumor-bearing mice. These results revealed a promising treatment of glioma by oligodeoxynucleotide aptamer

Determinants that control the specific interactions between TAB1 and p38α

Previous studies have revealed that transforming growth factor-beta-activated protein kinase 1 (TAB1) interacts with p38 alpha and induces p38 alpha autophosphorylation. Here, we examine the sequence requirements in TAB1 and p38 alpha that drive their interaction. Deletion and point mutations in TAB1 reveal that a proline residue in the C terminus of TAB1 (Pro412) is necessary for its interaction with p38 alpha. Furthermore, a cryptic D-domain-like docking site was identified adjacent to the N terminus of Pro412, putting Pro412 in the (phi(B)+3 position of the docking site. Through mutational analysis, we found that the previously identified hydrophobic docking groove in p38 alpha is involved in this interaction, whereas the CD domain and ED domain are not. Furthermore, chimeric analysis with p38 beta (which does not bind to TAB1) revealed a previously unidentified locus of p38 alpha comprising Thr218 and Ile275 that is essential for specific binding of p38 alpha to TAB1. Converting either of these residues to the corresponding amino acid of p380 abolishes p38 alpha interaction with TAB1. These p38a mutants still can be fully activated by p38 alpha upstream activating kinase mitogen-activated protein kinase kinase 6, but their basal activity and activation in response to some extracellular stimuli are reduced. Adjacent to Thr218 and Ile275 is a site where large conformational changes occur in the presence of docking-site peptides derived from p38 alpha substrates and activators. This suggests that TAB1-induced autophosphorylation of p38 alpha results from conformational changes that are similar but unique to those seen in p38 alpha interactions with its substrates and activating kinases

ChIP-seq and Functional Analysis of the SOX2 Gene in Colorectal Cancers

SOX2 is anHMGbox containing transcription factor that has been implicated in various types of cancer, but its role in colorectal cancers (CRC) has not been studied. Here we show that SOX2 is overexpressed in CRC tissues compared with normal adjacent tissues using immunohistochemical staining and RT-PCR. We also observed an increased SOX2 expression in nucleus of colorectal cancer tissues (46%, 14/30 cases vs. 7%, 2/30 adjacent tissues). Furthermore, knockdown of SOX2 in SW620 colorectal cancer cells decreased their growth rates in vitro cell line, and in vivo in xenograft models. ChIP-Seq analysis of SOX2 revealed a consensus sequence of wwTGywTT. An integrated expression profiling and ChIP-seq analysis show that SOX2 is involved in the BMP signaling pathway, steroid metabolic process, histone modifications, and many receptor-mediated signaling pathways such as IGF1R and ITPR2 (Inositol 1,4,5-triphosphate receptor, type 2).MOST, Chin

Axin determines cell fate by controlling the p53 activation threshold after DNA damage

Cells can undergo either cell-cycle arrest or apoptosis after genotoxic stress, based on p53 activity(1-6). Here we show that cellular fate commitment depends on Axin forming distinct complexes with Pirh2, Tip60, HIPK2 and p53. In cells treated with sublethal doses of ultra-violet (UV) radiation or doxorubicin (Dox), Pirh2 abrogates Axin-induced p53 phosphorylation at Ser 46 catalysed by HIPK2, by competing with HIPK2 for binding to Axin. However, on lethal treatment, Tip60 interacts with Axin and abrogates Pirh2-Axin binding, forming an Axin-Tip60-HIPK2-p53 complex that allows maximal p53 activation to trigger apoptosis. We also provide evidence that the ATM/ATR pathway mediates the Axin-Tip60 complex assembly. An axin mutation promotes carcinogenesis in Axin(Fu)/+ (Axin-Fused) mice, consistent with a dominant-negative role for Axin(Fu) in p53 activation. Thus, Axin is a critical determinant in p53-dependent tumour suppression in which Pirh2 and Tip60 have different roles in triggering cell-cycle arrest or apoptosis depending on the severity of genotoxic stress.973 Program and 863 Program National Natural Science Foundation of China Ministry of Education of China National Basic Research Program of the Ministry of Science and Technology National Science Foundation of Fujian Provinc

ULK1/2所构成的信号节点除控制细胞自噬外还控制葡萄糖代谢通路

文章简介在细胞感受到环境中营养物质和生长因子的提供量发生改变后,代谢通路的重编程对于维持此时胞内的稳态是非常重要的过程。ULK1和ULK2是传递外界应激信号至自噬发生的重要整合因子。本项研究发现,在缺少氨基酸和生长因子时,ULK1/2能直接磷酸化多个糖酵解相关的酶,包括己糖激酶(HK)、国家自然科学基金重点项目；国家科技部(973课题)；国家基础科学人才培养基金等的经费支持