Simvastatin Sensitizes Radioresistant Prostate Cancer Cells by Compromising DNA Double-Strand Break Repair.

Prostate cancer (PCa) is one of the most prevalent male cancers in western world. Radiation therapy (RT) is commonly used to treat PCa patients. However, a certain proportion of patients develop radioresistant PCa cells, which results in metastatic disease. Statins, which inhibit 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, are commonly used to treat hypercholesterolemia, exhibiting beneficial effects on cardiovascular diseases and on several types of cancers, including PCa. However, the mechanistic details and crosstalk between statins and RT in PCa cells remain unknown. In this study, radioresistant DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells were used to evaluate whether simvastatin could enhance the effect of ionizing radiation (IR). The crucial molecules that associated with simvastatin elevated radiosensitivity in PCa cells were explored. Our results demonstrated that a combination treatment with simvastatin and IR synergistically induced apoptosis of radioresistant PCa cells. In addition, simvastatin appeared to compromise DNA double-strand breaks repair by activating the expressions of histone 2A family member X (γ-H2AX) and phospho-checkpoint kinase 1 (p-CHK1), suggesting an underlying mechanism for this radiosensitization of PCa cells. These findings reveal that simvastatin may be a potent therapeutic agent for co-treatment with radiation to overcome radioresistance in PCa cells.

Design of Wearable Breathing Sound Monitoring System for Real-Time Wheeze Detection.

In the clinic, the wheezing sound is usually considered as an indicator symptom to reflect the degree of airway obstruction. The auscultation approach is the most common way to diagnose wheezing sounds, but it subjectively depends on the experience of the physician. Several previous studies attempted to extract the features of breathing sounds to detect wheezing sounds automatically. However, there is still a lack of suitable monitoring systems for real-time wheeze detection in daily life. In this study, a wearable and wireless breathing sound monitoring system for real-time wheeze detection was proposed. Moreover, a breathing sounds analysis algorithm was designed to continuously extract and analyze the features of breathing sounds to provide the objectively quantitative information of breathing sounds to professional physicians. Here, normalized spectral integration (NSI) was also designed and applied in wheeze detection. The proposed algorithm required only short-term data of breathing sounds and lower computational complexity to perform real-time wheeze detection, and is suitable to be implemented in a commercial portable device, which contains relatively low computing power and memory. From the experimental results, the proposed system could provide good performance on wheeze detection exactly and might be a useful assisting tool for analysis of breathing sounds in clinical diagnosis.

Transcriptional control of genes involved in yeast phospholipid biosynthesis.

Phospholipid biosynthetic genes encode enzymes responsible for phospholipid biosynthesis. They are coordinately regulated by the availability of phospholipid precursors through the inositol-sensitive upstream activating sequence (UAS(INO)). However, not all phospholipid genes are UAS(INO)-containing genes and not all UAS(INO)-containing genes have the same response to the phospholipid precursors. Therefore, the transcriptional regulation of phospholipid genes in response to the availability of phospholipid precursors is still unclear. Here, 22 out of 47 phospholipid biosynthetic genes were identified as UAS(INO)-containing genes, including EKI1, EPT1, INM1, IPK2, KCS1, PAH1, and PIK1 which have never been reported before. We also showed, using qRT-PCR technique, that 12 UAS(INO)-containing genes are down-regulated by 100 µM inositol in the wild type cells and up-regulated by 100 µM inositol in the ino2Δ cells. Therefore, it is possible that these genes are transcriptionally regulated by the UAS(INO) through the negative response of Ino2p to inositol. One other UAS(INO)-containing gene might be regulated by the positive response of Ino2p to 100 µM inositol. Surprisingly, we found 9 UAS(INO)-containing genes are not dependent on the response of Ino2p to 100 µM inositol, indicating that they may be regulated by other pathway. Furthermore, we identified 9 and 3 non-UAS(INO)-containing genes that are possibly regulated by the negative and positive response of Ino2p to 100 µM inositol, respectively. Therefore, these observations provide insight into the understanding of the co-regulated phospholipid biosynthetic genes expression.

Experimental investigation of the reliability issue of RRAM based on high resistance state conduction.

In this paper, reliability issues of robust HfO(x)-based RRAM are experimentally investigated in terms of cycling ageing, temperature impact and voltage acceleration. All reliability issues can be estimated by the conduction of the high resistance state (HRS). The conduction current of the HRS exponentially increases as the square root of the applied voltage, which is well explained by 'quasi-Poole-Frenkel-type' trap assistant tunneling. Further experiments on HRS conduction at different temperatures show that the depth of the potential well of the trap in HfO(x) film is about 0.31 eV. The degradation induced by the cycling ageing is possibly ascribed to the increase of the amount of oxygen ions in the TiO(x) layer of the TiN/TiO(x)/HfO(x)/TiN device. The retention times with various stress voltages at different temperatures also exhibit an exponential relationship to the square root of the applied voltage, indicating that stress current plays a dominant role for the degradation of the HRS. An oxygen-release model is proposed to explain the relationship of retention time to HRS conduction current.