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A persistent mystery in the melanoma field has been the function of one of the first melanoma tumor antigens characterized, namely p97 (melanotransferrin; MTf). While MTf expression increases melanoma cell proliferation, migration, and tumorigenesis, the molecular mechanism responsible is unknown. On the other hand, N-myc down-stream regulated gene 1 (NDRG1) is a potent metastasis suppressor and WNT antagonist. Expression of NDRG1 in melanoma cells suggests a role in inhibiting metastasis, with this study investigating MTf’s role in oncogenic signaling. We demonstrate MTf acts as a pro-oncogenic WNT agonist, which down-regulates NDRG1, while silencingMTfincreases NDRG1 expression. In contrast, silencingNDRG1increases MTf expression. These observations demonstrate a bidirectional negative feedback loop and “Yin-Yang” relationship between MTf and NDRG1. Mechanistically, MTf was directly associated with the WNT co-receptor, lipoprotein-receptor 6 (LRP6), and increased total LRP6 expression, activated p-LRP6 (Ser1490), β-catenin, and activated β-catenin (Ser552) levels, with MTf expression inducing their nuclear accumulation. Additionally, MTf expression increased downstream WNT targets, namely cyclin D1 and c-Myc, with c-Myc down-regulating NDRG1 expression. Silencingc-Mycprevented the Yin-Yang relationship between NDRG1 and MTf, indicating c-Myc played a key role in their inverse regulation. Melanoma patient specimens demonstrated that a low NDRG1/MTf ratio was significantly (p= 0.008) associated with lower survival and metastasis. Chemotherapeutic agents that up-regulated NDRG1 depressed MTf and nuclear LRP6 and potently inhibited melanoma xenograft growthin vivo. This study demonstrates MTf acts as a WNT agonist, with a Yin-Yang relationship being observed with the WNT antagonist, NDRG1.

Strelitzia reginae is a popular cut flower that has blue petals and orange sepals. Flower color is an important plant trait; however, little is known about its molecular mechanisms in S. reginae. In this study, cDNA libraries were constructed for blue petals and orange sepals of S. reginae. A total of 75 487 unigenes were obtained from transcriptome sequencing and de novo assembly, of which 41.86 % were annotated by public databases. Ultra-high performance liquid chromatography analysis revealed that anthocyanins were the main pigment in blue petals, and that carotenoids controled pigment formation in the orange sepals. Using a system analysis-based approach, 73 and 29 candidate genes related to anthocyanin and carotenoid biosyntheses were identified, respectively. Among these, chalcone synthase 2, chalcone isomerase 1, flavanone 3-hydroxylase 1, flavonoid 3',5'-hydroxylase 1, dihydroflavonol 4-reductase 1, anthocyanidin synthase 1, and anthocyanidin 3-O-glucosyltransferase 1 were considered to be important in regulating the formation of blue petals, and phytoene synthase 1, phytoene desaturaser 1, ζ-carotene desaturase 1, lycopene β-cyclase 3, and β-carotene hydroxylase 2 might play important roles in orange sepal formation. This study improves our understanding of flower color and provides evidence for future molecular breeding of ornamental plants based on flower color modifications.

The preferred orientation full intermetallic compound (IMC) interconnects were fabricated using the current driven bonding (CDB) method. The electromigration behavior and mechanical properties of the (001) Cu/IMC(30 µm Cu6Sn5)/Cu interconnects under a current density of 2.0×10^4 A/cm2 at 150 °C and 180 °C were investigated. The Cu/Cu6Sn5/Cu IMC interconnects exhibited an excellent electromigration resistance, since there was no obvious damage after aging at 150 °C and 180 °C for 200 h, and even after electromigration under 2.0×10^4 A/cm2 at 150 °C and 180 °C for 200 h. The microstructural evolution of the Cu/Cu6Sn5/Cu IMC interconnects undergoing aging and electromigration was mainly the growth of interfacial Cu3Sn and formation of Kirkendall voids in Cu3Sn. Electromigration significantly accelerated the growth of interfacial Cu3Sn IMCs compared with aging, and there was no obvious "polarity effect" for the growth of interfacial Cu3Sn IMCs undergoing electromigration. The Cu/Cu6Sn5/Cu IMC interconnects had a high mechanical reliability even undergoing high temperature aging and high current stressing (electromigration). The average tensile strength of full IMC interconnects remained unchanged, i.e., 82.0 MPa and 81.8 MPa, even after aging at 150 °C for 300 h and electromigration (2.0×10^4 A/cm2) at 150 °C for 300 h, respectively, which were similar to that of the as-soldered state (86.7 MPa). However, the microstructural degradation of traditional Sn-3.0Ag-0.5Cu solder interconnects undergoing electromigration was greatly serious, and the Sn-3.0Ag-0.5Cu solder interconnects failed even after electromigration at 150 oC for less than 100 h. The present work is expected to provide a guidance for the promising application of the preferred orientation full IMC interconnects in 3D integrated circuits packaging.