No abstract

As a common feature in a majority of malignant tumors, hypoxia has become the Achilles’ heel of photodynamic therapy (PDT). The development of type‐I photosensitizers that show hypoxia‐tolerant PDT efficiency provides a straightforward way to address this issue. However, type‐I PDT materials have rarely been discovered. Herein, a π‐conjugated molecule with A–D–A configuration, COi6‐4Cl, is reported. The H2O‐dispersible nanoparticle of COi6‐4Cl can be activated by an 880 nm laser, and displays hypoxia‐tolerant type I/II combined PDT capability, and more notably, a high NIR‐II fluorescence with a quantum yield over 5%. Moreover, COi6‐4Cl shows a negligible photothermal conversion effect. The non‐radiative decay of COi6‐4Cl is suppressed in the dispersed and aggregated state due to the restricted molecular vibrations and distinct intermolecular steric hindrance induced by its four bulky side chains. These features make COi6‐4Cl a distinguished single‐NIR‐wavelength‐activated phototheranostic material, which performs well in NIR‐II fluorescence‐guided PDT treatment and shows an enhanced in vivo anti‐tumor efficiency over the clinically approved Chlorin e6, by the equal stresses on hypoxia‐tolerant anti‐tumor therapy and deep‐penetration imaging. Therefore, the great potential of COi6‐4Cl in precise PDT cancer therapy against hypoxia challenges is demonstrated.

Abstract5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark that regulates gene expression. Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues. We found that 5hmC preferentially decorates gene bodies and outperforms gene body 5mC in reflecting gene expression. Approximately one-third of 5hmC peaks are tissue-specific differentially-hydroxymethylated regions (tsDhMRs), which are deposited in regions that potentially regulate the expression of nearby tissue-specific functional genes. In addition, tsDhMRs are enriched with tissue-specific transcription factors and may rewire tissue-specific gene expression networks. Moreover, tsDhMRs are associated with single-nucleotide polymorphisms identified by genome-wide association studies and are linked to tissue-specific phenotypes and diseases. Collectively, our results show the tissue-specific 5hmC landscape of the human genome and demonstrate that 5hmC serves as a fundamental regulatory element affecting tissue-specific gene expression programs and functions.