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More than 90% of NPM1-mutated acute myeloid leukaemia (NPM1

Background Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive and poor prognostic malignant tumor along with high-level infection of Epstein-Barr virus (EBV). Gemcitabine (Gem) and Thymosin alpha 1 (Tα1) exert an anti-tumor effect in various cancers. However, the effect of the combination of Gem and Tα1 in NNKTL remains unknown. Methods SNK6 cells were treated with Gem, Tα1 and Gem plus Tα1 for 48 h. The expression levels of EBV and inflammatory factors were measured by qRT-PCR assay. The effect of Gem and Tα1 on cell viability, proliferation, apoptosis, autophagy was detected by CCK-8, colony formation, flow cytometry, autophagic flux measurement, respectively. Western blot was used to evaluate the expression of proteins related to epithelial-mesenchymal transition (EMT), apoptosis and autophagy. In vivo xenograft models were used to further verify the roles of Gem and Tα1. Tumors were removed for weight measurement, H&E and IHC staining. Results We identified that the half maximal inhibitory concentration (IC50) of Gem and Tα1 was 116.5 μmol/ml and 1.334 μmol/ml. Alone or combined administration of Gem and Tα1 dramatically attenuated the EBV viral load and promoted inflammatory factors expression in SNK6 cells, among which the combination of Gem and Tα1 treatment showed the most significant effect. Besides, combination treatment with Gem and Tα1 markedly inhibited cell growth and EMT progress, and enhanced apoptosis and autophagy. Similarly, Gem combined with Tα1 suppressed tumor growth, promoted apoptosis and autophagy in vivo. Additionally, combination treatment with Gem and Tα1 inhibited PI3K/AKT/mTOR pathway. Conclusion In summary, combination administration of Gem and Tα1 suppressed the progression of NNKTL in vivo and in vitro. Our study provided an effective therapeutic strategy potentially for the clinical treatment of NNKTL.

An as-cast Mg–Al–Y–Zn alloy was successfully processed by equal channel angular extrusion (ECAE) in the temperature range of 225–400 °C, and the influences of processing temperature on the microstructure and mechanical properties were investigated. The use of back pressure during one-pass ECAE of Mg–Al–Y–Zn alloy was favorable for eliminating the undeformed area in the billet. At the processing temperature below 250 °C, the microstructures were characterized by unrecrystallised structure and the precipitated phase Mg 17 Al 12 was elongated along the extrusion direction. With increasing processing temperature to 350 °C, a large number of recrystallised grains were obtained. Increasing processing temperature promoted workability but led to decrease in the strength of Mg–Al–Y–Zn alloy. Then billets of as-cast Mg–Al–Y–Zn alloy were extruded at different numbers of ECAE passes. It was found that the microstructure was effectively refined by ECAE and mechanical properties were improved with numbers of ECAE passes increasing from one-pass to four passes. However, strengths decreased slightly after five passes though the grain size decreased considerably.

Semi-solid processing of magnesium alloys is generally based on conventional magnesium-based casting alloys such as Mg–Al series. However, these casting alloys do not give such high mechanical properties as the alloys that are conventionally wrought such as Mg–Zn series. In this paper, a ZK60 magnesium alloy with the addition of Y was thixoforged. The semi-solid thermal transformation (SSTT) route and the recrystallisation and partial melting (RAP) route were used to obtain the semi-solid feedstocks for thixoforging. Microstructural evolution during partial remelting was studied at temperatures for times. Tensile mechanical properties of thixoforged components at room temperature were examined. Results show that a fine spheroidal microstructure can be obtained by the RAP route. Compared to the RAP route, the SSTT alloy shows coarsened solid grains with a relatively high proportion of intragranular liquid droplets. With prolonged holding time, the solid grain sizes of the SSTT alloy and the RAP alloy increased. Coalescence was dominant in the SSTT alloy and Ostwald ripening was dominant in the RAP alloy. Thixoforging for the SSTT alloy and the RAP alloy resulted in successful filling of the die. The tensile properties of the thixoforged RAP alloy were satisfactory and exceeded those of the thixoforged SSTT alloy. However, the mechanical properties of both the thixoforged SSTT alloy and the thixoforged RAP alloy decreased with prolonged holding time.