Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.

Phagocytes, including neutrophils and macrophages, have been suggested to function in a cooperative way in the initial phase of inflammatory responses, but their interaction and integration in the resolution of inflammation and tissue repair remain unclear. Here we show that neutrophils have crucial functions in liver repair by promoting the phenotypic conversion of pro-inflammatory Ly6C hi CX 3 CR1 lo monocytes/macrophages to pro-resolving Ly6C lo CX 3 CR1 hi macrophages. Intriguingly, reactive oxygen species (ROS), expressed predominantly by neutrophils, are important mediators that trigger this phenotypic conversion to promote liver repair. Moreover, this conversion is prevented by the depletion of neutrophils via anti-Ly6G antibody, genetic deficiency of granulocyte colony-stimulating factor, or genetic deficiency of NADPH oxidase 2 (Nox2). By contrast, adoptive transfer of WT rather than Nox2 −/− neutrophils rescues the impaired phenotypic conversion of macrophages in neutrophil-depleted mice. Our findings thus identify an intricate cooperation between neutrophils and macrophages that orchestrate resolution of inflammation and tissue repair.

This paper proposes a novel incremental training mode to address the problem of Deep Reinforcement Learning (DRL) based path planning for a mobile robot. Firstly, we evaluate the related graphic search algorithms and Reinforcement Learning (RL) algorithms in a lightweight 2D environment. Then, we design the algorithm based on DRL, including observation states, reward function, network structure as well as parameters optimization, in a 2D environment to circumvent the time-consuming works for a 3D environment. We transfer the designed algorithm to a simple 3D environment for retraining to obtain the converged network parameters, including the weights and biases of deep neural network (DNN), etc. Using these parameters as initial values, we continue to train the model in a complex 3D environment. To improve the generalization of the model in different scenes, we propose to combine the DRL algorithm Twin Delayed Deep Deterministic policy gradients (TD3) with the traditional global path planning algorithm Probabilistic Roadmap (PRM) as a novel path planner (PRM+TD3). Experimental results show that the incremental training mode can notably improve the development efficiency. Moreover, the PRM+TD3 path planner can effectively improve the generalization of the model.

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