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Liposome formulations by zwitterionic lipids (e.g., phosphatidyl choline (PC)) have been widely applied in the clinical translation of nanomedicines. However, poor bioorthogonality in the PC lipid backbone and limited cellular uptake potency significantly impede the development of a therapeutic strategy. Herein, we synthesized a novel bioorthogonal zwitterionic lipid named choline phosphate (CP), with reversed PC charge orientation via a phospholane derivative ring-opening reaction. CP lipids can assemble into liposomes with excellent biocompatibility and stable physical and chemical properties similar to PC liposomes. Due to supramolecular ionic pair interactions with the cell membrane, doxorubicin (Dox)-loaded CP liposomes (CP-Dox) were preferentially taken up and accumulated in cells compared to PC-Dox, which significantly enhanced the cytotoxicity in cancer cells and inhibited tumor growth. Furthermore, we determined the bioorthogonality of the CP lipids by conjugating folate in situ using a "click" reaction, which showed specificity in targeting treatment for breast cancer. Our studies provide a new proof of concept that functional liposomes can be designed at the molecular level. We also expect that CP lipids may have potential in other applications, including biosensors, antifouling coatings, cell membrane mimetic engineering, and artificial cells.

The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages. However, it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures. We show the activation of Kcnk5b is sufficient to activate several genes that are part of important development programs. We provide in vivo transplantation evidence that the activation of gene transcription is cell autonomous. We also show that Kcnk5b will induce the expression of different subsets of the tested developmental genes in different cultured mammalian cell lines, which may explain how one electrophysiological stimulus can coordinately regulate the allometric growth of diverse populations of cells in the fin that use different developmental signals. We also provide evidence that the post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity to scale the fin. Thus, we show how an endogenous bioelectric mechanism can be regulated to promote coordinated developmental signaling to generate and scale a vertebrate appendage.

Eight new marine steroids, characterized by either the presence of an aromatic ring or a cross-conjugated dienone system in ring A, were isolated from the Hainan soft coral Dendronephthya studeri Ridley. Their structures were elucidated on the basis of detailed spectroscopic analysis and by comparison of their NMR data with those reported in the literature.

Low temperature is an environmental stress factor that is always been applied in research on improving crop growth, productivity, and quality of crops. Polyunsaturated fatty acids (PUFAs) play an important role in cold tolerance, so its genetic manipulation of the PUFA contents in crops has led to the modification of cold sensitivity. In this study, we over-expressed an ω-3 fatty acid desaturase from Glycine max (GmFAD3A) drove by a maize ubiquitin promoter in rice. Compared to the wild type (ZH11), ectopic expression of GmFAD3A increased the contents of lipids and total PUFAs. Seed germination rates in GmFAD3A transgenic rice were enhanced under low temperature (15 °C). Moreover, cold tolerance and survival ratio were significantly improved in GmFAD3A transgenic seedlings. Malondialdehyde (MDA) content in GmFAD3A transgenic rice was lower than that in WT under cold stress, while proline content obviously increased. Meanwhile, the activities of superoxide dismutase (SOD), hydroperoxidase (CAT), and peroxidase (POD) increased substantially in GmFAD3A transgenic rice after 4 h of cold treatment. Taken together, our results suggest that GmFAD3A can enhances cold tolerance and the seed germination rate at a low temperature in rice through the accumulation of proline content, the synergistic increase of the antioxidant enzymes activity, which finally ameliorated the oxidative damage.

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