Molecular targeting of cancer stem cells has therapeutic potential for efficient treatment of cancer although relatively few specific targets have so far been identified. Hypoxia-inducible factor was recently shown to regulate tumorigenic capacity of glioma stem cells under hypoxic condition. Surprisingly, we found that, under normoxia, HIF1α signaling was selectively activated in the stem cells of mouse lymphoma and human acute myeloid leukemia (AML). HIF1a ShRNA and HIF inhibitors abrogated the colony forming unit activity of mouse lymphoma and human AML CSCs. Importantly, the HIF inhibitor echinomycin efficiently eradicated mouse lymphoma and serially transplantable human AML in xenogeneic model by preferential elimination of CSCs. HIF1α maintains mouse lymphoma CSCs by repressing a negative feedback loop in the Notch pathway. Taken together, our results demonstrate an essential function of HIF1α-Notch interaction in maintaining CSCs and provide an effective approach to target CSCs for therapy of hematological malignancies.

It is still a grand challenge to develop a highly efficient nonprecious-metal electrocatalyst to replace the Pt-based catalysts for oxygen reduction reaction (ORR). Here, we propose a surfactant-assisted method to synthesize single-atom iron catalysts (SA-Fe/NG). The half-wave potential of SA-Fe/NG is only 30 mV less than 20% Pt/C in acidic medium, while it is 30 mV superior to 20% Pt/C in alkaline medium. Moreover, SA-Fe/NG shows extremely high stability with only 12 mV and 15 mV negative shifts after 5,000 cycles in acidic and alkaline media, respectively. Impressively, the SA-Fe/NG-based acidic proton exchange membrane fuel cell (PEMFC) exhibits a high power density of 823 mW cm Combining experimental results and density-functional theory (DFT) calculations, we further reveal that the origin of high-ORR activity of SA-Fe/NG is from the Fe-pyrrolic-N species, because such molecular incorporation is the key, leading to the active site increase in an order of magnitude which successfully clarifies the bottleneck puzzle of why a small amount of iron in the SA-Fe catalysts can exhibit extremely superior ORR activity.

Currently, developing nonprecious‐metal catalysts to replace Pt‐based electrocatalysts in fuel cells has become a hot topic because the oxygen reduction reaction (ORR) in fuel cells often requires platinum, a precious metal, as a catalyst, which is one of the major hurdles for commercialization of the fuel cells. Recently, the newly emerging metal‐organic frameworks (MOFs) have been widely used as self‐sacrificed precursors/templates to fabricate heteroatom‐doped porous carbons. Here, the recent progress of MOF‐derived, heteroatom‐doped porous carbon catalysts for ORR in fuel cells is systematically reviewed, and the synthesis strategies for using different MOF precursors to prepare heteroatom‐doped porous carbon catalysts, including the direct carbonization of MOFs, MOF and heteroatom source mixture carbonization, and MOF‐based composite carbonization are summarized. The emphasis is placed on the precursor design of MOF‐derived metal‐free catalysts and transition‐metal‐doped carbon catalysts because the MOF precursors often determine the microstructures of the derived porous carbon catalysts. The discussion provides a useful strategy for in situ synthesis of heteroatom‐doped carbon ORR electrocatalysts by rationally designing MOF precursors. Due to the versatility of MOF structures, MOF‐derived porous carbons not only provide chances to develop highly efficient ORR electrocatalysts, but also broaden the family of nanoporous carbons for applications in supercapacitors and batteries.

Using electrochemical water splitting to produce hydrogen is still a grand challenge due to the lack of economical and efficient Pt‐free catalysts. Herein, a single‐atom Ru supported on MoS2 (SA‐Ru‐MoS2) electrocatalyst for the hydrogen evolution reaction (HER) is reported. Results indicate that single‐atom Ru doping induces phase transition of MoS2 and generation of S vacancies, which significantly improve the performance of inert 2D MoS2 for HER. In particular, the SA‐Ru‐MoS2 electrocatalyst exhibits a low overpotential of 76 mV at 10 mA cm−2 in alkaline media, which is superior to most electrocatalysts previously reported in the literature. Combining experimental results with density functional theory (DFT) calculations, it is further revealed that the origin of high HER activity is mainly attributed to the synergy effects of single‐atom Ru doping and S vacancies and phase transition of local structure of MoS2, which efficiently tailors the electronic structure of SA‐Ru‐MoS2 and extremely reduces the energy barrier of the Volmer step and the adsorption/desorption of H* intermediate step. In short, this work provides a single‐atom doping strategy to transfer the inert MoS2 into the highly efficient electrocatalysts.

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