LncRNA-p21 alters the antiandrogen enzalutamide-induced prostate cancer neuroendocrine differentiation via modulating the EZH2/STAT3 signaling

While the antiandrogen enzalutamide (Enz) extends the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might also result in some adverse effects via inducing the neuroendocrine differentiation (NED). Here we found that lncRNA-p21 is highly expressed in the NEPC patients derived xenograft tissues (NEPC-PDX). Results from cell lines and human clinical sample surveys also revealed that lncRNA-p21 expression is up-regulated in NEPC and Enz treatment could increase the lncRNA-p21 to induce the NED. Mechanism dissection revealed that Enz could promote the lncRNA-p21 transcription via altering the androgen receptor (AR) binding to different androgen-response-elements, which switch the EZH2 function from histone-methyltransferase to non-histone methyltransferase, consequently methylating the STAT3 to promote the NED. Preclinical studies using the PDX mouse model proved that EZH2 inhibitor could block the Enz-induced NED. Together, these results suggest targeting the Enz/AR/lncRNA-p21/EZH2/STAT3 signaling may help urologists to develop a treatment for better suppression of the human CRPC progression

Copper Metal for Semiconductor Interconnects

Resistance-capacitance (RC) delay produced by the interconnects limits the speed of the integrated circuits from 0.25 mm technology node. Copper (Cu) had been used to replace aluminum (Al) as an interconnecting conductor in order to reduce the resistance. In this chapter, the deposition method of Cu films and the interconnect fabrication with Cu metallization are introduced. The resulting integration and reliability challenges are addressed as well

Role of exosomes in hepatocellular carcinoma and the regulation of traditional Chinese medicine

Hepatocellular carcinoma (HCC) usually occurs on the basis of chronic liver inflammatory diseases and cirrhosis. The liver microenvironment plays a vital role in the tumor initiation and progression. Exosomes, which are nanometer-sized membrane vesicles are secreted by a number of cell types. Exosomes carry multiple proteins, DNAs and various forms of RNA, and are mediators of cell-cell communication and regulate the tumor microenvironment. In the recent decade, many studies have demonstrated that exosomes are involved in the communication between HCC cells and the stromal cells, including endothelial cells, macrophages, hepatic stellate cells and the immune cells, and serve as a regulator in the tumor proliferation and metastasis, immune evasion and immunotherapy. In addition, exosomes can also be used for the diagnosis and treatment HCC. They can potentially serve as specific biomarkers for early diagnosis and drug delivery vehicles of HCC. Chinese herbal medicine, which is widely used in the prevention and treatment of HCC in China, may regulate the release of exosomes and exosomes-mediated intercellular communication. In this review, we summarized the latest progresses on the role of the exosomes in the initiation, progression and treatment of HCC and the potential value of Traditional Chinese medicine in exosomes-mediated biological behaviors of HCC

Reproducibility studies on OCT rapid and repeated scanning method for the diagnosis of glaucoma

AIM: To evaluate the application ofoptical coherence tomography(OCT)and retinal nerve fiber layer thickness(RNFL)measured by rapid and repeated methods in the diagnosis of glaucoma repeated significance. <p>METHODS: Stratus OCT were measured in 38 normal subjects and 42 patients with the primary RNFL thickness of open angle glaucoma patients. Rapid and repeated scanning was applied respectively to measure the RNFL thickness of patients with normal and primary open angle glaucoma. The average RNFL thickness's related coefficient and various coefficient of the temporal, upper, lower and nasal region made reproducibility assessment. <p>RESULTS: In normal and primary open angle glaucoma patients, the overall average RNFL thickness and lateral temporal, above, nasal, below RNFL thickness, in which two groups did not show differences; repeated scanning average RNFL thickness was measured in fast scanning scheme around the optic disc, and had higher ICC and lower value of CV, there were significant differences in the temporal region(<i>P</i>=0.042). The temporal, nasal, upper and lower area of the retinal nerve fiber layer thickness of the ICC(CV)values were as follows: fast scan was 0.918(7.2%), 0.831(6.82%), 0.856(5.12%), 0.911(7.19%); repeated scans were 0.927(3.21%), 0.962(5.01%), 0.909(6.02%), 0.869(4.67%), 0.918(6.89%).<p>CONCLUSION: In normal subjects and patients with primary open angle glaucoma, the application of rapid and repeated scanning in measurement of RNFL with OCT thickness has repeated significance, but repeated scanning scheme in the assessment of RNFL thickness is more accurate

Friend Ranking in Online Games via Pre-training Edge Transformers

Friend recall is an important way to improve Daily Active Users (DAU) in online games. The problem is to generate a proper lost friend ranking list essentially. Traditional friend recall methods focus on rules like friend intimacy or training a classifier for predicting lost players' return probability, but ignore feature information of (active) players and historical friend recall events. In this work, we treat friend recall as a link prediction problem and explore several link prediction methods which can use features of both active and lost players, as well as historical events. Furthermore, we propose a novel Edge Transformer model and pre-train the model via masked auto-encoders. Our method achieves state-of-the-art results in the offline experiments and online A/B Tests of three Tencent games.Comment: Accepted by the 46th International ACM SIGIR Conference on Research and Development in Information Retrieval (SIGIR 2023