A series of novel benzo [c][1,2,5]oxadiazole derivatives were designed, synthesized, and biologically evaluated as inhibitors of PD-L1. Among them, compound L7 exhibited 1.8 nM IC 50 value in a homogeneous time-resolved fluorescence (HTRF) assay, which was 20-fold more potent than the lead compound BMS-1016. In the surface plasmon resonance (SPR) assay, L7 bound to human PD-L1 (hPD-L1) with a K D value of 3.34 nM, without showing any binding to hPD-1. In the cell-based coculture assay, L7 blocked PD-1/PD-L1 interaction with an EC 50 value of 375 nM, while BMS-1016 had an EC 50 value of 2075 nM. Moreover, compound L24, an ester prodrug of L7, was orally bioavailable and displayed significant antitumor effects in tumor models of syngeneic and PD-L1 humanized mice. Mechanistically, L24 exhibited significant in vivo antitumor effects probably through promoting antitumor immunity. Together, this series of benzoxadiazole PD-L1 inhibitors holds promise for tumor immunotherapy. Preclinical trials with selected compounds are ongoing in our laboratory.

The conventional initial alignment algorithms are invalid in the polar region. This is caused by the rapid convergence of the Earth meridians in the high-latitude areas. However, the initial alignment algorithms are important for the accurate navigation of Unmanned Underwater Vehicles. The polar transversal initial alignment algorithm is proposed to overcome this problem. In the polar transversal initial alignment algorithm, the transversal geographic frame is chosen as the navigation frame. The polar region in the conventional frames is equivalent to the equatorial region in the transversal frames. Therefore, the polar transversal initial can be effectively applied in the polar region. According to the complex environment in the polar region, a large misalignment angle is considered in this paper. Based on the large misalignment angle condition, the non-linear dynamics models are established. In addition, the simplified unscented Kalman filter (UKF) is chosen to realize the data fusion. Two comparison simulations and an experiment are performed to verify the performance of the proposed algorithm. The simulation and experiment results indicate the validity of the proposed algorithm, especially when large misalignment angles occur.

In a complex underwater environment, finding a viable, collision-free path for an autonomous underwater vehicle (AUV) is a challenging task. The purpose of this paper is to establish a safe, real-time, and robust method of collision avoidance that improves the autonomy of AUVs. We propose a method based on active sonar, which utilizes a deep reinforcement learning algorithm to learn the processed sonar information to navigate the AUV in an uncertain environment. We compare the performance of double deep Q-network algorithms with that of a genetic algorithm and deep learning. We propose a line-of-sight guidance method to mitigate abrupt changes in the yaw direction and smooth the heading changes when the AUV switches trajectory. The different experimental results show that the double deep Q-network algorithms ensure excellent collision avoidance performance. The effectiveness of the algorithm proposed in this paper was verified in three environments: random static, mixed static, and complex dynamic. The results show that the proposed algorithm has significant advantages over other algorithms in terms of success rate, collision avoidance performance, and generalization ability. The double deep Q-network algorithm proposed in this paper is superior to the genetic algorithm and deep learning in terms of the running time, total path, performance in avoiding collisions with moving obstacles, and planning time for each step. After the algorithm is trained in a simulated environment, it can still perform online learning according to the information of the environment after deployment and adjust the weight of the network in real-time. These results demonstrate that the proposed approach has significant potential for practical applications.

The spatial path following control problem of autonomous underwater vehicles (AUVs) is addressed in this paper. In order to realize AUVs’ spatial path following control under systemic variations and ocean current, three adaptive neural network controllers which are based on the Lyapunov stability theorem are introduced to estimate uncertain parameters of the vehicle’s model and unknown current disturbances. These controllers are designed to guarantee that all the error states in the path following system are asymptotically stable. Simulation results demonstrated that the proposed controller was effective in reducing the path following error and was robust against the disturbances caused by vehicle's uncertainty and ocean currents.

Due to its highly autonomy, the strapdown inertial navigation system (SINS) is widely used in unmanned underwater vehicles (UUV) navigation. Initial alignment is crucial because the initial alignment results will be used as the initial SINS value, which might affect the subsequent SINS results. Due to the rapid convergence of Earth meridians, there is a calculation overflow in conventional initial alignment algorithms, making conventional initial algorithms are invalid for polar UUV navigation. To overcome these problems, a polar initial alignment algorithm for UUV is proposed in this paper, which consists of coarse and fine alignment algorithms. Based on the principle of the conical slow drift of gravity, the coarse alignment algorithm is derived under the grid frame. By choosing the velocity and attitude as the measurement, the fine alignment with the Kalman filter (KF) is derived under the grid frame. Simulation and experiment are realized among polar, conventional and transversal initial alignment algorithms for polar UUV navigation. Results demonstrate that the proposed polar initial alignment algorithm can complete the initial alignment of UUV in the polar region rapidly and accurately.