Abstract-Peroxisome proliferator-activated receptor ␤/␦ (PPAR␤/␦) is an essential transcription factor in myocardial metabolism. This study aims to investigate the effects of PPAR␤/␦ activation in the adult heart on mitochondrial biology and oxidative metabolism under normal and pressure-overload conditions. We have investigated the effects of cardiac constitutively active PPAR␤/␦ in adult mice using a tamoxifen-inducible transgenic approach with Cre-LoxP recombination. The expression of PPAR␤/␦ mRNA and protein in cardiomyocytes of adult mice was substantially increased after short-term induction. In these mice, the cardiac expression of key factors involved in mitochondrial biogenesis, such as PPAR␥ coactivator-1, endogenous antioxidants Cu/Zn superoxide dismutase, and catalase, fatty acid, and glucose metabolism, such as carnitine palmitoyltransferase Ib, carnitine palmitoyltransferase II, and glucose transporter 4, were upregulated. Subsequently, myocardial oxidative metabolism was elevated concomitant with an increased mitochondrial DNA copy number and an enhanced cardiac performance. Moreover, activation of PPAR␤/␦ in the adult heart improved cardiac function and resisted progression to pathological development in mechanical stress condition. We conclude that PPAR␤/␦ activation in the adult heart will promote cardiac performance along with transcriptional upregulation of mitochondrial biogenesis and defense, as well as oxidative metabolism at basal and pressure-overload conditions. (Hypertension. 2011;57:223-230.) • Online Data Supplement

With the development of the IoT technology, an unprecedented number of IoT terminals are connected to various networks. Commercial-off-the-shelf (COTS) technology is widely used in the IoT terminal firmware, which results in high code reuse rates. Such firmware is always heterogeneous and closedsource. It is so difficult to detect and investigate the security risks at the firmware level that their impacts are faster and broader. In recent years, some firmware security detection technologies based on similarity are gradually becoming a research hotspot. However, in these studies, the basic issue regarding whether these foundations comprise an essential basis for comparison and their utility as similarity measures has not been addressed theoretically. Inspired by biological genes, this paper attempts to supplement a foundation for cross-platform firmware binary code homology and similarity analysis by mining firmware code genes that can essentially identify code and exhibit stability, antivariability and heritability. The firmware code gene extract system(FCGES) is designed and implemented in this paper. FCGES first extracts the features of firmware code, then numericizes and normalizes them, and finally sublimates them to firmware code genes by the hypothesis margin. The experimental results show that the firmware code gene extracted by FCGES has essentiality, stability, antivariability and heritability on different platforms.

We aimed to investigate the pattern of expression and clinical significance of isocitrate dehydrogenase 1(IDH1) in esophageal squamous cell carcinoma (ESCC). The IDH1 expression was determined by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis using 38 pairs of frozen tissues. Enzyme-linked immunosorbent assay was employed to measure 67 pairs of serum samples from patients and their controls to evaluate its diagnostic value. Immunohistochemistry analysis of 111 formalin-fixed paraffin embedded tissue samples was conducted for explaining its prognostic value. After shRNA transfection, CCK8 and clonal efficiency assays were carried on for verifying the function of IDH1 in vitro. Increased expression at mRNA (P < 0.001) and protein levels (immunohistochemistry: P < 0.001, Western blot analysis: P < 0.001) were observed. Similarly, the IDH1 expression in serum from patients with ESCC was significantly upregulated relative to that from healthy controls (P < 0.001). Kaplan–Meier curve indicated that IDH1 upregulation predicted worse overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses identified IDH1 expression as an independent prognostic factor for OS and PFS. Furthermore, OD450 values and colony numbers were decreased in sh-IDH1 groups (all P < 0.05). In conclusion, IDH1 is upregulated in patients with ESCC and can be used as a good potential biomarker for diagnosis and prognosis.

We aimed to examine Notch2 expression in oesophageal squamous cell carcinoma (ESCC) patients and to evaluate its prognostic potential. Immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were utilized to investigate the Notch2 expression status and prognostic value. Furtherly, CCK8 and clonogenic assays were conducted to determine if Notch2 inhibition by shRNA could lead to a decrease in the proliferation and survival of ESCC cells. A notably higher Notch2 expression level was found in ESCC tissues at the mRNA (P < 0.0001) and protein levels (IHC: P = 0.004; western blot: P = 0.021). Log-rank analysis demonstrated that Notch2 overexpression was significantly associated with worse overall survival (OS) (29.1% vs. 49.1%; P = 0.013) and progression-free survival (PFS) (15.3% vs. 34.4%; P = 0.006) rates in ESCC patients. The multivariate analysis revealed Notch2 as an independent prognostic factor for OS and PFS (P = 0.002 and 0.006, resp.). Besides, in vitro assays showed that OD450 values and colony formations were significantly reduced in Notch2-shRNA group (all P < 0.0001). In conclusion, these results show that Notch2 is up-regulated in ESCC tissues and could serve as a promising biomarker for identifying individuals with poor prognostic potential.

Up to now, the prognosis of non-small cell lung cancer (NSCLC) is poor. With progress of cancer biology, a number of genes have been investigated for predicting prognosis of NSCLC, such as cancer stem cell markers SRY (sex determining region Y)-box 2 (SOX2) and Nestin. Recently, a series of studies have been performed to examine the associations of SOX2 and Nestin with clinical parameters and prognosis in NSCLC, however, the results were not consistent. In the present study, we conducted a systematic review and meta-analysis to summarize the associations. Four English databases (PubMed, ISI web of science, Embase, and Ovid) were used to search the relevant studies with the last date of November 10, 2015. The pooling analyses were stratified by DNA amplification and protein expression. The pooling ORs or HRs were used to assess the strength of the associations. Finally, we included 19 articles for SOX2 and six articles for Nestin according to the inclusion and exclusion criteria. The pooling analyses revealed that there were significant associations between SOX2 DNA amplification and clinical features of NSCLC, gender, smoking status, squamous cell cancer (SCC) histology, and differentiations. And significant associations were also identified between SOX2 protein expression and clinical parameters, smoking status and SCC histology. For Nestin, its protein expression was correlated with lymph node metastasis and stage. Simultaneously, we found that high/positive SOX2 alterations, either DNA amplification or protein expression, were favorable for overall survival (OS) in NSCLC. On the contrary, high/positive Nestin protein expression was poor for OS.

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We aimed to value the diagnostic potential of serum miR-1297 in esophageal squamous cell cancer (ESCC). Its expression level was detected in 156 pairs of patients with ESCC and healthy volunteers using quantitative real-time polymerase chain reaction (qRT-PCR) method. It was statistically decreased in ESCC patients compared with healthy controls. AUC based on serum miR-1297 was 0.840 ± 0.035 in discovery group and 0.837 ± 0.034 in validation group. Further analysis on early-stage patients revealed that the AUC was 0.819 ± 0.053 in discovery group and 0.814 ± 0.044 in validation group. Its sensitivity and specificity were promising. In conclusion, serum miR-1297 can serve as an ideal indicator for the diagnosis of ESCC.

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