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Creators/Authors contains: "Li, Zhongyu"

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  1. Abstract

    Synergistically improving T-cell responsiveness is promising for favorable therapeutic outcomes in immunologically cold tumors, yet current treatments often fail to induce a cascade of cancer-immunity cycle for effective antitumor immunity. Gasdermin-mediated pyroptosis is a newly discovered mechanism in cancer immunotherapy; however, cleavage in the N terminus is required to activate pyroptosis. Here, we report a single-agent mRNA nanomedicine-based strategy that utilizes mRNA lipid nanoparticles (LNPs) encoding only the N-terminus of gasdermin to trigger pyroptosis, eliciting robust antitumor immunity. In multiple female mouse models, we show that pyroptosis-triggering mRNA/LNPs turn cold tumors into hot ones and create a positive feedback loop to promote antitumor immunity. Additionally, mRNA/LNP-induced pyroptosis sensitizes tumors to anti-PD-1 immunotherapy, facilitating tumor growth inhibition. Antitumor activity extends beyond the treated lesions and suppresses the growth of distant tumors. We implement a strategy for inducing potent antitumor immunity, enhancing immunotherapy responses in immunologically cold tumors.

     
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  2. Navigating a large-scaled robot in unknown and cluttered height-constrained environments is challenging. Not only is a fast and reliable planning algorithm required to go around obstacles, the robot should also be able to change its intrinsic dimension by crouching in order to travel underneath height-constrained regions. There are few mobile robots that are capable of handling such a challenge, and bipedal robots provide a solution. However, as bipedal robots have nonlinear and hybrid dynamics, trajectory planning while ensuring dynamic feasibility and safety on these robots is challenging. This paper presents an end-to-end autonomous navigation framework which leverages three layers of planners and a variable walking height controller to enable bipedal robots to safely explore height-constrained environments. A vertically actuated spring-loaded inverted pendulum (vSLIP) model is introduced to capture the robot’s coupled dynamics of planar walking and vertical walking height. This reduced-order model is utilized to optimize for long-term and short-term safe trajectory plans. A variable walking height controller is leveraged to enable the bipedal robot to maintain stable periodic walking gaits while following the planned trajectory. The entire framework is tested and experimentally validated using a bipedal robot Cassie. This demonstrates reliable autonomy to drive the robot to safely avoid obstacles while walking to the goal location in various kinds of height-constrained cluttered environments.

     
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