RP11-874 J12.4 promotes erlotinib resistance in non-small cell lung cancer via increasing AXL expression.

EGFR tyrosine kinase inhibitor (TKI) resistance is a major challenge for EGFR-mutant non-small cell lung cancer (NSCLC) treatment. Our previous work revealed that overexpression of AXL promoted EGFR-TKI resistance through epithelial-mesenchymal transition (EMT) in a subset of NSCLC patients. Compared with erlotinib resistant and sensitive cells, RP11-874 J12.4 was upregulated in erlotinib-resistant NSCLC cells (HCC827-ER3). Interestingly, the expression of RP11-874 J12.4 positively correlated with AXL. Besides, RP11-874 J12.4 promotes NSCLC cell proliferation and metastasis in vitro. Mechanistically, RP11-874 J12.4 promoted AXL expression through sponge with miR-34a-5p, which was reported to inhibit the translation of AXL mRNA. Meanwhile, the expression of RP11-874 J12.4 in lung cancer tumors were higher than the adjacent tissue, and those patients with high expression of RP11-874 J12.4 showed a poor prognosis in clinical. High expression of RP11-874 J12.4 might be a biomarker for NSCLC patients with erlotinib resistance. These findings reveal a novel insight into the mechanism of erlotinib resistance in NSCLC, and it might be a promising target for the diagnosis and treatment of NSCLC.

Realistic fault detection of li-ion battery via dynamical deep learning.

Accurate evaluation of Li-ion battery (LiB) safety conditions can reduce unexpected cell failures, facilitate battery deployment, and promote low-carbon economies. Despite the recent progress in artificial intelligence, anomaly detection methods are not customized for or validated in realistic battery settings due to the complex failure mechanisms and the lack of real-world testing frameworks with large-scale datasets. Here, we develop a realistic deep-learning framework for electric vehicle (EV) LiB anomaly detection. It features a dynamical autoencoder tailored for dynamical systems and configured by social and financial factors. We test our detection algorithm on released datasets comprising over 690,000 LiB charging snippets from 347 EVs. Our model overcomes the limitations of state-of-the-art fault detection models, including deep learning ones. Moreover, it reduces the expected direct EV battery fault and inspection costs. Our work highlights the potential of deep learning in improving LiB safety and the significance of social and financial information in designing deep learning models.

Cytoplasmic Clusterin Suppresses Lung Cancer Metastasis by Inhibiting the ROCK1-ERK Axis.

Clusterin (CLU) is a heterodimeric glycoprotein that has been detected in diverse human tissues and implicated in many cellular processes. Accumulating evidence indicates that the expression of secreted CLU correlates with the progression of cancers. However, the molecular mechanisms underlying its tumor-suppressive roles are incompletely uncovered. In this study, we demonstrate that precursor CLU is widely downregulated in lung cancer tissue, in which secretory CLU proteins are slightly decreased. Impressively, overexpressing CLU potently inhibits the migration, invasion and metastasis of lung cancer cells, whereas silencing CLU promotes this behavior; however, it appears that secretory CLU fails to exert similar anti-metastatic effects. Interestingly, the cytoplasmic precursor CLU binds ROCK1 to abrogate the interaction between ROCK1 and ERK and impair ERK activity, leading to the suppression of lung cancer invasiveness. Meanwhile, the expression of CLU was remarkably diminished in lung cancer bone metastasis loci when compared with subcutaneous tumors in the mouse model and hardly detected in the bone metastasis loci of lung cancer patients when compared with the primary. These findings reveal a novel insight into the function and regulation of cytoplasmic CLU in lung cancer, which might be a potential target for the diagnosis and treatment of metastatic lung cancer.

Confined Lithium Deposition Triggered by an Integrated Gradient Scaffold for a Lithium-Metal Anode.

Constructing a composite lithium anode with a rational structure has been considered as an effective approach to regulate and relieve the tough problems of a sparkling Li anode. However, the potential short circuits risk that Li deposition at the surface of the framework has not yet been resolved. Here, we present a simple regulating-deposition strategy to guide the preferentially bottom-up deposition/growth of Li. The triple-gradient structure of modified porous copper with electrical passivation (top) and chemical activation (bottom) shows significant improvements in the morphological stability and electrochemical performance. Meanwhile, the in situ generation of Li2Se can as an advanced artificial SEI layer be devoted to homogeneous Li plating/stripping. As a result, the composite anode exhibits a long-term cycling over 250 cycles with a high average CE of 98.2% at 1 mA cm-2. Furthermore, a capacity retention of 94.4% in full cells can be achieved when pairing with LiFePO4 as the cathode. These results ensure a bright direction for developing high-performance Li metal anodes.

Modifying Ti-Based Gas Diffusion Layer Passivation for Polymer Electrolyte Membrane Water Electrolysis via Electrochemical Nitridation.

A gas diffusion layer represents an important element of collector and stack components used in polymer electrolyte membrane (PEM) water electrolyzers (WE). Nowadays, titanium-based gas diffusion layers (GDLs) have high stability and are frequently employed as anode GDLs, yet reliability issues emerging from passivation have limited their practical deployment. Hence, we develop an inexpensive way of producing high conductivity and corrosion resistance of Ti-based GDLs through electrochemical nitridation. The morphology and content of the nitride phase on the surface of the Ti felt GDL are efficiently regulated by adjusting reduction potential and reaction time. According to X-ray photoelectron spectroscopy studies, the modified Ti felt is coated with ammonium ions and nitrogen-incorporated oxides, namely, TiN/TiOx, on the surface. The nitride surface shows a low interfacial contact resistance (ca. 1.0 mΩ cm2 at 140 N/cm2) and excellent corrosion resistance (0.920 µA cm-2) in the simulated PEM WE environments. The electrochemical nitridation provides an economic way to introducing N layers on the surface of the Ti-based GDL with high performance, which is very promising for efficient PEM water electrolysis.

Self-Propagating Enabling High Lithium Metal Utilization Ratio Composite Anodes for Lithium Metal Batteries.

Constructing three-dimensional (3D) structural composite lithium metal anode by molten-infusion strategy is an effective strategy to address the severe problems of Li dendritic growth and huge volume changes. However, various challenges, including uncontrollable Li loading, dense inner structure, and low Li utilization, still need to be addressed for the practical application of 3D Li anode. Herein, we propose a self-propagating method, which is realized by a synergistic effect of chemical reaction and capillarity effect on porous scaffold surface, for fabricating a flexible 3D composite Li metal anode with high Li utilization ratio and controllable low Li loading. The composite 3D anode possesses controllable low loading (8.0-24.0 mAh cm-2) and uniform grid structure, realizing a stable cycling over 600 h at a high Li metal utilization ratio over 75%. The proposed strategy for fabricating composite 3D anode could promote the practical application of Li metal batteries.

Early Lithium Plating Behavior in Confined Nanospace of 3D Lithiophilic Carbon Matrix for Stable Solid-State Lithium Metal Batteries.

Considerable efforts are devoted to relieve the critical lithium dendritic and volume change problems in the lithium metal anode. Constructing uniform Li+ distribution and lithium "host" are shown to be the most promising strategies to drive practical lithium metal anode development. Herein, a uniform Li nucleation/growth behavior in a confined nanospace is verified by constructing vertical graphene on a 3D commercial copper mesh. The difference of solid-electrolyte interphase (SEI) composition and lithium growth behavior in the confined nanospace is further demonstrated by in-depth X-ray photoelectron spectrometer (XPS) and line-scan energy dispersive X-ray spectroscopic (EDS) methods. As a result, a high Columbic efficiency of 97% beyond 250 cycles at a current density of 2 mA cm-2 and a prolonged lifespan of symmetrical cell (500 cycles at 5 mA cm-2 ) can be easily achieved. More meaningfully, the solid-state lithium metal cell paired with the composite lithium anode and LiNi0.5 Co0.2 Mn0.3 O2 (NCM) as the cathode also demonstrate reduced polarization and extended cycle. The present confined nanospace-derived hybrid anode can further promote the development of future all solid-state lithium metal batteries.

Chemical Energy Release Driven Lithiophilic Layer on 1 m2 Commercial Brass Mesh toward Highly Stable Lithium Metal Batteries.

It is imperative to explore practical methods and materials to drive the development of high energy density lithium metal batteries. The constuciton of nanostructure electrodes and surface engineering on the current collectors are the two most effective strategies to regulate the homogeneous Li plating/stripping to relieve the Li dendrites and infinite volume change problems. Based on the low stacking fault energy of the Cu-Zn alloy, we present a novel chemical energy release induced surface atom diffusion strategy, which is achieved by the negative Gibbs free energy from the surface oxidation reaction and subsequent replacement reaction under thermal treatment in air, to realize a uniform upper ZnO nanoparticles coating. Furthermore, we apply the modified brass mesh as a lithiophilic current collector to decrease the Li deposition nucleation overpotential and effectively restrain the Li dendrite growth. The modified brass current collector achieves a long-term cycling stability of 500 cycles at 2.0 mA cm-2. We have verified the effectiveness of our chemical energy release modification strategy on a 1 m2 brass mesh and other Cu alloy (Tin bronze mesh), which demonstrates its great opportunities for scalable and safe lithium metal batteries.

A Cassette Containing Thiostrepton, Gentamicin Resistance Genes, and dif sequences Is Effective in Construction of Recombinant Mycobacteria.

The genetic manipulation of Mycobacterium tuberculosis genome is limited by the availability of selection markers. Spontaneous resistance mutation rate of M. tuberculosis to the widely used kanamycin is relatively high which often leads to some false positive transformants. Due to the few available markers, we have created a cassette containing thiostrepton resistance gene (tsr) for selection in M. tuberculosis and M. bovis BCG, and gentamicin resistance gene (aacC1) for Escherichia coli and M. smegmatis mc2155, flanked with dif sequences recognized by the Xer system of mycobacteria. This cassette adds to the limited available selection markers for mycobacteria.