A Novel Feeder Link Handover Strategy for Backhaul in LEO Satellite Networks.

Thanks to their wide coverage and relatively low latency compared to geosynchronous satellites, Low Earth Orbit (LEO) satellite networks have been regarded as one of the most promising solutions to provide global broadband backhaul for mobile users and IoT devices. In LEO satellite networks, the frequent feeder link handover invokes unacceptable communication interruptions and affects the backhaul quality. To overcome this challenge, we propose a maximum backhaul capacity handover strategy for feeder links in LEO satellite networks. To improve the backhaul capacity, we design an available backhaul capacity ratio to jointly consider feeder link quality and the inter-satellite network in handover decisions. In addition, we introduce a service time factor and handover control factor to reduce the handover frequency. Then, we propose the handover utility function based on the designed handover factors and propose a greedy-based handover strategy. Simulation results show that the proposed strategy outperforms conventional handover strategies in backhaul capacity with low handover frequency.

A cyclic peptide retards the proliferation of DU145 prostate cancer cells in vitro and in vivo through inhibition of FGFR2.

In malignancies, fibroblast growth factor receptors (FGFRs) signaling is reinforced through overexpression of fibroblast growth factors (FGFs) or their receptors. FGFR2 has been proposed as a target for cancer therapy, because both the expression and activation of FGFR2 are boosted in various malignant carcinomas. Although several chemicals have been designed against FGFR2, they did not exhibit enough specificity and might bring potential accumulated toxicity. In this study, we developed an epitope peptide (P5) and its cyclic derivative (DcP5) based on the structure of FGF2 to limit the activation of FGFR2. The anticancer activities of P5 and DcP5 were examined in vitro and in vivo. Our results demonstrated that P5 significantly inhibited the cell proliferation in FGFR2-dependent manner in DU145 cells and retarded tumor growth in DU145 xenograft model with negligible toxicity toward normal organs. Further investigations found that the Gln4 and Glu6 residues of P5 bind to FGFR2 to abolish its activation. Moreover, we developed the P5 cyclic derivative, DcP5, which achieved reinforced stability and anticancer activity in vivo. Our findings suggest P5 and its cyclic derivative DcP5 as potential candidates for anticancer therapy.

Three surgical planes identified in laparoscopic complete mesocolic excision for right-sided colon cancer.

BACKGROUND: Complete mesocolic excision provides a correct anatomical plane for colon cancer surgery. However, manifestation of the surgical plane during laparoscopic complete mesocolic excision versus in computed tomography images remains to be examined. METHODS: Patients who underwent laparoscopic complete mesocolic excision for right-sided colon cancer underwent an abdominal computed tomography scan. The spatial relationship of the intraoperative surgical planes were examined, and then computed tomography reconstruction methods were applied. The resulting images were analyzed. RESULTS: In 44 right-sided colon cancer patients, the surgical plane for laparoscopic complete mesocolic excision was found to be composed of three surgical planes that were identified by computed tomography imaging with cross-sectional multiplanar reconstruction, maximum intensity projection, and volume reconstruction. For the operations performed, the mean bleeding volume was 73±32.3 ml and the mean number of harvested lymph nodes was 22±9.7. The follow-up period ranged from 6-40 months (mean 21.2), and only two patients had distant metastases. CONCLUSIONS: The laparoscopic complete mesocolic excision surgical plane for right-sided colon cancer is composed of three surgical planes. When these surgical planes were identified, laparoscopic complete mesocolic excision was a safe and effective procedure for the resection of colon cancer.

Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance.

Twist1 is a highly conserved basic helix-loophelix transcription factor, and has been shown to play an important role in carcinogenesis of many tumors including colorectal cancer (CRC). Here we aimed to investigate the role of Twist1 in the clinical significance and chemoresistance in CRC. In this study, we examined the correlation between Twist1 expression and clinicopathological characteristics using immunohistochemistry in patients with CRC. The molecular mechanisms of Twist1 expression and its effects on chemosensitivity to 5-Fluorouracil and oxaliplatin were also explored by MTT assay, colony forming assay, flow cytometry assay. The results indicate that Twist1 is overexpressed in cancer tissue, and its positive expression are related to histological grade (P=0.004), T-stage (P=0.033), N-stage (P=0.000), M-stage (P=0.040), TNM stage (P=0.002) and recurrence (P=0.023). Moreover, positive Twist1 expression is correlated with poor overall survival in CRC patients (P<0.0001), and is a significant independent prognostic indicator. In addition, we show that knockdown of Twist1 inhibits proliferation, and increased the percentage of apoptotic cells of CRC cell lines. Our findings suggest that Twist1 promotes proliferation and chemoresistance of CRC cells. Twist1 may be a potential prognostic marker and a molecular target for therapies.

Alisertib Induces Cell Cycle Arrest, Apoptosis, Autophagy and Suppresses EMT in HT29 and Caco-2 Cells.

Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G2/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5' AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells.

Biphasic Regulation of Lipid Metabolism: A Meta-Analysis of Icodextrin in Peritoneal Dialysis.

OBJECTIVES: The objective of this systematic meta-analysis was to study the impact of icodextrin (ICO) on lipid profiles. METHODS: MEDLINE, PubMed, Embase, Chinese Biomedical Literature, and the Cochrane Library and Reference lists were searched (last search September 2014) in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Searches identified 13 eligible trials with a total of 850 patients. The differentials of total cholesterol (TC) and free fatty acid (FFA) in the ICO group were greater than those in the GLU group. Metaregression analysis showed that TC levels positively correlated with its baseline levels. In the subgroup of patients with dialysis duration more than 6 months, TC and TG in the ICO group were less. In pooled data from cross-sectional studies, differential of TG in the ICO group was less. In the subgroup of patients with diabetes (Martikainen et al., 2005, Sniderman et al., 2014, and Takatori et al., 2011), differential of high-density lipoprotein cholesterol (HDL-C) in the ICO group was less. There was no significant effect on low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), or lipoprotein(a). CONCLUSIONS: ICO may be beneficial to lipid metabolism, especially for its biphasic regulation of plasma TC levels.

Mequindox induced cellular DNA damage via generation of reactive oxygen species.

Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox-associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using γ-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS.

The mechanism of enzymatic and non-enzymatic N-oxide reductive metabolism of cyadox in pig liver.

Cyadox is a novel quinoxaline-1,4-dioxide with the potential for development as a substitute for the banned veterinary drugs carbadox and olaquindox. In this paper, using pigs as the test subjects, the metabolic mechanism of cyadox N-oxide reduction in liver is demonstrated. There exist two metabolic mechanisms for the N-oxide reduction of cyadox, the enzymatic and non-enzymatic routes. It is found that cyadox can be enzymatically reduced to 4-cyadox monoxide and 1-cyadox monoxide; this process is catalyzed by aldehyde oxidase and xanthine oxidase in the cytosol and by cytochrome b5 reductase in the microsomes. On the other hand, cyadox is only reduced to 4-cyadox monoxide in the non-enzymatic reduction mediated by heme groups of catalase and cytochrome P450s. We supposed that, owing to the position of the side chain in cyadox, the 1-N-oxide and 4-N-oxide bonds in the quinoxaline ring had different biochemical activities, which caused cyadox to be shunted to the distinct metabolic mechanisms. Additionally, this research gives the first evidence of FAD- and NAD(P)H-dependent non-enzymatic catalase reduction of a heterocyclic N-oxide. The research provides a basic foundation for the formulation of safety controls for animal products and the properties and metabolism of heterocyclic N-oxides.