Cancer-induced immune responses affect tumor progression and therapeutic response. In multiple murine models and clinical datasets, we identified large variations of neutrophils and macrophages, which define “immune subtypes” of triple negative breast cancer (TNBC) including neutrophil-enriched (NES) and macrophage-enriched subtypes (MES). Different tumor-intrinsic pathways and mutual regulation between macrophages/monocytes and neutrophils contribute to the development of dichotomous myeloid compartment. MES contains predominantly macrophages that are CCR2-dependent and exhibit variable responses to immune checkpoint blockade (ICB). NES exhibits systemic and local accumulation of immunosuppressive neutrophils (or granulocytic myeloid-derived suppressor cells (gMDSCs), is resistant to ICB, and contains a minority of macrophages that appear to be unaffected by CCR2 knockout. A MES-to-NES conversion mediated acquired ICB resistance of initially sensitive MES models. Our results demonstrate diverse myeloid cell frequencies, functionality, and potential roles in immunotherapies, and highlight the need to better understand the inter-patient heterogeneity of the myeloid compartment.
We report a facile synthetic protocol to prepare mesoporous FeS without the aid of hard template as an electrocatalyst for the hydrogen evolution reaction (HER). The mesoporous FeS materials with high surface area were successfully prepared by a sol-gel method following a sulfurization treatment in an HS atmosphere. A remarkable HER catalytic performance was achieved with a low overpotential of 96 mV at a current density of 10 mA·cm and a Tafel slope of 78 mV per decade under alkaline conditions (pH 13). The theoretical calculations indicate that the excellent catalytic activity of mesoporous FeS is attributed to the exposed (210) facets. The mesoporous FeS material might be a promising alternative to the Pt-based electrocatalysts for water splitting.
A unique approach for the synthesis of nonstoichiometric, mesoporous molybdenum oxide (MoO 3-x ) with nanosized crystalline walls by using a soft template (PEO-b -PS) synthesis method is introduced. The as-synthesized mesoporous MoO 3-x is very active and stable (durability > 12 h) for the electrochemical hydrogen evolution reaction (HER) under both acidic and alkaline conditions. The intrinsic MoO 3 serves as an HER electrocatalyst without the assistance of carbon materials, noble metals, or MoS 2 materials. The results from transmission electron microscopy and N 2 sorption techniques show that the as-synthesized mesoporous MoO 3-x has large accessible pores (20-40 nm), which are able to facilitate mass transport and charge transfer during HER. In terms of X-ray diffraction, X-ray photoelectron spectroscopy, temperature-programmed oxidation, and diffusive refl ectance UV-vis spectroscopy, the mesoporous MoO 3-x exhibits mixed oxidation states (Mo 5+ , Mo 6+ ) and an oxygen-defi cient structure. The as-synthesized MoO 3-x only requires a low overpotential (≈0.14 V) to achieve a 10 mA cm −2 current density in 0.1 M KOH and the Tafel slope is as low as 56 mV dec −1 . Density functional theory calculations demonstrate a change of electronic structure and the possible reaction pathway of HER. Oxygen vacancies and mesoporosity serve as key factors for excellent performance.
Biohybrid microswimmers have recently shown to be able to actively perform in targeted delivery and in vitro biomedical applications. However, more envisioned functionalities of the microswimmers aimed at in vivo treatments are still challenging. A photosynthetic biohybrid nanoswimmers system (PBNs), magnetic engineered bacteria-Spirulina platensis, is utilized for tumor-targeted imaging and therapy. The engineered PBNs is fabricated by superparamagnetic magnetite (Fe 3 O 4 NPs) via a dip-coating process, enabling its tumor targeting ability and magnetic resonance imaging property after intravenous injection. It is found that the PBNs can be used as oxygenerator for in situ O 2 generations in hypoxic solid tumors through photosynthesis, modulating the tumor microenvironment (TME), thus improving the effectiveness of radiotherapy (RT). Furthermore, the innate chlorophyll released from the RT-treated PBNs, as a photosensitizer, can produce cytotoxic reactive oxygen species under laser irradiation to achieve photodynamic therapy. Excellent tumor inhibition can be realized by the combined multimodal therapies. The PBNs also possesses capacities of chlorophyll-based fluorescence and photoacoustic imaging, which can monitor the tumor therapy and tumor TME environment. These intriguing properties of the PBNs provide a promising microrobotic platform for TME hypoxic modulation and cancer theranostic applications.
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