The authors declare that they have no conflicts of interest with the contents of this article. This article contains Figs. S1-S6 and Tables S1 and S2. The RNA-seq, ATAC-seq, and ChIP-seq data reported in this paper can be assessed under GEO GSE132970.

We report a new method for facile synthesis of block and star copolymers composed of helical poly(phenyl isocyanide) and polyacrylate segments via combination of Pd(II)initiated isocyanide polymerization and reversible addition− fragmentation chain transfer (RAFT) controlled radical polymerization. First, an alkyne−Pd(II) complex containing benzyl trithiocarbonate substituent was designed and synthesized. The Pd(II) moiety of the complex can catalyzed the living polymerization of phenyl isocyanides, while the benzyl trithiocarbonate unit can be used as a chain transfer agent for RAFT polymerization. Upon combination of the two living polymerizations, a series of block copolymers containing poly(phenyl isocyanide) and polyacrylate, poly(aryl vinyl) blocks with expected molecular weights (M n s) and narrow molecular weight distributions (M w /M n s) can be facilely prepared under controlled manner. Some of these block copolymers exhibited interesting self-assembly and stimuli-responsive properties. Taking advantage of this synthetic approach, core cross-linked star block copolymer carrying polyacrylate-block-polyisocyanide arms can be readily prepared through the copolymerization with a cross-linker, ethylene glycol dimethacrylate. Moreover, miktoarm star copolymers carrying helical polyisocyanides and polyacrylates arms can also be prepared under controlled manner.

In this manuscript, we designed and synthesized three core cross-linked micelles (M-5L, P-5L, and P-5D) with redox-responsive disulfide bonds in the core and carrying optically active helical polyisocyanide arms. Their arms were different in the helicity of the main chain and the chirality of the side groups. These micelles showed excellent redox-responsiveness to reducing agent. However, because of the different chiralities of the arms, the three micelles exhibited different performances in drug delivery and controlled release. The M-5L micelle carrying left-handed helical arms showed better therapeutic effect than the other two due to the rapid cell membrane permeability.

The class III PI3-kinase (PIK3C3) is an enzyme responsible for the generation of phosphatidylinositol 3-phosphate (PI3P), a critical component of vesicular membrane. Here, we report that PIK3C3 deficiency in zebrafish results in intestinal injury and inflammation. In pik3c3 mutants, gut tube forms but fails to be maintained. Gene expression analysis reveals that barrier-function-related inflammatory bowel disease (IBD) susceptibility genes (e-cadherin, hnf4a, ttc7a) are suppressed, while inflammatory response genes are stimulated in the mutants. Histological analysis shows neutrophil infiltration into mutant intestinal epithelium and the clearance of gut microbiota. Yet, gut microorganisms appear dispensable as mutants cultured under germ-free condition have similar intestinal defects. Mechanistically, we show that PIK3C3 deficiency suppresses the formation of PI3P and disrupts the polarized distribution of cell-junction proteins in intestinal epithelial cells. These results not only reveal a role of PIK3C3 in gut homeostasis, but also provide a zebrafish IBD model.