Demanded as an essential trace element that supports cell growth and basic functions, iron can be harmful and cancerogenic though. By exchanging between its different oxidized forms, iron overload induces free radical formation, lipid peroxidation, DNA, and protein damages, leading to carcinogenesis or ferroptosis. Iron also plays profound roles in modulating tumor microenvironment and metastasis, maintaining genomic stability and controlling epigenetics. in order to meet the high requirement of iron, neoplastic cells have remodeled iron metabolism pathways, including acquisition, storage, and efflux, which makes manipulating iron homeostasis a considerable approach for cancer therapy. Several iron chelators and iron oxide nanoparticles (IONPs) has recently been developed for cancer intervention and presented considerable effects. This review summarizes some latest findings about iron metabolism function and regulation mechanism in cancer and the application of iron chelators and IONPs in cancer diagnosis and therapy.
Tumor associated macrophages (TAMs) play an important role in tumorigenesis, development and anti-cancer drug therapy. However, very few epigenetic compounds have been elucidated to affect tumor growth by educating TAMs in the tumor microenvironment (TME). Herein, we identified that EZH2 performs a crucial role in the regulation of TAMs infiltration and protumoral polarization by interacting with human breast cancer (BC) cells. We showed that EZH2 inhibitors-treated BC cells induced M2 macrophage polarization in vitro and in vivo, while EZH2 knockdown exhibited the opposite effect. Mechanistically, inhibition of EZH2 histone methyltransferase alone by EZH2 inhibitors in breast cancer cells could reduce the enrichment of H3K27me3 on CCL2 gene promoter, elevate CCL2 transcription and secretion, contributing to the induction of M2 macrophage polarization and recruitment in TME, which reveal a potential explanation behind the frustrating results of EZH2 inhibitors against breast cancer. On the contrary, EZH2 depletion led to DNA demethylation and subsequent upregulation of miR-124-3p level, which inhibited its target CCL2 expression in the tumor cells, causing arrest of TAMs M2 polarization. Taken together, these data suggested that EZH2 can exert opposite regulatory effects on TAMs polarization through its enzymatic or non-enzymatic activities. Our results also imply that the effect of antitumor drugs on TAMs may affect its therapeutic efficacy, and the combined application with TAMs modifiers should be warranted to achieve great clinical success.
Network embedding (NE) aims to represent network information appropriately by learning low-dimensional and dense vectors for the nodes and edges of information network. Actually, the real world is almost full of heterogeneous information networks, which stimulates the emergence of heterogeneous information networks (HINs) embedding models. However, parts of existing HIN embedding models like meta-path-based methods only capture limited and aggregated information of relations, whereas some models based on metric or distance learning are usually of high computational complexity and slow training speed. In this paper, we present a novel heterogeneous information network embedding model, which applies dynamic projection metrics and translation mechanisms to the complicated heterogeneous information networks including multiple nodes and different relations. In order to overcome the imbalance of the distribution of relations in HIN and optimize the training process, we introduce an adaptive loss function for model optimization. Further more, we propose a hybrid model with baseline method as the initialization of the model. Experiments have been implemented on some real-world HIN datasets. And empirical results show that our model significantly outperforms the state-of-the-art representation learning models.
INDEX TERMSDynamic projected embedding, heterogeneous information network, network representation learning.
Semiconductor optical amplifiers (SOAs) offer direct electrical injection, power consumption, integration, and anti-radiation advantages over optical fiber amplifiers. However, saturation output power and gain bandwidth have been limited in traditional structure SOAs. We demonstrate a monolithic integrated SOA with broad spectrum, high power, high gain, and small spectral linewidth expansion. The device adopts a two-stage amplified large optical cavity structure, and a lower optical field confinement factor was obtained by adjusting the thickness of the waveguide layer. The lower optical field confinement factor is conducive to improving the coupling efficiency and the maximum output power. Our device, fabricated only by standard i-line lithography with micron-scale precision, obtains excellent and stable performance. When the input power is set to 1 mW, the output power is 419 mW with a gain of 26.23 dB. When the input power is set to 25 mW at 25 °C , the output power increases to 600 mW with a gain of 13.8 dB. The corresponding gain bandwidth of 3 dB measures at least 70 nm. The spectral linewidth after the SOA is 1.15 times wider than that of the seed laser.INDEX TERMS broad spectrum, high gain, high power, semiconductor optical amplifiers, small linewidth expansion.
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