The Effect of Optimized Substrate Orientation on Layer Step in Laser Metal Deposition of Single-Crystal Nickel-Base Superalloys.

Laser metal deposition is a promising way to repair the surface defects of single-crystal components in turbo engines. Understanding the mechanisms and improving the efficiency of the repair have been long-standing problems. In this study, the influence of the substrate orientation on the laser metal deposition (LMD) was investigated and its effect on repair layer-step was examined. LMD experiments were conducted on single crystal superalloys with a normal substrate orientation (001)/[100] and with an optimized substrate orientation (101)/[101¯]. It reveals that the laser cladding with the optimized orientation leads to a larger height of the [001] dendrite region than that with the normal orientation. The calculated results of the growth velocity, thermal gradient, and susceptibility to CET in the dendrite-preferred growth direction indicate that, for the (101)/[101¯] orientation, the [001]/[100] boundary is located at relative high position in each layer, which not only decreases the formation ability of stray grain significantly, but also eliminates the appearance of the maximum susceptibility. This makes the necessary dilution position much higher, and thus, a large cladding step can be selected. Our findings could find potential applications in laser repair of single-crystal components.

Cadherin-dependent adhesion modulated 3D cell-assembly.

The emergence of synthetic biology has opened new avenues in constructing cell-assembly biosystems with specific gene expression and function. The phenomena of cell spreading and detachment during tissue development and cancer metastasis are caused by surface tension, which in turn results from differences in cell-cell adhesion mediated by the dimerization of cadherin expressed on the cell surface. In this study, E- and P-cadherin plasmids were first constructed based on the differential adhesion hypothesis, then they were electroporated into K562 cells and HEK293T cells, respectively, to explore the process of cell migration and assembly regulated by cadherins. Using this approach, some special 3D cell functional components with a phase separation structure were fabricated successfully. Our work will be of potential application in the construction of self-assembling synthetic tissues and organoids.

Defective arginine metabolism impairs mitochondrial homeostasis in Caenorhabditiselegans.

Arginine catabolism involves enzyme-dependent reactions in both mitochondria and the cytosol, defects in which may lead to hyperargininemia, a devastating developmental disorder. It is largely unknown if defective arginine catabolism has any effects on mitochondria. Here we report that normal arginine catabolism is essential for mitochondrial homeostasis in Caenorhabditiselegans. Mutations of the arginase gene argn-1 lead to abnormal mitochondrial enlargement and reduced adenosine triphosphate (ATP) production in C. elegans hypodermal cells. ARGN-1 localizes to mitochondria and its loss causes arginine accumulation, which disrupts mitochondrial dynamics. Heterologous expression of human ARG1 or ARG2 rescued the mitochondrial defects of argn-1 mutants. Importantly, genetic inactivation of the mitochondrial basic amino acid transporter SLC-25A29 or the mitochondrial glutamate transporter SLC-25A18.1 fully suppressed the mitochondrial defects caused by argn-1 mutations. These findings suggest that mitochondrial damage probably contributes to the pathogenesis of hyperargininemia and provide clues for developing therapeutic treatments for hyperargininemia.

Oxycodone versus morphine for cancer pain titration: A systematic review and pharmacoeconomic evaluation.

OBJECTIVE: To evaluate the efficacy, safety and cost-effectiveness of Oxycodone Hydrochloride Controlled-release Tablets (CR oxycodone) and Morphine Sulfate Sustained-release Tablets (SR morphine) for moderate to severe cancer pain titration. METHODS: Randomized controlled trials meeting the inclusion criteria were searched through Medline, Cochrane Library, Pubmed, EMbase, CNKI,VIP and WanFang database from the data of their establishment to June 2019. The efficacy and safety data were extracted from the included literature. The pain control rate was calculated to eatimate efficacy. Meta-analysis was conducted by Revman5.1.4. A decision tree model was built to simulate cancer pain titration process. The initial dose of CR oxycodone and SR morphine group were 20mg and 30mg respectively. Oral immediate-release morphine was administered to treat break-out pain. The incremental cost-effectiveness ratio was performed with TreeAge Pro 2019. RESULTS: 19 studies (1680 patients)were included in this study. Meta-analysis showed that the pain control rate of CR oxycodone and SR morphine were 86% and 82.98% respectively. The costs of CR oxycodone and SR morphine were $23.27 and $13.31. The incremental cost-effectiveness ratio per unit was approximate $329.76. At the willingness-to-pay threshold of $8836, CR oxycodone was cost-effective, while the corresponding probability of being cost-effective at the willingness-to-pay threshold of $300 was 31.6%. One-way sensitivity analysis confirmed robustness of results. CONCLUSIONS: CR oxycodone could be a cost-effective option compared with SR morphine for moderate to severe cancer pain titration in China, according to the threshold defined by the WHO.