BackgroundImmune checkpoint inhibitors (ICIs), including anti-PD-1 therapy, have limited efficacy in patients with microsatellite stable (MSS) colorectal cancer (CRC). Interleukin 17A (IL-17A) activity leads to a protumor microenvironment, dependent on its ability to induce the production of inflammatory mediators, mobilize myeloid cells and reshape the tumor environment. In the present study, we aimed to investigate the role of IL-17A in resistance to antitumor immunity and to explore the feasibility of anti-IL-17A combined with anti-PD-1 therapy in MSS CRC murine models.MethodsThe expression of programmed cell death-ligand 1 (PD-L1) and its regulation by miR-15b-5p were investigated in MSS CRC cell lines and tissues. The effects of miR-15b-5p on tumorigenesis and anti-PD-1 treatment sensitivity were verified both in vitro and in colitis-associated cancer (CAC) and APCmin/+ murine models. In vivo efficacy and mechanistic studies were conducted using antibodies targeting IL-17A and PD-1 in mice bearing subcutaneous CT26 and MC38 tumors.ResultsEvaluation of clinical pathological specimens confirmed that PD-L1 mRNA levels are associated with CD8+ T cell infiltration and better prognosis. miR-15b-5p was found to downregulate the expression of PD-L1 at the protein level, inhibit tumorigenesis and enhance anti-PD-1 sensitivity in CAC and APCmin/+ CRC models. IL-17A led to high PD-L1 expression in CRC cells through regulating the P65/NRF1/miR-15b-5p axis. Combined IL-17A and PD-1 blockade had efficacy in CT26 and MC38 tumors, with more cytotoxic T lymphocytes cells and fewer myeloid-derived suppressor cells in tumors.ConclusionsIL-17A increases PD-L1 expression through the p65/NRF1/miR-15b-5p axis and promotes resistance to anti-PD-1 therapy. Blocking IL-17A improved the efficacy of anti-PD-1 therapy in MSS CRC murine models. IL-17A might serve as a therapeutic target to sensitize patients with MSS CRC to ICI therapy.

Graphene (Gr) has been made of various forms used for repairing peripheral nerve injury with favorable electroactivity, however, graphene-based scaffolds in peripheral nerve regeneration are still rarely reported due to the difficulty of realizing uniform dispersion of graphene and electroactive materials at nanoscale as well as lacking biocompatibility. In this paper, graphene-silk fibroin (SF) composite nanofiber membranes with different mass ratios were prepared via electrospinning. Microscopic observation revealed that electrospun Gr/SF membranes had a nanofibrous structure. Electrochemical analysis provided electroactivity characterization of the Gr/SF membranes. The physiochemical results showed that the physiochemical properties of electrospun Gr/SF membranes could be changed by varying Gr concentration. Swelling ratio and contact angle measurements confirmed that electrospun Gr/SF membranes possessed large absorption capacity and hydrophilic surface, and the mechanical property was improved with increasing Gr concentration. Additionally, in-vitro cytotoxicity with L929 revealed that all the electrospun Gr/SF membranes are biocompatible. Moreover, the morphology and quantity showed that the membranes supported the survival and growth of the cultured Schwann cells. Collectively, all of the results suggest that the electrospun Gr/SF membranes combine the excellent electrically conductivity and mechanical strength of the graphene with biocompatibility property of silk to mimic the natural neural cell micro-environment for nerve development.

Timely administration of emergency therapeutics is critical for patients with sudden-onset illnesses. In article number 2208648, Haojian Lu, Jicheng Yu, Zhen Gu, and co-workers develop an unmanned aerial vehicle (UAV)-mediated first-aid system (uFAST), which enables the autonomous administration of emergency therapeutics via a UAV without the involvement of an additional or conscious person to achieve timely first aid.

The selective catalytic reduction of nitrogen oxide with methane (CH4–SCR) has been considered as an alternative technology for the simultaneous removal of NO x and CH4, and one of the efficient catalysts for this reaction is Co-exchanged SSZ-13 (Co-SSZ-13) zeolite catalyst. However, the preparation of the Co-SSZ-13 zeolite catalyst is costly due to the use of an expensive organic template and Co exchange. We demonstrate here the design of a low-cost cobalt–amine complex (Co–DETA) as a novel structure-directing agent (SDA) for the one-pot synthesis of Co-SSZ-13 zeolite with the assistance of theoretical calculations. Physicochemical characterizations including X-ray diffraction, scanning electron microscopy, N2 sorption, and magic-angle spinning nuclear magnetic resonance show that the Co-SSZ-13 zeolite has good crystallinity, a cubic morphology, a high surface area, and four-coordinated aluminum species. Furthermore, thermogravimetry–differential thermal analysis, Fourier transform infrared spectroscopy, and diffuse reflectance ultraviolet–visible spectroscopy confirm that the Co–DETA complex acts as a SDA for the synthesis of Co-SSZ-13 zeolite. More importantly, the Co-SSZ-13 zeolite exhibits good catalytic performance in the CH4–SCR reaction with 10% H2O in the feed gas stream. The efficient and facile synthesis of Co-SSZ-13 zeolite plus its good catalytic performance might offer a good opportunity for its industrial applications in the future.

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