Abstract Garnet oxide is one of the most promising solid electrolytes for solid-state lithium metal batteries. However, the traditional interface modification layers cannot completely block electron migrating from the current collector to the interior of the solid-state electrolyte, which promotes the penetration of lithium dendrites. In this work, a highly electron-blocking interlayer composed of potassium fluoride (KF) is deposited on garnet oxide Li 6.4 La 3 Zr 1.4 Ta 0.6 O 12 (LLZTO). After reacting with melted lithium metal, KF in-situ transforms to KF/LiF interlayer, which can block the electron leakage and inhibit lithium dendrite growth. The Li symmetric cells using the interlayer show a long cycle life of ~3000 hours at 0.2 mA cm −2 and over 350 hours at 0.5 mA cm −2 respectively. Moreover, an ionic liquid of LiTFSI in C 4 mim-TFSI is screened to wet the LLZTO|LiNi 0.8 Co 0.1 Mn 0.1 O 2 (NCM) positive electrode interfaces. The Li|KF-LLZTO | NCM cells present a specific capacity of 109.3 mAh g −1 , long lifespan of 3500 cycles and capacity retention of 72.5% at 25 °C and 2 C (380 mA g −1 ) with an average coulombic efficiency of 99.99%. This work provides a simple and integrated strategy on high-performance quasi-solid-state lithium metal batteries.
Temperature sensing is crucial for homeotherms, including human beings, to maintain a stable body core temperature and respond to the ambient environment. A group of exquisitely temperature-sensitive transient receptor potential channels, termed thermoTRPs, serve as cellular temperature sensors. How thermoTRPs convert thermal energy (heat) into protein conformational changes leading to channel opening remains unknown. Here we demonstrate that the pathway for temperature-dependent activation is distinct from those for ligand- and voltage-dependent activation and involves the pore turret. We found that mutant channels with an artificial pore turret sequence lose temperature sensitivity but maintain normal ligand responses. Using site-directed fluorescence recordings we observed that temperature change induces a significant rearrangement of TRPV1 pore turret that is coupled to channel opening. This movement is specifically associated to temperature-dependent activation and is not observed during ligand- and voltage-dependent channel activation. These observations suggest that the turret is part of the temperature-sensing apparatus in thermoTRP channels, and its conformational change may give rise to the large entropy that defines high temperature sensitivity.
The newly discovered Ca 2+ -activated Cl − channel (CaCC), Anoctamin 1 (Ano1 or TMEM16A), has been implicated in vital physiological functions including epithelial fluid secretion, gut motility, and smooth muscle tone. Overexpression of Ano1 in HEK cells or Xenopus oocytes is sufficient to generate Ca 2+ -activated Cl − currents, but the details of channel composition and the regulatory factors that control channel biology are incompletely understood. We used a highly sensitive quantitative SILAC proteomics approach to obtain insights into stoichiometric protein networks associated with the Ano1 channel. These studies provide a comprehensive footprint of putative Ano1 regulatory networks. We find that Ano1 associates with the signaling/scaffolding proteins ezrin, radixin, moesin, and RhoA, which link the plasma membrane to the cytoskeleton with very high stoichiometry. Ano1, ezrin, and moesin/radixin colocalize apically in salivary gland epithelial cells, and overexpression of moesin and Ano1 in HEK cells alters the subcellular localization of both proteins. Moreover, interfering RNA for moesin modifies Ano1 current without affecting its surface expression level. Another network associated with Ano1 includes the SNARE and SM proteins VAMP3, syntaxins 2 and -4, and syntaxin-binding proteins munc18b and munc18c, which are integral to translocation of vesicles to the plasma membrane. A number of other regulatory proteins, including GTPases, Ca 2+ -binding proteins, kinases, and lipid-interacting proteins are enriched in the Ano1 complex. These data provide stoichiometrically prioritized information about mechanisms regulating Ano1 function and trafficking to polarized domains of the plasma membrane.
Elucidating protective immunity against HCV is important for the development of a preventative vaccine. We hypothesize that spontaneous resolution of acute HCV infection offers clue to protective immune responses, and that DAA therapy affects the quality and quantity of HCV-specific T cell responses. To test these hypotheses, we performed T cell epitope mapping in 111 HCV-infected individuals including 61 chronically HCV-1b (CHC-1b) infected, 24 chronically HCV-2a (CHC-2a) infected and 26 spontaneously recovered (SPR) patients with 376 overlapping peptides covering the entire HCV polyprotein. Selected T cell epitopes were then used to evaluate T cell responses in another 22 chronically HCV-1b infected patients on DAA therapy. Results showed that SPR had better HCV-specific T cell responses than CHC, as manifested by higher response rate, greater magnitude and broader epitope coverage. In addition, SPR recognized novel epitopes in Core, E1, E2, NS4B, NS5A regions that were not present in the CHC. Furthermore, during the first 24 weeks of DAA therapy, there was no functional immune reconstitution of HCV-specific T cells. These results indicate that T cell responses may be a correlate of protection. Therefore, effective preventative vaccines should elicit a robust T cell response. Although various DAA regimens efficiently cleared viruses from the blood of HCV-infected patients, there was no contemporaneous early T cell immune reconstitution, suggesting that early treatment is needed for preserving the functions of HCV-specific T cells.
Numerous studies of thermosensitive transient receptor potential (thermoTRP) channels have focused on the outer pore that contains sites critical for the channel's sensitivity to temperature, acidification, spider toxin, and other gating modulators (Fig. 1). Two segments of each subunit contribute to the outer pore structure: one is between S5 and the pore helix, the other is between the selectivity filter and S6. For the convenience of discussion, we call them the large turret and the small turret, respectively. From the available structural information of tetrameric channels, it is expected that the two turrets interact extensively. Indeed, the sites affecting gating spread across the outer pore landscape. Of particular interests are a number of sites that when mutated, lead to permanent opening or closing of the temperature-activation gate (1–3).
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