Fault-tolerant four-dimensional constellation for coherent optical transmission systems.

We propose a 4-dimensional 2-ary amplitude ring-switched modulation format with 64 symbols, which is denoted as 4D-2A-RS64 encoded over two polarization tributaries to improve the transmission performance over long-haul optical fibers in the presence of the non-linear Kerr effect. At a spectral efficiency of 6 bits per 4D, simulation results show that this format outperforms the polarization division multiplexed (PDM) 8QAM-star modulation as well as the 4D-2A-8PSK over links without inline dispersion management. We evaluate the performance for a WDM transmission of 11 × 90~Gbaud channels over a multi-span SSMF link. For an achievable information rate of 4.8bit/s/Hz, the maximum transmission distance is improved by 10.6% (400 km) and 4% (160 km) compared to PDM-8QAM-star and 4D-2A-8PSK respectively. The achieved gains are composed of a linear part and a non-linear part, respectively from the improved Euclidean-distance distribution and the constant power property of the 4D modulation. The geometric shaping of the proposed scheme is easy to implement and is robust to Mach-Zehnder modulator (MZM) imbalances and quantization errors stemming from the finite digital-to-analog converter (DAC) resolution. This robustness is compared to the one of other geometric-shaped non-linearity tolerant 4D schemes such as the 4D-2A-8PSK and the 4D-64PRS that can be both outperformed by our scheme in severe conditions.

Endoscopic retrograde appendicitis therapy versus laparoscopic appendectomy versus open appendectomy for acute appendicitis: a pilot study.

BACKGROUND: An increasing number of studies have shown the merits of endoscopic retrograde appendicitis therapy (ERAT) in diagnosing and treating acute uncomplicated appendicitis. However, no related prospective controlled studies have been reported yet. Our aim is to assess the feasibility and safety of ERAT in the treatment of acute uncomplicated appendicitis. METHODS: In this open-label, randomized trial, participants were randomly allocated to the ERAT group, laparoscopic appendectomy (LA) group and open appendectomy (OA) group. The primary outcome was the clinical success rate of the treatment. Intention-to-treat analysis was used in the study. RESULTS: The study comprised of 99 patients, with 33 participants in each group. The clinical success rate was 87.88% (29/33), 96.97% (32/33) and 100% (33/33) in the ERAT, LA and OA group, respectively. In the ERAT group, 4 patients failed ERAT due to difficult cannulation. In LA group, 1 patient failed because of abdominal adhesion. There were no significant differences among the three treatment groups regarding the clinical success rate (P = 0.123). The median duration of follow-up was 22 months. There were no significant differences (P = 0.693) among the three groups in terms of adverse events and the final crossover rate of ERAT to surgery was 21.21% (7/33). CONCLUSION: ERAT can serve as an alternative and efficient method to treat acute uncomplicated appendicitis. Trial registration The study is registered with the WHO Primary Registry-Chinese Clinical Trial Registry (ChiCTR1900025812).

Butein Inhibited In Vitro Hexokinase-2-Mediated Tumor Glycolysis in Hepatocellular Carcinoma by Blocking Epidermal Growth Factor Receptor (EGFR).

BACKGROUND Anaerobic glycolysis is an important physiological process of all cancer cells. Butein has been reported to demonstrate substantial antitumor activities in various cancers. However, the effect of butein on tumor glycolysis remains unclear. In this study, the effect of butein on tumor glycolysis and the underlying mechanism were investigated in hepatocellular carcinoma (HCC). MATERIAL AND METHODS Cell proliferation assay and anchorage-independent growth assay were carried out to evaluate the antitumor activities of butein in vitro. The effect of butein on tumor glycolysis was determined by examining the changes in glucose uptake and lactate production. Hexokinase-2 (HK-2) expression in HCC cells upon butein treatment was analyzed by Western blotting. The activity of butein on EGFR signaling pathway was studied and its potency in EGFR exogenous overexpression cells was investigated. RESULTS After butein treatment, HCC cell proliferation was significantly inhibited (91.4% in Hep3B and 88.2% in Huh-7 at 80 µM, p<0.001). Moreover, the number of colonies formed in the agar was substantially decreased (93.8% in Hep3B and 72.3% in Huh-7 at 80 µM, p<0.001). With the suppression of HK-2 expression, glucose consumption in Hep3B and Huh-7 cells decreased by 48.4% and 56.3%, respectively (p<0.01), and the lactate production also was reduced accordingly (39.5% in Hep3B and 48.6% in Huh-7, p<0.01). Mechanism investigations demonstrated that butein dose-dependently blocked the activation of the EGFR signaling pathway in HCC cells. In EGFR exogenous overexpression cells, the glycolysis suppression exerted by butein was substantially attenuated. CONCLUSIONS Butein has a substantial inhibitory effect on tumor glycolysis in HCC cells, and the glycolysis suppression exerted by butein is closely related to its effect on the EGFR signaling pathway.

3-(3,4-Dihydroxyphenyl)-1-methoxy-1-oxopropan-2-aminium chloride.

In the title compound, C(10)H(14)NO(4) (+)·Cl(-), the benzene ring makes a dihedral angle of 64.68 (4)° with the methyl-amino-propano-ate unit, which is bonded to the catechol ring via a methyl-ene C atom. A strong intra-molecular O-H⋯O hydrogen bond occurs. In the crystal, O-H⋯O, N-H⋯Cl and O-H⋯Cl hydrogen bonds and weak C-H⋯O inter-actions link the mol-ecules into a three-dimensional network.

By blocking hexokinase-2 phosphorylation, limonin suppresses tumor glycolysis and induces cell apoptosis in hepatocellular carcinoma.

INTRODUCTION: The purpose of present study was to investigate the effect of limonin on tumor glycolysis and the underlying mechanisms in hepatocellular carcinoma (HCC). METHODS: Cell proliferation and colony formation assays were performed to evaluate the potency of limonin against HCC cells in vitro. The glucose consumption and lactate production after limonin treatment was determined. The effect of limonin on hexokinase-2 (HK-2) activity was assessed and the mitochondrial location of HK-2 was studied by immunoprecipitation. Cell apoptosis and protein expression were detected by flow cytometry and western blotting respectively. Protein overexpression by plasmid transfection was adopted to investigate the molecular mechanisms. RESULTS: HCC proliferation and colony formation were inhibited by limonin in vitro. With the suppression of HK-2 activity, the glycolytic level in HCC cells was substantially reduced, which was evidenced by the decrease of glucose consumption and lactate production. The phosphorylation of HK-2 was substantially inhibited by limonin, which resulted in the disassociation of HK-2 from mitochondria. Due to the reduction of HK-2 in mitochondria, increasing Bax were shifted to the mitochondria and gave rise to the release of cytochrome C, which induced HCC cells to subject to mitochondria-mediated apoptosis. Mechanism investigations revealed that the decrease of HK-2 phosphorylation was mainly due to the inhibition of Akt activity. In Akt exogenously overexpressed HCC cells, limonin-mediated cell proliferation inhibition, glycolysis suppression and apoptosis induction were significantly impaired. CONCLUSION: Limonin inhibited the tumor glycolysis in hepatocellular carcinoma by suppressing HK-2 activity, and the suppression of HK-2 was closely related to the decrease of Akt activity.

MicroRNA-155 acts as a tumor suppressor in colorectal cancer by targeting CTHRC1 in vitro.

Colorectal cancer is one of the most common malignancies. Aberrant expressed microRNAs (miRNAs) have been demonstrated to have strong associations with colorectal cancer by repressing their targets. Therefore, miRNAs are thought to have significant promise in the diagnosis and prognosis of colorectal cancer. Previous studies indicated that miR-155 and collagen triple helix repeat containing 1 (CTHRC1) were both involved in pathogenesis of colorectal cancer, but the underlying mechanisms of miR-155 and CTHRC1 are still unknown. The present study aimed to investigate the biological functions of miR-155 and CTHRC1 in colorectal cancer. Reverse transcription-quantitative polymerase chain reaction was used to examine miR-155 and CTHRC1 expression levels. A dual-luciferase reporter assay was applied to verify the target interaction between miR-155 and CTHRC1. Proliferation, cell cycle, apoptosis, cell migration and invasion were measured using the MTT assay, flow cytometry and Transwell assays, respectively. Results showed that miR-155 expression was decreased, but CTHRC1 expression was increased in colorectal cancer tissue and cell lines. Furthermore, it was demonstrated that miR-155 negatively regulated CTHRC1. Additionally, miR-155 overexpression suppressed cell proliferation, induced cell cycle arrest and promoted cell apoptosis, while an inhibitor of miR-155 facilitated cell proliferation and cell cycle and repressed apoptosis. Transwell experiments indicated that miR-155 inhibited the cell migratory and invasive abilities of HT-29 cells, but miR-155 inhibitor enhanced these abilities of HT-29 cells. These results suggested that miR-155 prevented colorectal cancer progression and metastasis via silencing CTHRC1 in vitro, which provides evidence for miR-155 and CTHRC1 as a novel anti-onco molecular target for the treatment of colorectal cancer in the future.

Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo.

Breast cancer remains a major cause of cancer-related death in women worldwide. Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of breast cancer. Moreover, it was found that GIT1 was widely involved in the development of many human cancers. Herein, we aimed to investigate the expression changes of miR-149* and GIT1 and the functional effects of miR-149*/GIT1 link in breast cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot (WB) were used to examine the expression levels of miR-149* and GIT1. Dual luciferase reporter assay was utilized to confirm the target interaction between miR-149* and GIT1. The biological functions, including cell proliferation, invasion, and migration, of miR-149* and GIT1 were determined by MTT assay and Transwell assays, respectively. Eventually, the tumor xenograft model in nude mice injected with stable transfected MDA-MB-231 cells was established to verify the effects of miR-149* and GIT1 on tumor growth. Our results showed that miR-149* expression was decreased, whereas GIT1 expression was increased in clinical samples of breast cancer. Based on the inverse expression trend between miR-149* and GIT1, we further demonstrated that miR-149* indeed directly targets GIT1. Subsequently, it was observed that inhibition of miR-149* significantly promoted cell proliferation, invasion, and migration, but the ability of cell proliferation, invasion, and migration was obviously declined after silencing of GIT1 in MDA-MB-231 cells transfected with miR-149* mimic and/or si-GIT1. Finally, it was also found that elevated miR-149* decelerated the tumor growth, while restored GIT1 accelerated the tumor growth in nude mice after 35 days of tumor xenograft. Collectively, these findings concluded that miR-149* might exert a tumor suppressive role in breast cancer by targeting GIT1.