A Multi-Agent Deep Reinforcement Learning-Based Popular Content Distribution Scheme in Vehicular Networks.

The Internet of Vehicles (IoV) enables vehicular data services and applications through vehicle-to-everything (V2X) communications. One of the key services provided by IoV is popular content distribution (PCD), which aims to quickly deliver popular content that most vehicles request. However, it is challenging for vehicles to receive the complete popular content from roadside units (RSUs) due to their mobility and the RSUs' constrained coverage. The collaboration of vehicles via vehicle-to-vehicle (V2V) communications is an effective solution to assist more vehicles to obtain the entire popular content at a lower time cost. To this end, we propose a multi-agent deep reinforcement learning (MADRL)-based popular content distribution scheme in vehicular networks, where each vehicle deploys an MADRL agent that learns to choose the appropriate data transmission policy. To reduce the complexity of the MADRL-based algorithm, a vehicle clustering algorithm based on spectral clustering is provided to divide all vehicles in the V2V phase into groups, so that only vehicles within the same group exchange data. Then the multi-agent proximal policy optimization (MAPPO) algorithm is used to train the agent. We introduce the self-attention mechanism when constructing the neural network for the MADRL to help the agent accurately represent the environment and make decisions. Furthermore, the invalid action masking technique is utilized to prevent the agent from taking invalid actions, accelerating the training process of the agent. Finally, experimental results are shown and a comprehensive comparison is provided, which demonstrates that our MADRL-PCD scheme outperforms both the coalition game-based scheme and the greedy strategy-based scheme, achieving a higher PCD efficiency and a lower transmission delay.

Changes in heparan sulfate sulfotransferases and cell-surface heparan sulfate during SKM-1 cells granulocytic differentiation and A549 cells epithelial-mesenchymal transition.

Heparan sulfate (HS) with various sulfation patterns is one of important modulators of cancer cell fate through interacting with numerous growth factors. Here we found HS 2-O sulfotransferase 1 (HS2ST1) was downregulated at both mRNA and protein levels during granulocytic differentiation of SKM-1 leukemia cells and also HS (glucosamine) 3-O sulfotransferase 3A (HS3ST3A) in epithelial-mesenchymal transition (EMT) of A549 lung cancer cells, meanwhile, cell-surface HS recognized by anti-HS antibody was also changed in both cancer cell lines. Further, HS3ST3A was negatively correlated with the in vitro cell metastasis capability of A549 cells confirmed by RNA interference technology, wound-healing assay and in vitro Matrigel invasion assay. Together, specific HS sulfotransferases may serve as molecular markers and targets for cancer treatment.

Heparan sulfate 6-O-sulfotransferase 3 is involved in bone marrow mesenchymal stromal cell osteogenic differentiation|.

The roles of sugar chains such as heparan sulfate (HS) in stem cell self-renewal and differentiation are poorly understood. HS is a sugar chain with linear sulfated polyanionic disaccharide repeating structures that interact with many proteins, including structural proteins in the extracellular matrix and growth factors and their receptors. Thus, unraveling the role of HS in stem cell self-renewal and differentiation could provide new insights and technical routes in clinical stem cell applications. Here, we purified rat bone marrow mesenchymal stromal cells (BMMSCs) by density gradient centrifugation, analyzed mesenchymal stromal cell surface stemness marker expression by flow cytometry, and identified the sulfotransferases responsible for sulfation ester modification of HS. An osteogenic differentiation model was established by chemical induction reagents and confirmed via alkaline phosphatase (ALP) activity detection and the expression of the osteogenic differentiation markers Runx2 and Ocn. The expression profiles of HS sulfotransferases in rat BMMSCs before and after osteogenic induction were detected by RT-PCR and Western blot. Cell spheroids were formed in both control and osteogenic culture systems when BMMSCs were grown to high confluence. We determined that this type of cell spheroid was a highly calcified nodule by histochemical staining. Among all the sulfotransferases examined, heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) mRNA and protein were upregulated in these calcified cell spheroids. HS6ST3 knockdown BMMSCs were established with RNA interference, and they had significantly lower ALP activity and decreased expression of the osteogenic differentiation markers Runx2 and Ocn. These findings suggest that HS6ST3 is involved in BMMSC differentiation, and new glycotherapeutic-based technologies could be developed in the future.

Preparation of heparan sulfate-like polysaccharide and application in stem cell chondrogenic differentiation.

Heparan sulfate is a component of the extracellular matrix (ECM) that modulates individual development and cell growth through its interaction with growth factors. Structurally, heparan sulfate consists of repeating linear sulfated poly-anionic disaccharide structures. The K5 polysaccharide has the same structure as heparosan, and is the capsular polysaccharide of Escherichia coli K5 strain which serves as a precursor in heparin and heparan sulfate biosynthesis. Here, we prepared sulfated K5 polysaccharides that are structurally similar to heparan sulfate and investigated their biocompatibility and bioactivity in stem cell chondrogenic differentiation. Briefly, sulfation groups were added to -NH- and/or -OH of a precursor heparosan and the modified heparosan was qualitatively analyzed by FT-IR, (1)H NMR, and (13)C NMR techniques. Cell viability was not significantly affected by the sulfated K5 capsular polysaccharide. Relative mRNA expression of the chondrogenic differentiation marker COL2A1 was significantly upregulated in cells treated with the N,O-sulfated K5 polysaccharide confirming that the sulfated K5 capsular polysaccharide is able to stimulate chondrogenic differentiation. The main sulfation pattern for chondrogenic activity is N,6-O sulfation and the activity was not proportional to the sulfation level. This type of mimic was prepared in nearly a gram scale, supporting further structural study and 3 dimension stem cell culture. Together, the results of this study show that sulfated K5 capsular polysaccharides are able to stimulate chondrogenic differentiation without affecting cell viability.