No abstract

Acquired chemotherapy resistance is one of the main culprits in the relapse of breast cancer. But the underlying mechanism of chemotherapy resistance remains elusive. Here, we demonstrate that a small adaptor protein, SH3BGRL, is not only elevated in the majority of breast cancer patients but also has relevance with the relapse and poor prognosis of breast cancer patients. Functionally, SH3BGRL upregulation enhances the chemoresistance of breast cancer cells to the first-line doxorubicin treatment through macroautophagic/autophagic protection. Mechanistically, SH3BGRL can unexpectedly bind to ribosomal subunits to enhance PIK3C3 translation efficiency and sustain ATG12 stability. Therefore, inhibition of autophagy or silence of PIK3C3 or ATG12 can effectively block the driving effect of SH3BGRL on doxorubicin resistance of breast cancer cells in vitro and in vivo. We also validate that SH3BGRL expression is positively correlated with that of PIK3C3 or ATG12, as well as the constitutive occurrence of autophagy in clinical breast cancer tissues. Taken together, our data reveal that SH3BGRL upregulation would be a key driver to the acquired chemotherapy resistance through autophagy enhancement in breast cancer while targeting SH3BGRL could be a potential therapeutic strategy against breast cancer. Abbreviations: ABCs: ATP-binding cassette transporters; Act D: actinomycin D; ACTB/β-actin: actin beta; ATG: autophagy-related; Baf A 1 : bafilomycin A 1 ; CASP3: caspase 3; CHX: cycloheximide; CQ: chloroquine; Dox: doxorubicin; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GEO: gene expression omnibus; GFP: green fluorescent protein; G6PD: glucose-6-phosphate dehydrogenase; GSEA: gene set enrichment analysis; IHC: immunochemistry; KEGG: Kyoto Encyclopedia of Genes and Genomes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; 3-MA: 3-methyladenine; mRNA: messenger RNA; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; SH3BGRL: SH3 domain binding glutamate-rich protein-like; SQSTM1/p62: sequestosome 1; ULK1: unc-51 like autophagy activating kinase 1

The issue of employee turnover is always critical for companies, and accurate predictions can help them prepare in time. Most past studies on employee turnover have focused on analyzing impact factors or using simple network centrality measures. In this paper, we study the problem from a completely new perspective by modeling users' historical job records as a dynamic bipartite graph. Specifically, we propose a bipartite graph embedding method with temporal information called dynamic bipartite graph embedding (DBGE) to learn the vector representation of employees and companies. Our approach not only considers the relations between employees and companies but also incorporates temporal information embedded in consecutive work records. We first define the Horary Random Walk on a bipartite graph to generate a sequence for each vertex in chronological order. Then, we employ the skip-gram model to obtain a temporal low-dimensional vector representation for each vertex and apply machine learning methods to predict employee turnover behavior by combining embedded features with employees' basic information. Experiments on a real-world dataset collected from one of China's largest online professional social networks show that the features learned through DBGE can significantly improve turnover prediction performance. Moreover, experiments on public Amazon and Taobao datasets show that our approach achieves better performance in the link prediction and visualization task than other graph embedding methods that do not consider temporal information. INDEX TERMS Graph embedding, employee turnover prediction, dynamic bipartite graph, horary random walk.

In recent years, the rapid development of China’s economy makes the existing building stock soaring, many of which have the service life of more than 10 years, thus emerging more and more hidden diseases, diseases and other quality problems urgently need to be reinforced. This paper around a multilayer cast-in-situ reinforced concrete frame structure of the old buildings, through the inspection process, the conclusion and the reinforcement scheme of combing the following conclusion: after old buildings reconstruction must be strictly according to the professional testing department of the appraisal report issued to reinforce the transformation processing, transformation of conditions in addition to meet the design requirements, the feasibility of economic cost should also be considered. The old buildings that cannot meet the above two basic conditions should not be changed or reinforced rashly.