Background and Purpose In non‐small‐cell lung carcinoma (NSCLC) patients, the L858R/T790M mutation of the epithelial growth factor receptor (EGFR) is a major cause of acquired resistance to EGFR‐TKIs treatment that limits their therapeutic efficacy. Identification of drugs that can preferentially kill the NSCLC harbouring L858R/T790M mutation is therefore critical. Here, we have evaluated the effects of ursolic acid, an active component isolated from herbal sources, on erlotinib‐resistant H1975 cells that harbour the L858R/T790M mutation. Experimental Approach Gene expression omnibus (GEO) profiles analyses was applied to detect differentially expressed genes in NSCLC cells harbouring EGFR mutation. AnnexinV‐FITC/PI, TUNEL staining, MTT, wound healing, RT‐PCR, qRT‐PCR, western blots, immunostaining, dual‐luciferase reporters and ChIP‐PCR were utilized to investigate the effects of ursolic acid in vitro and in vivo. Key Results The cancer/testis antigen family 45 member A2 (CT45A2) was highly expressed in H1975 cells. Ectopic expression of CT45A2 in H1975 cells increased cell proliferation and motility in vitro. Silencing the CT45A2 expression strongly attenuated H1975 cells motility and growth. The anti‐cancer effect of ursolic acid was critically dependent on CT45A2 expression in H1975 cells. Ursolic acid suppressed CT45A2 gene transcription mediated by transcriptional factor TCF4 and β‐catenin signalling. Conclusions and Implications CT45A2 is a novel oncogene for NSCLC with an EGFR T790 mutation. Ursolic acid induced apoptosis and inhibited proliferation of H1975 cells by negatively regulating the β‐catenin/TCF4/CT45A2 signalling pathway. Therefore, ursolic acid may be a potential candidate treatment for NSCLC harbouring the EGFR‐L858R/T790M mutation.

Study designThe study design of this paper is a systematic review of literature published in the recent 10 years.ObjectiveIt is the objective of this paper to compare the clinical efficacy and safety of minimal access (MIS) spinal surgery and open spinal surgery for treating painful spine metastasis.MethodsTwo research questions below were determined through a consensus among a panel of spine experts. A systematic review of literature on spinal surgery was conducted by searching PubMed with a combination of keywords including “metastatic”, “metastasis”, “metastases”, “spinal”, and “spine”. Independent reviewers selected the articles for analysis after screening the titles, abstracts, and full texts, then extracted data and graded the quality of each paper according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Specific clinical questions were as follows:In patients with spine metastatic disease, what is the impact of different surgical approaches (MIS versus open) on pain relief and functional outcome?In patients with metastatic disease, what is the impact of different surgical approaches (MIS versus open) on local recurrence, survive rate, and complication?ResultsA total of 1,076 abstracts were identified using various keywords. 5 prospective (level II) and 12 retrospective articles (level III) were eligible for inclusion, involving a total of 979 cases of spine metastasis. There were 345 cases in 8 studies regarding the clinical evaluation of MIS spinal surgery and 634 cases in 9 studies regarding the clinical evaluation of open spinal surgery for spine metastasis.ConclusionBoth open spinal surgery and MIS seem to achieve the improvement of pain and neurological dysfunction through decompression and stabilization for patients with spine metastasis, but open surgery may involve more major complications with a trend of lower survival rates and higher recurrence rates compared to MIS.

Quantifying the nodal spreading abilities and identifying the potential influential spreaders has been one of the most engaging topics recently, which is essential and beneficial to facilitate information flow and ensure the stabilization operations of social networks. However, most of the existing algorithms just consider a fundamental quantification through combining a certain attribute of the nodes to measure the nodes’ importance. Moreover, reaching a balance between the accuracy and the simplicity of these algorithms is difficult. In order to accurately identify the potential super-spreaders, the CumulativeRank algorithm is proposed in the present study. This algorithm combines the local and global performances of nodes for measuring the nodal spreading abilities. In local performances, the proposed algorithm considers both the direct influence from the node’s neighbourhoods and the indirect influence from the nearest and the next nearest neighbours. On the other hand, in the global performances, the concept of the tenacity is introduced to assess the node’s prominent position in maintaining the network connectivity. Extensive experiments carried out with the Susceptible-Infected-Recovered (SIR) model on real-world social networks demonstrate the accuracy and stability of the proposed algorithm. Furthermore, the comparison of the proposed algorithm with the existing well-known algorithms shows that the proposed algorithm has lower time complexity and can be applicable to large-scale networks.

Plant bacterial pathogens usually cause diseases by secreting and translocating numerous virulence effectors into host cells and suppressing various host immunity pathways. It has been demonstrated that the extensive ubiquitin systems of host cells are frequently interfered with or hijacked by numerous pathogenic bacteria, through various strategies. Some type-III secretion system (T3SS) effectors of plant pathogens have been demonstrated to impersonate the F-box protein (FBP) component of the SKP1/CUL1/F-box (SCF) E3 ubiquitin system for their own benefit. Although numerous putative eukaryotic-like F-box effectors have been screened for different bacterial pathogens by bioinformatics analyses, the targets of most F-box effectors in host immune systems remain unknown. Here, we show that XopI, a putative F-box effector of African Xoo (Xanthomonas oryzae pv. oryzae) strain BAI3, strongly inhibits the host's OsNPR1-dependent resistance to Xoo. The xopI knockout mutant displays lower virulence in Oryza sativa (rice) than BAI3. Mechanistically, we identify a thioredoxin protein, OsTrxh2, as an XopI-interacting protein in rice. Although OsTrxh2 positively regulates rice immunity by catalyzing the dissociation of OsNPR1 into monomers in rice, the XopI effector serves as an F-box adapter to form an OSK1-XopI-OsTrxh2 interaction complex, and further disrupts OsNPR1-mediated resistance through proteasomal degradation of OsTrxh2. Our results indicate that XopI targets OsTrxh2 and further represses OsNPR1-dependent signaling, thereby subverting systemic acquired resistance (SAR) immunity in rice.

Ionic conductive elastomers (ICEs), thanks to their liquid-free nature, have emerged as one of the most promising candidates for conductors in soft ionotronics. Notably, most ionotronic devices need to work in ambient environments where the presence of water molecules is ubiquitous. Thus far, the longterm impact of ambient water on the performances of ICEs remains virtually unexplored. Here, we show that air-aged ICEs absorb a very low amount of environmental water (∼0.3−0.6 wt % of the ICEs), which endows ICEs with stable mechanical performance and strongly boosted conductivity. We study the underlying molecular mechanism and clarify that the scission of lithium bonds between lithium ions and elastomer chains provoked by diffusing water molecules accounts for the observed changes in ICE properties. This work provides guidance for the practical mass application of ICE-based soft ionotronics in ambient environments.

Metastatic spinal tumours are the most common type of bone metastasis. Various methods have been used to treat metastatic spinal lesions, including radiotherapy, chemotherapy, isotope therapy, bisphosphonate therapy, analgesics, and surgery. Conservative treatments such as radiotherapy and chemotherapy are not appropriate and usually are ineffective in patients with vertebral fractures and/or spinal instability. Minimally invasive surgical treatments using non-vascular interventional technology, such as percutaneous vertebroplasty (PVP), have been successfully performed in the clinical setting. PVP is a non-invasive procedure that creates small wounds and is usually associated with only minor complications. In the present study, we will review the clinical status and prospects for the use PVP combined with 125I seed implantation (PVPI) to treat spinal metastases. The scientific evidence for this treatment, including safety, efficacy, and outcome measures, as well as comparisons with other therapies, was analysed in detail. PVPI effectively alleviates pain in metastatic spinal tumour patients, and the use of interstitial 125I seed implants can enhance the clinical outcomes. In conclusion, PVPI is a safe, reliable, effective, and minimally invasive treatment. The techniques of PVP and 125I seed implantation complement each other and strengthen the treatment’s effect, presenting a new alternative treatment for spinal metastases with potentially wide application.

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