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Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA‐based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy‐induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF‐1 in response to chemotherapy. Genetic inhibition of HIF‐1‐controlled polyamine anabolism blocks chemotherapy‐induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF‐1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy‐induced HIF‐1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Developing organic aggregation-induced emission luminogens (AIEgens) with a donor–acceptor–donor (D–A–D) structure improves fluorescence imaging for biological applications due to their deep tissue penetration, high fluorescence quantum yield, and good biocompatibility. However, compared to the systematically well-explored near-infrared-I (NIR-I, 650–900 nm) AIEgens, the research on organic D–A–D-type near-infrared-II (NIR-II, 1000–1700 nm) AIEgens received a snub, by contrast, owing to their lack of diversity, low AIE character, and poor tumor accumulation, which has become a bottleneck in the bioimaging field. Herein, we report a D–A–D-type organic NIR-II fluorophore with typical AIE character (αAIE > 4) through careful manipulation of the electron donor and acceptor. The tumor-associated macrophage (TAM)-derived exosomes with nanometer size were used as templates to encapsulate the NIR-II AIEgens (oBBT-DPNA) in a well-defined structure (named as AIE@Exo). The AIE@Exo displayed a superb aggregation-intensified NIR-II fluorescence with a maximum emission peak at 1052 nm as well as a calculated fluorescence quantum yield (QY) of 3.1%. Moreover, the in vivo application of AIE@Exo in efficient NIR-II fluorescence imaging of whole-body vessels and tumor was successfully demonstrated in living mice. Overall, the nanometer-sized biomimetic nanoparticles represent successful NIR-II AIE nanoparticles for biomedical imaging. [ABSTRACT FROM AUTHOR]

Macleaya cordata is a dominant plant of mine tailings and a zinc (Zn) accumulator with high Zn tolerance. In this study, M. cordata seedlings cultured in Hoagland solution were treated with 200 μmol·L−1 of Zn for 1 day or 7 days, and then, their leaves were taken for a comparative analysis of the transcriptomes and proteomes between the leaves of the control and Zn treatments. Differentially expressed genes included those that were iron (Fe)-deficiency-induced, such as vacuolar iron transporter VIT, ABC transporter ABCI17 and ferric reduction oxidase FRO. Those genes were significantly upregulated by Zn and could be responsible for Zn transport in the leaves of M. cordata. Differentially expressed proteins, such as chlorophyll a/b-binding proteins, ATP-dependent protease, and vacuolar-type ATPase located on the tonoplast, were significantly upregulated by Zn and, thus, could be important in chlorophyll biosynthesis and cytoplasm pH stabilization. Moreover, the changes in Zn accumulation, the production of hydrogen peroxide, and the numbers of mesophyll cells in the leaves of M. cordata were consistent with the expression of the genes and proteins. Thus, the proteins involved in the homeostasis of Zn and Fe are hypothesized to be the keys to the tolerance and accumulation of Zn in M. cordata. Such mechanisms in M. cordata can suggest novel approaches to genetically engineering and biofortifying crops. [ABSTRACT FROM AUTHOR]