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Cancer‐associated fibroblasts (CAFs) as a predominant cell component in the tumour microenvironment (TME) play an essential role in tumour progression. Our earlier studies revealed oxidized ATM activation in breast CAFs, which is independent of DNA double‐strand breaks (DSBs). Oxidized ATM has been found to serve as a redox sensor to maintain cellular redox homeostasis. However, whether and how oxidized ATM in breast CAFs regulates breast cancer progression remains poorly understood. In this study, we found that oxidized ATM phosphorylates BNIP3 to induce autophagosome accumulation and exosome release from hypoxic breast CAFs. Inhibition of oxidized ATM kinase by KU60019 (a small‐molecule inhibitor of activated ATM) or shRNA‐mediated knockdown of endogenous ATM or BNIP3 blocks autophagy and exosome release from hypoxic CAFs. We also show that oxidized ATM phosphorylates ATP6V1G1, a core proton pump in maintaining lysosomal acidification, leading to lysosomal dysfunction and autophagosome fusion with multi‐vesicular bodies (MVB) but not lysosomes to facilitate exosome release. Furthermore, autophagy‐associated GPR64 is enriched in hypoxic CAFs‐derived exosomes, which stimulates the non‐canonical NF‐κB signalling to upregulate MMP9 and IL‐8 in recipient breast cancer cells, enabling cancer cells to acquire enhanced invasive abilities. Collectively, these results provide novel insights into the role of stromal CAFs in promoting tumour progression and reveal a new function of oxidized ATM in regulating autophagy and exosome release. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) are considered the roots of cancer metastasis and recurrence (CSCs), due in part to their self‐renewal and therapy resistance properties. However, the underlying mechanisms for the regulation of CSC stemness are poorly understood. Recently, increasing evidence shows that long non‐coding RNAs (lncRNAs) are critical regulators for cancer cell function in various malignancies including breast cancer, but how lncRNAs regulate the function of breast cancer stem cells (BCSCs) remains to be determined. Herein, using lncRNA/mRNA microarray assays, a novel lncRNA (named lnc030) is identified, which is highly expressed in BCSCs in vitro and in vivo, as a pivotal regulator in maintaining BCSC stemness and promoting tumorigenesis. Mechanistically, lnc030 cooperates with poly(rC) binding protein 2(PCBP2) to stabilize squalene epoxidase (SQLE) mRNA, resulting in an increase of cholesterol synthesis. The increased cholesterol in turn actives PI3K/Akt signaling, which governs BCSC stemness. In summary, these findings demonstrate that a new, lnc030‐based mechanism for regulating cholesterol synthesis and stemness properties of BCSCs. The lnc030‐SQLE‐cholesterol synthesis pathway may serve as an effective therapeutic target for BCSC elimination and breast cancer treatment. [ABSTRACT FROM AUTHOR]

An in situ TiC–TiB2/Al composite inoculant is prepared by melt spinning the sintered mixture of Al powder, Ti powder, B4C particles, and graphene nanoplates (GNPs). To increase the degree of dispersion of the particles, the GNPs are coated on the surface of the B4C particles by high‐energy ball milling before sintering. The as‐spun inoculant ribbons are added to the melt of a typical Al–Si alloy to verify its effect of refining the grains on aluminum alloys. It is found that the columnar grains of the as‐cast Al–Si alloy sample are refined to finely approximate equiaxed grains, with an addition level of 0.6 wt% of the inoculant ribbons. The mechanical properties of the as‐inoculated Al–Si alloys also improve significantly, and show a remarkable strengthening and toughening effect. It can be attributed to the grain refinement and the dispersion strengthening by the introduction of TiC and TiB2 particles in the Al matrix. The results show that the newly developed composite inoculant ribbons using GNPs can significantly meliorate the overall mechanical performance of typical Al–Si alloys. [ABSTRACT FROM AUTHOR]

The Al–B–Ca alloy ingot is prepared by arc‐melting with Al–3B and Al–10Ca master alloys and the in situ CaB6–Al4Ca/Al composite inoculant ribbon is carried out through melt‐spinning of Al–B–Ca alloy ingot. Afterwards, Al–B–Ca alloy ingot and CaB6–Al4Ca/Al inoculant ribbon are added into the melt of Al–10Si–0.3Mg alloy as inoculants to verify their refining and modifying effects, respectively. It is found whether in Al–B–Ca alloy ingot or CaB6–Al4Ca/Al inoculant ribbon, CaB6 particles have a cubic shape. Compared to the micron‐sized CaB6 particles in the ingot, the size of CaB6 particles in the ribbon can reach to subnanoscale and nanoscale level. With the same amount of addition, CaB6–Al4Ca/Al inoculant ribbon has a better refining effect than Al–B–Ca alloy ingot, but both of them have similar modifying effects for eutectic silicon. In addition, the mechanical properties of Al–10Si–0.3Mg alloy inoculated by the ribbon are superior to that of Al–10Si–0.3Mg alloy inoculated by the ingot. The mismatch between CaB6 and Al is particularly small and certain orientation relationships are existed between them. Therefore, the impact of CaB6 particle size on refining effect of the inoculants, the heterogeneous nucleation mechanism of CaB6, and the strengthening mechanism of Al–10Si–0.3Mg alloy after inoculation are investigated. The in situ CaB6–Al4Ca/Al inoculant ribbon is prepared through melt‐spinning of Al–B–Ca alloy ingot. CaB6–Al4Ca/Al inoculant ribbon has a better refining effect than Al–B–Ca alloy ingot and the mechanical properties of Al–10Si–0.3Mg alloy inoculated by the ribbon are superior to that of Al–10Si–0.3Mg alloy inoculated by the ingot. Crystallographic orientation relationships are existed between CaB6 and Al. [ABSTRACT FROM AUTHOR]