Diabetes is a complex metabolic syndrome that is characterized by prolonged high blood glucose levels and frequently associated with life-threatening complications. Epidemiological studies have suggested that diabetes is also linked to an increased risk of cancer. High glucose levels may be a prevailing factor that contributes to the link between diabetes and cancer, but little is known about the molecular basis of this link and how the high glucose state may drive genetic and/or epigenetic alterations that result in a cancer phenotype. Here we show that hyperglycaemic conditions have an adverse effect on the DNA 5-hydroxymethylome. We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, thereby stabilizing the tumour suppressor. Increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5-hydroxymethylcytosine (5hmC) and the tumour suppressive function of TET2 in vitro and in vivo. Treatment with the anti-diabetic drug metformin protects AMPK-mediated phosphorylation of serine 99, thereby increasing TET2 stability and 5hmC levels. These findings define a novel 'phospho-switch' that regulates TET2 stability and a regulatory pathway that links glucose and AMPK to TET2 and 5hmC, which connects diabetes to cancer. Our data also unravel an epigenetic pathway by which metformin mediates tumour suppression. Thus, this study presents a new model for how a pernicious environment can directly reprogram the epigenome towards an oncogenic state, offering a potential strategy for cancer prevention and treatment.

Infections are regarded as the most severe complication associated with human health, which are urgent to be solved. Stimuli-responsive materials are appealing therapeutic platforms for antibacterial treatments, which provide great potential for accurate theranostics. In this review, the advantages, the response mechanisms, and the key design principles of stimuli-responsive antibacterial materials are highlighted. The biomedical applications, the current challenges, and future directions of stimuli-responsive antibacterial materials are also discussed. First, the categories of stimuli-responsive antibacterial materials are comprehensively itemized based on different sources of stimuli, including external physical environmental stimuli (e.g., temperature, light, electricity, salt, etc.) and bacterial metabolites stimuli (e.g., acid, enzyme, redox, etc.). Second, structural characteristics, design principles, and biomedical applications of the responsive materials are discussed, and the underlying interrelationships are revealed. The molecular structures and design principles are closely related to the sources of stimuli. Finally, the challenging issues of stimuli-responsive materials are proposed. This review will provide scientific guidance to promote the clinical applications of stimuli-responsive antibacterial materials.

Three-dimensional (3D) bioprinting has emerged as a promising scaffold fabrication strategy for tissue engineering with excellent control over scaffold geometry and microstructure. Nanobiomaterials as bioinks play a key role in manipulating the cellular microenvironment to alter its growth and development. This review first introduces the commonly used nanomaterials in tissue engineering scaffolds, including natural polymers, synthetic polymers, and polymer derivatives, and reveals the improvement of nanomaterials on scaffold performance. Second, the 3D bioprinting technologies of inkjet-based bioprinting, extrusion-based bioprinting, laser-assisted bioprinting, and stereolithography bioprinting are comprehensively itemized, and the advantages and underlying mechanisms are revealed. Then the convergence of 3D bioprinting and nanotechnology applications in tissue engineering scaffolds, such as bone, nerve, blood vessel, tendon, and internal organs, are discussed. Finally, the challenges and perspectives of convergence of 3D bioprinting and nanotechnology are proposed. This review will provide scientific guidance to develop 3D bioprinting tissue engineering scaffolds by nanotechnology.

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