28Rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the 29 ability to biosynthesize C 20-22 long-chain polyunsaturated fatty acids (LC-PUFA) from 30 C 18 PUFA precursors, which is generally absent or low in marine teleosts. Thus, 31 understanding the molecular basis of LC-PUFA biosynthesis in rabbitfish will 32 contribute to efforts aimed at optimizing LC-PUFA biosynthesis in teleosts, especially 33 marine species. In the present study, the importance of the transcription factors liver X 34 receptor (Lxr) and sterol regulatory element-binding protein 1 (Srebp1) in regulation 35 of LC-PUFA biosynthesis in rabbitfish was investigated. First, full-length cDNAs of 36Lxr and Srebp1 were cloned and characterized. The

Activation of the IRE-1/XBP-1 pathway is related to many human diseases. Coumarin-based derivatives acting as both IRE-1 inhibitors and bright fluorophores are highly desirable to establish an integrated fluorescent inhibitor system. Here, we take insights into the aqueous stability of a photocaged IRE-1 inhibitor PC-D-F07 through a structure activity relationship. The substituent effects indicate that the electron-withdrawing −NO 2 moiety in the photocage combined with the tricyclic coumarin fluorophore contribute to the structural stability of PC-D-F07. To optimize the photocage of PC-D-F07, we incorporate a 1-ethyl-2nitrobenzyl or 2-nitrobenzyl photolabile moiety on the hydroxyl group of the IRE-1 inhibitor to generate RF-7 and RF-8. Upon photoactivation, both RF-7 and RF-8 present an increased fluorescence response, sequentially enabling the unlocking of the ortho-1,3-dioxane acetal for the release of active IRE-1 inhibitors. Moreover, RF-7 exhibits a high repolarization ratio of converting M2-type tumor-associated macrophages (M2-TAMs) to M1-type immuneresponsive macrophages. This provides a novel prodrug strategy of modulating druggable fluorophore backbones to achieve spatiotemporally controllable drug release for precise cancer treatment.

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