Up-regulation of CNDP2 facilitates the proliferation of colon cancer

BACKGROUND: Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. METHODS: We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. RESULTS: The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. CONCLUSIONS: Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo

Reduction of gas bubbles and improved critical current density in Bi-2212 round wire by swaging

Bi-2212 round wire is made by the powder-in-tube technique. An unavoidable property of powder-in-tube conductors is that there is about 30% void space in the as-drawn wire. We have recently shown that the gas present in the as-drawn Bi-2212 wire agglomerates into large bubbles and that they are presently the most deleterious current limiting mechanism. By densifying short 2212 wires before reaction through cold isostatic pressing (CIPping), the void space was almost removed and the gas bubble density was reduced significantly, resulting in a doubled engineering critical current density (JE) of 810 A/mm2 at 5 T, 4.2 K. Here we report on densifying Bi-2212 wire by swaging, which increased JE (4.2 K, 5 T) from 486 A/mm2 for as-drawn wire to 808 A/mm2 for swaged wire. This result further confirms that enhancing the filament packing density is of great importance for making major JE improvement in this round-wire magnet conductor.Comment: To be published in IEEE Transactions on Applied Superconductivity, 23, xxxxxx (2013

Peripheral Blood Lymphocyte Subsets Predict the Efficacy of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer

BackgroundNon–small cell lung cancer (NSCLC) has entered the era of immunotherapy. However, only partial patients were able to benefit from immune checkpoint inhibitors (ICIs). Currently, biomarkers for predicting patients’ response to ICIs are primarily tumor tissue dependent and have limited accuracy. There is an urgent need to explore peripheral blood-based biomarkers to predict the efficacy and safety of ICI therapy.MethodsTo explore the correlation between lymphocyte subsets and the efficacy and safety of ICIs, we retrospectively analyzed peripheral blood lymphocyte subsets and survival prognosis data of 136 patients with stage IV NSCLC treated with ICIs.ResultsThe two factors that had the greatest impact on the prognosis of patients with NSCLC treated with ICIs were CD4+CD45RA− T cell (HR = 0.644, P = 0.047) and CD8+ T/lymphocyte (%) (HR = 1.806, P = 0.015). CD4+CD45RA− T cell showed excellent predictive efficacy (AUC = 0.854) for ICIs monotherapy, with a sensitivity of 75.0% and specificity of 91.7% using CD4+CD45RA− T cell >311.3 × 106/L as the threshold. In contrast, CD8+ T/lymphocyte (%) was only associated with the prognosis but had no predictive role for ICI efficacy. CD4+ T cell and its subsets were significantly higher in patients with mild (grades 1–2) immune-related adverse events (irAEs) than those without irAEs. CD8+CD38+ T cell was associated with total irAEs and severe (grades 3–4) irAEs but was not suitable to be a predictive biomarker.ConclusionPeripheral blood CD4+CD45RA− T cell was associated with the prognosis of patients with NSCLC applying ICIs, whereas CD8+CD38+ T cell was associated with irAEs and severe irAEs

MicroRNA-127 Post-Transcriptionally Downregulates Sept7 and Suppresses Cell Growth in Hepatocellular Carcinoma Cells

Background/Aims: Hepatocellular carcinoma is one of the most common cancers worldwide. It has been suggested that microRNAs, a class of small regulatory RNAs, are associated with tumorigenesis by targeting the mRNAs of hundreds of genes that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism, and proliferation. Methods/Results: we analyzed the expression levels of mir-127 in 33 HCC and non-cancerous tissues using qRT-PCR. MiR-127 is downregulated in 69.7% of HCC tissues compared with adjacent normal tissues, but its expression level is not correlated with the TNM stage, AFP level, or age. In vitro, miR-127 can arrest Huh7 at the G2/M phase and inhibit Huh7 cell proliferation. In an in vivo xenograft model, the overexpression of miR-127 can inhibit Huh7 cell tumorigenicity. The luciferase reporter and western blot results confirm that miR-127 downregulates Sept7 expression by targeting its 3'UTR. Furthermore, the knockdown of Sept7 has the same effect on cell proliferation as the overexpression of miR-127 in Huh7 cells. Conclusion: miR-127 plays a tumor-suppressor role and can serve as a potential diagnostic biomarker for HCC

Influences of different ECAE routes on filament deformation in Cu clad Nb composite wires

A strategy to obtain higher critical current density (Jc) in Nb 3Sn conductors is to increase the Nb fraction. This can be achieved by improving the deformation behavior of the Nb filaments so less Cu is needed between filaments enabling smaller diameter filaments and more filaments in the subelement region. The objective of this project is to better understand the influence of different pre-processing strain path (texture) on the deformation of a Nb filament in a Cu-matrix. Initial severe plastic deformation by equal channel angular extrusion (ECAE) was used to obtain a uniform fine grain size with slightly different textures in starting Nb rods. Cu-Nb composite bars were warm extruded and wire drawn to evaluate the performance of different starting Nb fine grained microstructures on Nb filament deformation behavior. The initial textures in the various Nb samples were different but quite weak; little difference is seen in the final Nb filament circularities. However, this study indicates the Cu-Nb interface roughness is influenced somewhat by non-uniformity in the Nb microstructure. The evidence suggests that to obtain better deformation characteristics in Nb filaments, one should start with fine-grain weak or untextured Nb with a globally uniform microstructure. This should enable finer as-drawn Nb filaments with better concentricity, composite wires with a higher Nb loading fraction, and conductors with higher Jc. © 2011 IEEE

Heat Treatment Optimization of Rutherford Cables for a 15-T Nb3Sn Dipole Demonstrator

Fermi National Accelerator Laboratory has been developing a 15-T Nb$_3$Sn dipole demonstrator for a future very high energy pp collider based on an optimized 60-mm aperture four-layer “cos-theta” coil. To increase the magnet efficiency, the coil was graded by using two cables with same 15 mm width and different thicknesses made of two different restacked rod process (RRP) wires. Due to the nonuniform field distribution in dipole coils, the maximum field in the inner coil will reach 15-16 T, whereas the maximum field in the outer coil is 12-13 T. In preparation for the 15-T dipole coil reaction, heat treatment studies were performed on strands extracted from these cables with the goal of achieving the best coil performance in the corresponding magnetic fields. In particular, the effect of maximum temperature and time on the cable critical current was studied to take into account actual variations of these parameters during coil reaction. In parallel and in collaboration with Oxford Instruments-Superconducting Technology, development was performed on optimizing Nb$_3$Sn RRP wire design and layout

Heat Treatment Optimization of Rutherford Cables for a 15-T Nb3_3Sn Dipole Demonstrator

Fermi National Accelerator Laboratory has been developing a 15-T Nb$_3$Sn dipole demonstrator for a future very high energy pp collider based on an optimized 60-mm aperture four-layer “cos-theta” coil. To increase the magnet efficiency, the coil was graded by using two cables with same 15 mm width and different thicknesses made of two different restacked rod process (RRP) wires. Due to the nonuniform field distribution in dipole coils, the maximum field in the inner coil will reach 15-16 T, whereas the maximum field in the outer coil is 12-13 T. In preparation for the 15-T dipole coil reaction, heat treatment studies were performed on strands extracted from these cables with the goal of achieving the best coil performance in the corresponding magnetic fields. In particular, the effect of maximum temperature and time on the cable critical current was studied to take into account actual variations of these parameters during coil reaction. In parallel and in collaboration with Oxford Instruments-Superconducting Technology, development was performed on optimizing Nb$_3$Sn RRP wire design and layout

Melatonin Improves the Photosynthetic Carbon Assimilation and Antioxidant Capacity in Wheat Exposed to Nano-ZnO Stress

The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed plants. It was found that melatonin improved the photosynthetic C assimilation in nano-ZnO stressed wheat plants, mainly due to the enhanced photosynthetic energy transport efficiency, higher chlorophyll concentration and higher activities of Rubisco and ATPases. In addition, melatonin enhanced the activities of antioxidant enzymes to protect the photosynthetic electron transport system in wheat leaves against the oxidative burst caused by nano-ZnO stress. These results suggest that melatonin could improve the tolerance of wheat plants to nano-ZnO stress