The updated landscape of tumor microenvironment and drug repurposing

Accumulating evidence shows that cellular and acellular components in tumor microenvironment(TME)can reprogram tumor initiation,growth,invasion,metastasis,and response to therapies.Cancer research and treatment have switched from a cancercentric model to a TME-centric one,considering the increasing significance of TME in cancer biology.Nonetheless,the clinical efficacy of therapeutic strategies targeting TME,especially the specific cells or pathways of TME,remains unsatisfactory.Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods.Herein,we present an updated image of TME with emphasis on hypoxic niche,immune microenvironment,metabolism microenvironment,acidic niche,innervated niche,and mechanical microenvironment.We then summarize conventional drugs including aspirin,celecoxib,β-adrenergic antagonist,metformin,and statin in new antitumor application.These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice.We also provide our outlook on directions and potential applications of TME theory.This review depicts a comprehensive and vivid landscape of TME from biology to treatment.

Lubricant skin on diverse biomaterials with complex shapes via polydopamine-mediated surface functionalization for biomedical applications

Implantable biomedical devices require an anti-biofouling,mechanically robust,low friction surface for a prolonged lifespan and improved performance.However,there exist no methods that could provide uniform and effective coatings for medical devices with complex shapes and materials to prevent immune-related side effects and thrombosis when they encounter biological tissues.Here,we report a lubricant skin(L-skin),a coating method based on the application of thin layers of bio-adhesive and lubricant-swellable perfluoropolymer that impart anti-biofouling,frictionless,robust,and heat-mediated self-healing properties.We demonstrate biocompatible,mechanically robust,and sterilization-safe L-skin in applications of bioprinting,microfluidics,catheter,and long and narrow medical tubing.We envision that diverse applications of L-skin improve device longevity,as well as anti-biofouling attributes in biomedical devices with complex shapes and material compositions.

Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells

The methylcytosine dioxygenases TET proteins （TET1, TET2, and TET3） play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA （valproic acid）-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neu- ronal differentiation of Neuro2a cells. Interestingly, the inducing activity of TET protein is independent of its enzymatic activity. Our previous studies have demon- strated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells. Furthermore, we revealed that TET1 could positively regulate srGAP3 expression independent of its catalytic activity, and srGAP3 is required for TET-mediated neuronal differentiation of Neuro2a cells. The results presented here may facilitate better understanding of the role of TET proteins in neuronal differentiation, and provide a possible therapy target for neuroblastoma.