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Trastuzumab is the backbone of HER2-directed gastric cancer therapy, but poor patient response due to insufficient cell sensitivity and drug resistance remains a clinical challenge. Here, we report that HER2 is involved in cell mitotic promotion for tumorigenesis by hyperactivating a crucial HER2-SHCBP1-PLK1 axis that drives trastuzumab sensitivity and is targeted therapeutically. SHCBP1 is an Shc1-binding protein but is detached from scaffold protein Shc1 following HER2 activation. Released SHCBP1 responds to HER2 cascade by translocating into the nucleus following Ser273 phosphorylation, and then contributing to cell mitosis regulation through binding with PLK1 to promote the phosphorylation of the mitotic interactor MISP. Meanwhile, Shc1 is recruited to HER2 for MAPK or PI3K pathways activation. Also, clinical evidence shows that increased SHCBP1 prognosticates a poor response of patients to trastuzumab therapy. Theaflavine-3, 3’-digallate (TFBG) is identified as an inhibitor of the SHCBP1-PLK1 interaction, which is a potential trastuzumab sensitizing agent and, in combination with trastuzumab, is highly efficacious in suppressing HER2-positive gastric cancer growth. These findings suggest an aberrant mitotic HER2-SHCBP1-PLK1 axis underlies trastuzumab sensitivity and offer a new strategy to combat gastric cancer.

Heteroatom nitrogen doping is considered an effective strategy to enhance the electromagnetic wave (EMW) absorption capacity of reduced graphene oxide (RGO). Herein, nitrogen‐doped RGO aerogels (NGAs) are synthesized via hydrothermal self‐assembly followed by lyophilization processes. Results of micromorphology analysis show that the as‐prepared NGAs display unique 3D porous and netlike structure. Moreover, the effects of nitrogen doping and filler contents on EMW absorption properties of NGAs are studied. The as‐synthesized NGA with nitrogen content of 9.41 at% and a bulk density of 8.7 mg cm–3 presents the integrated optimal EMW absorption performance. Specifically, the minimum reflection loss of –56.4 dB is achieved and maximum absorption bandwidth of 6.8 GHz is reached, covering the whole Ku band. In addition, the possible EMW absorption mechanisms of obtained NGAs are proposed. Therefore, the as‐synthesized NGAs can be exploited as promising high‐efficiency and lightweight EMW absorbers.

This paper presents the experimental results of four continuous reinforced concrete slabs with three compartments under different compartment fire scenarios. The research focuses on the quantitative relationships of the compartment fire temperatures, the temperature distribution along the thickness of the slabs, the vertical and horizontal deflections, the crack patterns and failure modes of the slabs and the corners' reaction forces. The results indicate that for a continuous floor slab, the central vertical deflection of the slab in the middle compartment is considerably affected by the vertical deflections of the slab in the two edge compartments. The boundary condition, the ratio and arrangement of the top reinforcement of the continuous slab, and the fire spreading scenarios have important effects on the failure mode of the slab in different compartments. It is evident that more severe cracking happened within the slab in the middle compartment compared to the two edge compartments. For the edge compartment, the slab may fail by large deflection and the integrity failure of the slab in the middle compartment may occur. Increasing reinforcement ratio and using the continuous reinforcement are the effective methods to prevent or delay the failure of the continuous slabs with any fire spreading scenarios.