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Background Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer worldwide and is one of the most lethal malignancies. Cisplatin (DDP) is a key drug for ESCC treatment, but the presence of chemotherapy resistance limits the use of DDP. To enhance chemosensitivity to DDP is important for ESCC treatment. Methods qRT-PCR and Western blotting detected mRNA and protein expression in ESCC tissues and cells. Luciferase reporter assay assessed the interaction between miR-145 and AKT3. Cell cycle, apoptosis and proliferation were investigated with flow cytometry and MTT assay, respectively. Nude mice xenograft model was established, and immunohistochemistry (IHC) and TUNEL assay were conducted to detect Ki-67 level and apoptosis in xenograft tumor. Results Down-regulated miR-145 and up-regulated AKT3 were observed in ESCC tissues and cells. Luciferase reporter assay revealed that miR-145 negatively regulated AKT3 through binding to its 3′-UTR. Overexpression of miR-145 or knockdown of AKT3 promoted DDP-induced cell cycle arrest and apoptosis, as well as reduced IC50 of DDP treatment, which was reversed by AKT3 overexpression. The expression level of MRP1, P-gp, CyclinD1, c-Myc and anti-apoptotic protein Bcl-2 were down-regulated, while pro-apoptotic protein Bax was up-regulated by miR-145. Furthermore, overexpression of miR-145 enhanced the DDP-induced tumor growth suppression in vivo. Conclusion miR-145 increased the sensitivity of ESCC to DDP, and facilitated DDP-induced apoptosis, cycle arrest by directly inhibiting PI3K/AKT signaling pathway to decrease multidrug resistance-associated proteins MRP1 and P-gp expression. Improving the efficacy of DDP by boosting the miR-145 level provides a new strategy for treatment of ESCC.

However, the further development of LIBs is restricted by the limited energy density, especially given the emerging large-scale energy storage applications. [2] Lithium metal is a competitive anode candidate with the merits of high theoretical capacity (3860 mAh g −1 ) and very low reduction potential (−3.04 V vs a standard hydrogen electrode). [3] Nonetheless, the problem of lithium dendrites and the stability of the electrolyte-electrode interphase still hinder its commercialization. [4] Furthermore, conventional carbonate electrolytes are flammable and can induce lithium dendrites, resulting in the production of "dead Li," which reduces the battery performance and raises safety concerns. [5] To address the severe dendrite issues in lithium metal batteries (LMBs), the formula design of the electrolyte has been proven to be an effective strategy. [6] As an additive, Lithium nitrate (LiNO 3 ) is generally recognized as an enhancer that forms robust solid electrolyte interphase (SEI) layers. [7] The NO 3 − derived reduction products, such as Li x N and LiN x O y , are good Li + conductors, thus accelerating the plating/ stripping behavior of Li + . [8] In addition, LiNO 3 binds to solvents or active substances in the electrolyte to strengthen the SEI layers and inhibit dendritic growth. [9] However, the strong interaction between Li + and NO 3 − cannot be broken in the conventional carbonate electrolyte, resulting in the extremely low solubility of LiNO 3 and hindering its application. [10] Although the ether electrolyte can dissolve a certain amount of LiNO 3 , its low operating voltage makes it difficult to meet the requirement of the LMB. Hence, it is essential to develop a safe and stable electrolyte with high LiNO 3 solubility to achieve better LMB. To date, various strategies have been reported to promote LiNO 3 dissolution in carbonate electrolytes such as using co-solvents, [11] slow release, [12] polymer-mediation, [13] and introducing solvent promoters. [14] However, these methods are characterized by complex processes and high costs. Therefore, there is an urgent need for a method that can facilitate LiNO 3 dissolution. Deep eutectic solvents (DESs), eutectic liquid mixtures of two or more solids formed by strong intermolecular forces, are new green solvents that have been widely utilized in extraction, organic synthesis, and electrochemistry. [15] DESs exist as liquids over a wide range of temperatures and offer excellent thermal stability. Moreover, Lithium nitrate is widely used as an additive in electrolytes to regulate the solid electrolyte interphase (SEI). However, the application of LiNO 3 in lithium metal batteries (LMBs) is limited by its extremely low solubility in conventional carbonate-based electrolytes. In this study, a non-flammable deep eutectic solvent (DES) with lithium bis(trifluoromethanesulfonyl)imide and N-methylacetamide (NMAC) as the main components is chosen as the LMB electrolyte. Using theoretical calculations and experiments, the strong interaction between NMAC and LiNO ...

Garnet-type Li7La3Zr2O12 (LLZO) has been widely used as a filler in composite solid electrolytes (CSEs) to achieve high-performance solid-state batteries (SSBs). Unfortunately, moisture-sensitive LLZO suffers from surface Li2CO3 passivation when being exposed to an ambient atmosphere. The insulated Li2CO3 layer is thought to reduce the Li+ transportability of CSEs. However, further studies are still needed to find out the underlying mechanism, which helps to guide future filler modification and electrolyte design. Herein, the role of the Li2CO3 layer in CSEs is elucidated from different perspectives. The passivate Li2CO3 layer is verified to prohibit the formation of the high conductive interlayer, change the Li+ transport pathway, and decrease the carrier concentration in CSEs. Also, the Li2CO3 layer would reduce the electropositivity of Li6.4La3Zr1.4Ta0.6O12 (LLZTO) particles, which therefore weakens the anchoring effect toward bis­(trifluoromethanesulfonyl)­imide (TFSI)−. Accordingly, without Li2CO3, the electrolyte of polyethylene oxide/LiTFSI/IL (ionic liquid) with LLZTO-AT (PLILA) displays 2 times higher ionic conductivity and an improved Li+ transference number of 0.49. Additionally, an excellent cycling performance is presented in Li symmetric cells and full cells with PLLA. This work provides a novel perspective for future research on lithium-ion transport mechanisms and inspires designing better-performance SSBs.