JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1

Despite significant improvements in five-year survival rates due to early diagnosis and combination therapy, triple-negative breast cancer (TNBC) treatment remains a major challenge. Finding new and effective targets for diagnosis and drug therapy is urgent for TNBC patients. Jagged-1 (JAG1), one of the canonical ligands of the Notch signaling pathway, is involved in vascular budding and is a poor prognostic factor of TNBC. In this study, combined with quantitative real-time PCR, database analysis, animal experiments, and other means, JAG1 was confirmed to be related to the poor prognosis of TNBC patients. JAG1 was highly expressed in MDA-MB-231 Bone (231B) cells, with stronger invasion and metastasis ability than MDA-MB-231 (231) cells. Treatment of human vascular endothelial cells (HUVEC) with TNBC conditioned medium showed that TNBC JAG1 promoted the angiogenesis of HUVEC. Next, we detected the exosomes extracted from TNBC conditioned medium and found that JAG1 promoted the exosome secretion from 231 cells via ALIX-RAB11A/RAB35. In addition, we also found that the exosomes from JAG1 overexpressed TNBC cells contained more long non-coding RNA (lncRNA) MALAT1 , and MALAT1 promoted angiogenesis of HUVEC by targeting miR-140-5p . Finally, the angiogenesis-promoting effect of JAG1 in TNBC was further investigated by matrix gel assay. In conclusion, we reveal that JAG1 has a pro-invasion effect on TNBC and is involved in microenvironment angiogenesis by promoting exosome secretion and the MALAT1-miR-140-5p-JAG1/VEGFA pathway.

Phase Evolution and Glass Formation in an Fe-Based Alloy

The understanding of phase competing is of pretty importance in designing high glass-forming systems. In this work, it has been investigated experimentally and theoretically the phase evolution and glass formation of a wedge-casting Fe-based alloy. The results indicated that the phase formation was sensitive to the wedge position, i.e., there were amorphous phase, Fe_(2)P, {Fe, Ni} and α-Fe precipitates as well as M_(23)B_(6) phase at the distances of 3, 10 and 20 mm away from the wedge-tip, respectively. These were closely connected with the variation of cooling rate, embodied in the heat transfer at the solidification process. Furthermore, we constructed the time–temperature-transformation (TTT) diagrams of the iron-based alloy and these crystal phases through calculating Rc-related functions. Finally, the glass-forming features of the wedge-shaped Fe-based alloy have been elucidated in accordance with a crystallization kinetics analysis of the recorded temperature data and the phase selection competition. This research provides us an insight into in-depth understanding bulk metallic glass from the perspective of kinetics competition of crystallization phases.

Impact of gas pressure on particle feature in Fe-based amorphous alloy powders via gas atomization:Simulation and experiment

Gas atomization is now an important production technique for Fe-based amorphous alloy powders used in additive manufacturing,particularly selective laser melting,fabricating large-sized Fe-based bulk metallic glasses.Using the realizable k-εmodel and discrete phase model theory,the flow dynamics of the gas phase and gas-melt two-phase flow felds in the close-wake condition were investigated to establish the correlation between high gas pressure and powder particle characteristics.The locations of the recirculation zones and the shapes of Mach disks were analyzed in detail for the type of discrete-jet closed-coupled gas atomization nozzle.In the gas-phase flow feld,the vortexes,closed to the Mach disk,are found to be a new deceleration method.In the two-phase flow feld,the shape of Mach disk changes from“S”-shape to“Z”-shape under the impact of the droplet flow.As predicted by the wave model,with the elevation of gas pressure,the size of the particle is found to gradually decrease and its distribution becomes more concentrated.Simulation results were compliant with the Fe-based amorphous alloy powder preparation tests.This study deepens the understanding of the gas pressure impacting particle features via gas atomization,and contributes to technological applications.

Effect of Sr on Grain Refinement of Mg–3%Al Alloy Containing Trace Fe by Carbon-Inoculation

Magnesium（Mg）-3% aluminum（Al）（in weight） alloy was modified by carbon（C） inoculation combining with strontium（Sr）.The effects of trace 0.1% iron（Fe） addition and operating sequence of carboninoculation and Fe addition on the grain size of Mg-3%Al alloy were studied.The results reveal that the Sr addition could effectively suppress grain-coarsening resulted from the inclusion of Fe in the carboninoculated Mg-Al alloy.Sr addition could contribute to the formation of the duplex-phase particles that Al-C-rich phases coated on Al-Fe or Al-C-Fe-rich phases,regardless of the Fe addition sequence.These duplex-phase particles should be the potent substrates for α-Mg grains.Consequently,Sr addition could effectively subsidize the inhibiting effect of Fe on grain refinement and the active nuclei were maintained.In other words,Sr plays a counter role in the poisoning effect of Fe on the microstructure of Mg-3%Al alloy.