Nasopharyngeal carcinoma (NPC) has the highest metastasis rate among head and neck cancers with unclear mechanism. WNT5A belongs to the WNT family of cysteine-rich secreted glycoproteins. Our previous high-throughput gene expression profiling revealed that WNT5A was up-regulated in highly metastatic cells. In the present study, we first confirmed the elevated expression of WNT5A in metastatic NPC tissues at both the mRNA and protein levels. We then found that WNT5A promoted epithelial-mesenchymal transition (EMT) in NPC cells, induced the accumulation of CD24-CD44+ cells and side population, which are believed to be cancer stem cell characteristics. Moreover, WNT5A promoted the migration and invasion of NPC cells in vitro, while in vivo treatment with recombinant WNT5A promoted lung metastasis. Knocking down WNT5A diminished NPC tumorigenesis in vivo. When elevated expression of WNT5A coincided with the elevated expression of vimentin in the primary NPC, the patients had a poorer prognosis. Among major signaling pathways, protein kinase C (PKC) signaling was activated by WNT5A in NPC cells. A positive feedback loop between WNT5A and phospho-PKC to promote EMT was also revealed. Taken together, these data suggest that WNT5A is an important molecule in promoting stem cell characteristics in NPC, leading to tumorigenesis and metastasis.

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Abstract. Small interfering RNAs (siRNAs) are valuable reagents for efficient gene silencing in a sequence-specific manner via the RNA interference (RNAi) pathway. The current synthetic siRNA structure consists of symmetrical duplexes of 19-21 base pairs (bp) with 2 nucleotide (nt) 3' overhangs. In this study, we report that an asymmetric siRNA (asiRNA) consisting of 17 bp duplex region (17 bp asiRNA) exhibited potent activity in inhibiting bcl-2 gene expression and cancer cell proliferation in vitro. Importantly, this asiRNA structure significantly reduced off-target silencing by the sense strand. To improve the stability of the 17 bp asiRNA, we synthesized a series of chemically modified 17 bp asiRNAs. Further experiments showed that in comparison with the 17 bp asiRNA, the 17 bp asiRNA-M2, one of the modified 17 bp asiRNAs, exhibited a comparable gene silencing activity and an improved stability in vitro. Furthermore, the 17 bp asiRNA-M2 with a proteolipid micelle delivery system can effectively suppress the growth of H22 and BGC 803 tumors in vivo. These results suggest that the chemically modified asiRNAs may have potential as an effective therapeutic approach for cancer gene therapy in the future.

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Grain boundary engineering (GBE) was employed to control the precipitation behaviour of Hastelloy-X alloy. The precipitate characteristics and thermal stability of grain boundary character distribution (GBCD) were investigated by aging at 850°C. M6C carbides and µ phases were observed in the matrix and on grain boundaries, respectively. It revealed that the formation of µ phase was closely related to the grain boundary structure. GBCD effectively suppressed the nucleation and coarsening of µ phases on the grain boundaries. Owing to the Mo depletion in the vicinity of random grain boundary, the formation of the precipitates was inhibited on the adjacent grain boundaries. The thermal stability of the GBE-optimised microstructure was confirmed at 850°C for 720 h without significant microstructural degradation.

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The flyweight of powder metallurgy is a complex structure part of VE distribution pump. The components of the powder forming process often contain the defects such as instability of the quality, over tolerance of the size accuracy, and disqualification of the appearance. By analyzing the causes of defects and corresponding measures is taken. A once pressing compaction method is used to produce qualified products.