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Due to its extensive application, the safety issue of lithium-ion battery has received increasing attention. For crashworthiness design of battery in electric vehicles, it is of great importance to investigate the response of the battery under mechanical loading and understand the mechanism of internal short circuit. Quasi-static and intermediate strain rate uniaxial tension tests were conducted on the electrodes and the separators. The high speed camera and DIC (digital image correlation) method were adopted to measure the strain while a self-design load cell was used to measure force in dynamic test. Either loading velocity or loading direction was varied in different tests. The upper limit of the test strain rate achieved 66 /sec. All the component materials showed strain rate dependency and separators demonstrated noticeable anisotropy. Quasi-static penetration tests were conducted on two different types of pouch cell using steel and plastic punch heads. For both Type A pouch cell and Type B pouch cell, during penetration process using plastic punch head, no significant voltage drop or temperature rise was observed. During penetration process using steel punch head, only Type A pouch cell produced short circuit. When the punch head was removed, the voltage of the cells could recover to certain level. From post mortem examination, it was found that for a single pouch cell, all the electrodes presented the same fracture mode that the stacked anode and cathode formed several fragments in the penetration path, while the separators in between only formed a central crack when the punch head went through. Since the separators had a larger elongation ratio than the electrodes, the extended separators around the rupture location could block the direct and constant contact between anode and cathode, electrodes and steel punch, which explained why no massive internal short circuit was initiated. The drop tower was used to conduct dynamic penetration test. The results indicated that under dynamic loading, internal short circuit was more likely to be triggered which can be explained by the strain rate effect of the separators. This study highlighted the importance of the separator to the safety performance of pouch cells.

Tumor heterogeneity limits the precision treatment of targeted drugs. It is important to find new tumor targets. JWA, also known as ADP ribosylation factor-like GTPase 6 interacting protein 5 (ARL6IP5, GenBank: AF070523, 1998), is a microtubule-associated protein and an environmental response gene. Substantial evidence shows that JWA is low expressed in a variety of malignancies and is correlated with overall survival. As a tumor suppressor, JWA inhibits tumor progression by suppressing multiple oncogenes or activating tumor suppressor genes. Low levels of JWA expression in tumors have been reported to be associated with multiple aspects of cancer progression, including angiogenesis, proliferation, apoptosis, metastasis, and chemotherapy resistance. In this review, we will discuss the structure and biological functions of JWA in tumors, examine the potential therapeutic strategies for targeting JWA and explore the directions for future investigation.

Lung adenocarcinoma (LUAD) is the most common lung cancer, with high mortality. As a tumor-suppressor gene, JWA plays an important role in blocking pan-tumor progression. JAC4, a small molecular-compound agonist, transcriptionally activates JWA expression both in vivo and in vitro. However, the direct target and the anticancer mechanism of JAC4 in LUAD have not been elucidated. Public transcriptome and proteome data sets were used to analyze the relationship between JWA expression and patient survival in LUAD. The anticancer activities of JAC4 were determined through in vitro and in vivo assays. The molecular mechanism of JAC4 was assessed by Western blot, quantitative real-time PCR (qRT-PCR), immunofluorescence (IF), ubiquitination assay, co-immunoprecipitation, and mass spectrometry (MS). Cellular thermal shift and molecule-docking assays were used for confirmation of the interactions between JAC4/CTBP1 and AMPK/NEDD4L. JWA was downregulated in LUAD tissues. Higher expression of JWA was associated with a better prognosis of LUAD. JAC4 inhibited LUAD cell proliferation and migration in both in-vitro and in-vivo models. Mechanistically, JAC4 increased the stability of NEDD4L through AMPK-mediated phosphorylation at Thr367. The WW domain of NEDD4L, an E3 ubiquitin ligase, interacted with EGFR, thus promoting ubiquitination at K716 and the subsequent degradation of EGFR. Importantly, the combination of JAC4 and AZD9191 synergistically inhibited the growth and metastasis of EGFR-mutant lung cancer in both subcutaneous and orthotopic NSCLC xenografts. Furthermore, direct binding of JAC4 to CTBP1 blocked nuclear translocation of CTBP1 and then removed its transcriptional suppression on the JWA gene. The small-molecule JWA agonist JAC4 plays a therapeutic role in EGFR-driven LUAD growth and metastasis through the CTBP1-mediated JWA/AMPK/NEDD4L/EGFR axis.

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