Design and Reality-Based Modeling Optimization of a Flexible Passive Joint Paddle for Swimming Robots.

Rowing motion with paired propellers is an essential actuation mechanism for swimming robots. Previous work in this field has typically employed flexible propellers to generate a net thrust or torque by using changes in the compliance values of flexible structures under the influence of a fluid. The low stiffness values of the flexible structures restrict the upper limit of the oscillation frequency and amplitude, resulting in slow swimming speeds. Furthermore, complex coupling between the fluid and the propeller reduce the accuracy of flexible propeller simulations. A design of a flexible passive joint paddle was proposed in this study, and a dynamics model and simulation of the paddle were experimentally verified. In order to optimize the straight swimming speed, a data-driven model was proposed to improve the simulation accuracy. The effects of the joint number and controller parameters on the robot's straight swimming speed were comprehensively investigated. The multi-joint paddle exhibited significantly improved thrust over the single-joint paddle in a symmetric driving mode. The data-driven model reduced the total error of the simulated data of the propulsive force in the range of control parameters to 0.51%. Swimming speed increased by 3.3 times compared to baseline. These findings demonstrate the utility of the proposed dynamics and data-driven models in the multi-objective design of swimming robots.

Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints.

Immune checkpoint inhibitors (ICIs), Ipilimumab, Nivolumab, Pembrolizumab and Atezolizumab, have been applied in anti-tumor therapy and demonstrated exciting performance compared to conventional treatments. However, the unsatisfactory response rates, high recurrence and adaptive resistance limit their benefits. Metabolic reprogramming appears to be one of the crucial barriers to immunotherapy. The deprivation of required nutrients and altered metabolites not only promote tumor progression but also confer dysfunction on immune cells in the tumor microenvironment (TME). Glycolysis plays a central role in metabolic reprogramming and immunoregulation in the TME, and many therapies targeting glycolysis have been developed, and their combinations with ICIs are in preclinical and clinical trials. Additional attention has been paid to the role of amino acids, lipids, nucleotides and mitochondrial biogenesis in metabolic reprogramming and clinical anti-tumor therapy. This review attempts to describe reprogramming metabolisms within tumor cells and immune cells, from the aspects of glycolysis, amino acid metabolism, lipid metabolism, nucleotide metabolism and mitochondrial biogenesis and their impact on immunity in the TME, as well as the significance of targeting metabolism in anti-tumor therapy, especially in combination with ICIs. In particular, we highlight the expression mechanism of programmed cell death (ligand) 1 [PD-(L)1] in tumor cells and immune cells under reprogramming metabolism, and discuss in detail the potential of targeting key metabolic pathways to break resistance and improve the efficacy of ICIs based on results from current preclinical and clinical trials. Besides, we draw out biomarkers of potential predictive value in ICIs treatment from a metabolic perspective.