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Abstract The elevated glutathione (GSH) level in solid tumors has been used as a major hallmark for GSH‐responsive nanoparticles to enhance targeting efficiency and specificity. Meanwhile, GSH is mainly synthesized inside the hepatocytes of the liver in the body and constantly released into the blood through hepatic GSH efflux to regulate redox potential of the entire body. However, it remains largely unknown how this hepatic GSH efflux affects the tumor targeting of GSH‐responsive nanoparticles. Herein, we report that depletion of hepatic GSH enhanced the tumor targeting of GSH‐responsive indocyanine green‐conjugated Au₂₅nanoclusters coated with 18 GSH ligand (ICG‐Au₂₅SG₁₈). The dissociation of ICG from Au₂₅SG₁₈by the hepatic GSH through thiol‐exchange reaction and the subsequent hepatobiliary clearance of the detached ICG were slowed down by GSH depletion, which in turn prolonged the blood circulation of intact ICG‐Au₂₅SG₁₈and enhanced its tumor targeting. Our work highlights glutathione‐mediated crosstalk between the liver and tumor, in addition to well‐known Kupffer cell‐mediated uptake, in the tumor targeting of engineered nanoparticles, which could be modulated to enhance targeting efficiency and specificity of cancer nanomedicines while reducing their nonspecific accumulation. 

Previously, we showed that the nuclear import receptor Importin-9 wraps around the H2A-H2B core to chaperone and transport it from the cytoplasm to the nucleus. However, unlike most nuclear import systems where RanGTP dissociates cargoes from their importins, RanGTP binds stably to the Importin-9•H2A-H2B complex, and formation of the ternary RanGTP•Importin-9•H2A-H2B complex facilitates H2A-H2B release to the assembling nucleosome. It was unclear how RanGTP and the cargo H2A-H2B can bind simultaneously to an importin, and how interactions of the three components position H2A-H2B for release. Here, we show cryo-EM structures of Importin-9•RanGTP and of its yeast homolog Kap114, including Kap114•RanGTP, Kap114•H2A-H2B, and RanGTP•Kap114•H2A-H2B, to explain how the conserved Kap114 binds H2A-H2B and RanGTP simultaneously and how the GTPase primes histone transfer to the nucleosome. In the ternary complex, RanGTP binds to the N-terminal repeats of Kap114 in the same manner as in the Kap114/Importin-9•RanGTP complex, and H2A-H2B binds via its acidic patch to the Kap114 C-terminal repeats much like in the Kap114/Importin-9•H2A-H2B complex. Ran binds to a different conformation of Kap114 in the ternary RanGTP•Kap114•H2A-H2B complex. Here, Kap114 no longer contacts the H2A-H2B surface proximal to the H2A docking domain that drives nucleosome assembly, positioning it for transfer to the assembling nucleosome or to dedicated H2A-H2B chaperones in the nucleus. 

Water harvesting from air is desired for decentralized water supply wherever water is needed. When water vapor is condensed as droplets on a surface the unremoved droplets act as thermal barriers. A surface that can provide continual droplet-free areas for nucleation is favorable for condensation water harvesting. Here, we report a flow-separation condensation mode on a hydrophilic reentrant slippery liquid-infused porous surface (SLIPS) that rapidly removes droplets with diameters above 50 μm. The slippery reentrant channels lock the liquid columns inside and transport them to the end of each channel. We demonstrate that the liquid columns can harvest the droplets on top of the hydrophilic reentrant SLIPS at a high droplet removal frequency of 130 Hz/mm 2 . The sustainable flow separation without flooding increases the water harvesting rate by 110% compared to the state-of-the-art hydrophilic flat SLIPS. Such a flow-separation condensation approach paves a way for water harvesting.