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The HEAT repeat protein HPO-27 is a lysosome fission factor

Lysosomes are degradation and signalling centres crucial for homeostasis, development and ageing1. To meet diverse cellular demands, lysosomes remodel their morphology and function through constant fusion and fission2,3. Little is known about the molecular basis of fission. Here we identify HPO-27, a conserved HEAT repeat protein, as a lysosome scission factor in Caenorhabditis elegans. Loss of HPO-27 impairs lysosome fission and leads to an excessive tubular network that ultimately collapses. HPO-27 and its human homologue MROH1 are recruited to lysosomes by RAB-7 and enriched at scission sites. Super-resolution imaging, negative-staining electron microscopy and in vitro reconstitution assays reveal that HPO-27 and MROH1 self-assemble to mediate the constriction and scission of lysosomal tubules in worms and mammalian cells, respectively, and assemble to sever supported membrane tubes in vitro. Loss of HPO-27 affects lysosomal morphology, integrity and degradation activity, which impa

A potent fluorescent transmembrane HCl transporter perturbs cellular p by Mohamed Fares, Xin Wu et al

A series of fluorescent coumarin bis-ureas 1-4 have been synthesised, and their anion transport properties studied. The compounds function as highly potent HCl co-transport agents in lipid bilayer membranes. Single crystal X-ray diffraction of compound 1 showed antiparallel stacking of the coumarin rings, stabilised by hydrogen bonds. Binding studies, using 1H-NMR titration, showed moderate chloride binding in DMSO-d6/0.5% with 1 : 1 binding mode (for transporter 1) and 1 : 2 binding mode (host: guest, for transporters 2-4). We examined the cytotoxicity of compounds 1-4 against three cancer cell lines, lung adenocarcinoma (A549), colon adenocarcinoma (SW620) and breast adenocarcinoma (MCF-7). The most lipophilic transporter, 4 showed a cytotoxic effect against all three cancer cell lines. Cellular fluorescence studies showed compound 4 crossed the plasma membrane and localised in the cytoplasm after a short time. Interestingly, compound 4, lacking any lysosome targeting groups, was co-

Paeoniflorin Ameliorates BiPN by Reducing IL6 Levels and Regulating PA

The importance of the endosomal pathway for SARS-CoV-2 entry

Researchers demonstrated that combined inhibition of cell-surface-based and endosomal pathways completely blocked SARS-CoV-2 entry into mammalian cells.

[Full text] Near-Infrared Light-Triggered Thermosensitive Liposomes Modified with

6S 2. This molecule is water-soluble and can be encapsulated within the inner cavities of liposomes. IR820 is more stable at different temperatures and has longer tissue retention time and better biosecurity than ICG. 12 PTT can kill primary tumor cells but cannot eradicate metastatic tumor cells, whereas chemotherapy, as a systemic treatment, can kill primary and metastatic tumor cells. 13 Therefore, the combination of chemotherapy and PTT in the treatment of cancer has attracted considerable attention in basic research and clinical practice. Over the past few decades, scholars have studied many nanodrug delivery carriers, including liposomes, polymeric micelles, polymer-drug conjugates, and dendritic macromolecular nucleic acid nanoparticles, among which liposomes and polymer-drug conjugates are the dominant nanoparticles in clinical applications.

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