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This paper builds an aircraft simulation environment, and establishes a test model of an automated spin recovery algorithm based on proximal policy optimization (PPO) algorithm. Four kinds of network structures are designed, that are basis single stage, basis double stage, deep single stage and deep double stage, to explore the influence of network structure and recovery stage on spin recovery effect. A robustness test experiment is set up, and the algorithm is tested and the results are analyzed from the aspects of delay, error and height.

Intestinal stromal cells are known to modulate the propagation and differentiation of intestinal stem cells.sup.1,2. However, the precise cellular and molecular mechanisms by which this diverse stromal cell population maintains tissue homeostasis and repair are poorly understood. Here we describe a subset of intestinal stromal cells, named MAP3K2-regulated intestinal stromal cells (MRISCs), and show that they are the primary cellular source of the WNT agonist R-spondin 1 following intestinal injury in mice. MRISCs, which are epigenetically and transcriptomically distinct from subsets of intestinal stromal cells that have previously been reported.sup.3-6, are strategically localized at the bases of colon crypts, and function to maintain LGR5.sup.+ intestinal stem cells and protect against acute intestinal damage through enhanced R-spondin 1 production. Mechanistically, this MAP3K2 specific function is mediated by a previously unknown reactive oxygen species (ROS)-MAP3K2-ERK5-KLF2 axis to enhance production of R-spondin 1. Our results identify MRISCs as a key component of an intestinal stem cell niche that specifically depends on MAP3K2 to augment WNT signalling for the regeneration of damaged intestine. A subset of intestinal stromal cells that is regulated by the kinase MAP3K2 protects intestinal stem cells against injury by producing the WNT agonist R-spondin 1., Author(s): Ningbo Wu [sup.1] [sup.2] , Hongxiang Sun [sup.1] [sup.2] , Xiaoyun Zhao [sup.1] [sup.2] , Yao Zhang [sup.1] [sup.3] , Jianmei Tan [sup.1] [sup.2] , Yuanyuan Qi [sup.1] , [...]

The main reasons for the difficulty in curing and high recurrence rate of glioblastoma multiforme (GBM) include: 1. The difficulty of chemotherapy drugs in penetrating the blood-brain barrier (BBB) to target tumor cells; 2. The presence of glioma stem cells (GSCs) leading to chemotherapy resistance. Therefore, breaking through the limitations of the BBB and overcoming the drug resistance caused by GSCs are the main strategies to address this problem. This study presents our results on the development of lactoferrin (Lf)/CD133 antibody conjugated nanostructured lipid carriers (Lf/CD133-NLCS) for simultaneously targeting BBB and GSCs. Temozolomide (TMZ) loaded Lf/CD133-NLCS (Lf/CD133-NLCS-TMZ) exhibited high-efficiency in vitro anti-tumor effects toward malignant glioma cells (U87-MG) and GSCs, while demonstrating no significant toxicity to normal cells at concentrations lower than 200 μg ml -1 . The results of the in vitro targeting GBM study revealed a notably higher cellular uptake of Lf/CD133-NLCS-TMZ in U87-MG cells and GSCs in comparison to Lf/CD133 unconjugated counterpart (NLCS-TMZ). In addition, increased BBB permeability were confirmed for Lf/CD133-NLCS-TMZ compared to NLCS-TMZ both in vitro and in vivo . Taking together, Lf/CD133-NLCS-TMZ show great potential for dual targeting of BBB and GSCs, as well as GBM therapy based on this strategy., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)