Glioblastoma multiforme (GBM) is the most prevalent form of malignant brain tumor. Amlexanox, a novel compound, has been shown to have anti-cancer potential. In this study, the anti-tumoral effects and the underlying mechanisms of amlexanox were investigated. Amlexanox significantly suppressed proliferation and invasion and induced apoptosis in glioblastoma cells. Furthermore, we found that amlexanox altered the protein expression of the Hippo pathway by downregulating IKBKE. Our data indicates that IKBKE directly targets LATS1/2 and induces degradation of LATS1/2, thereby inhibiting the activity of the Hippo pathway. In vivo results further confirmed the tumor inhibitory effect of amlexanox via the downregulation of IKBKE, and amlexanox induced no apparent toxicity. Collectively, our studies suggest that amlexanox is a promising therapeutic agent for the treatment of GBM.

Resistance to antiestrogens is one of the major challenges in breast cancer treatment. Although phosphorylation of estrogen receptor α (ERα) is an important factor in endocrine resistance, the contributions of specific kinases in endocrine resistance are still not fully understood. Here, we report that an important innate immune response kinase, the IκB kinase-related TANK-binding kinase 1 (TBK1), is a crucial determinant of resistance to tamoxifen therapies. We show that TBK1 increases ERα transcriptional activity through phosphorylation modification of ERα at the Ser-305 site. Ectopic TBK1 expression impairs the responsiveness of breast cancer cells to tamoxifen. By studying the specimens from patients with breast cancer, we find a strong positive correlation of TBK1 with ERα, ERα Ser-305, and cyclin D1. Notably, patients with tumors highly expressing TBK1 respond poorly to tamoxifen treatment and show high potential for relapse. Therefore, our findings suggest that TBK1 contributes to tamoxifen resistance in breast cancer via phosphorylation modification of ERα.T ANK-binding kinase 1 (TBK1) and IκB kinase e (IKKe) are two IKK-related serine/threonine kinases that display 64% sequence identity and trigger the antiviral response of interferons (IFN) through NF-κB activation and interferon regulatory transcription factor (IRF) 3/7 phosphorylation (1-3). In addition to the proposed roles of IKK-related kinases in controlling transcription factors NF-κB and IRF, the involvement of TBK1 and IKKe in AKT-induced oncogenic transformation has been demonstrated in a recent study (4). TBK1 is identified as a Raslike (Ral) B effector in the Ral guanine nucleotide exchange factor pathway that is required for Ras-induced transformation (5). IKKe acts downstream of the PI3K-AKT pathway and cooperates with activated MEK to promote cellular transformation (6). IKKe has also been identified recently as a breast cancer oncogene that is frequently amplified or overexpressed in human breast cancer, and the phosphorylation of ERα by IKKe contributes to tamoxifen resistance in breast cancer (7-9). Interestingly, TBK1 is also highly expressed in breast cancer (10), and knocking down TBK1 diminishes the viability of MCF-7 cells (9). However, the exact role of TBK1 in breast cancer remains unclear.Estrogen receptor α (ERα) is a nuclear receptor that exerts a profound influence on the initiation and progression of breast cancer by regulating cell transformation, proliferation, and metastasis (11-13). For ERα-positive patients with breast cancer, targeting the ER signaling pathway with tamoxifen, a selective ER modulator, is efficacious in both prevention and treatment of breast cancer (14). Unfortunately, a substantial proportion of patients are intrinsically resistant to this therapy, and a significant number of patients with advanced disease eventually develop acquired resistance to the treatment (15-18). ERα is a key determinant of breast cancer susceptibility to endocrine therapy. Recent studies demonstrate that ERα phosphorylation ...

The transwell chamber migration assay and CCD digital camera imaging techniques were used to investigate the relationship between regulatory volume decrease (RVD) and cell migration in nasopharyngeal carcinoma cells (CNE-2Z cells). Both migrated and non-migrated CNE-2Z cells, when swollen by 47% hypotonic solution, exhibited RVD which was inhibited by extracellular application of chloride channel blockers adenosine 5'-triphosphate (ATP), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and tamoxifen. However, RVD rate in migrated CNE-2Z cells was bigger than that of non-migrated cells and the sensitivity of migrated cells to NPPB and tamoxifen was higher than that of nonmigrated cells. ATP, NPPB and tamoxifen also inhibited migration of CNE-2Z cells. The inhibition of migration was positively correlated to the blockage of RVD, with a correlation coefficient (r) = 0.99, suggesting a functional relationship between RVD and cell migration. We conclude that RVD is involved in cell migration and RVD may play an important role in migratory process in CNE-2Z cells.

The use of single-crystal substrates as templates for the epitaxial growth of single-crystal overlayers has been a primary principle of materials epitaxy for more than 70 years. Here we report our finding that, though counterintuitive, single-crystal 2D materials can be epitaxially grown on twinned crystals. By establishing a geometric principle to describe 2D materials alignment on high-index surfaces, we show that 2D material islands grown on the two sides of a twin boundary can be well aligned. To validate this prediction, wafer-scale Cu foils with abundant twin boundaries were synthesized, and on the surfaces of these polycrystalline Cu foils, we have successfully grown wafer-scale single-crystal graphene and hexagonal boron nitride films. In addition, to greatly increasing the availability of large area high-quality 2D single crystals, our discovery also extends the fundamental understanding of materials epitaxy.

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Background Surgical site infection (SSI) is a common complication after abdominal surgery. The effectiveness of wound edge protectors in reducing infection of the surgical sites is still unclear. The purpose of this study was to determine the clinical effectiveness of a wound edge protector (WEP) in reducing SSI rates after abdominal surgery. Methods PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched to obtain relevant articles published up to September 2021. Publications were retrieved if they contain primary data on the use of WEPs in reducing SSI compared with standard care in patients undergoing abdominal surgery. Subgroup analyses were performed for different WEP types, surgical sites, and levels of contamination. The outcome of interest was a clinically defined SSI. Qualitative variables were pooled using risk ratios (RRs). Results Twenty-two eligible randomized clinical trials involving 4492 patients were included in this meta-analysis. WEP was associated with the reduced incidence of overall SSI (RR = 0.66; 95 per cent c.i. 0.53 to 0.83; P = 0.0003), and superficial SSI (RR = 0.59; 95 per cent c.i. 0.38 to 0.91; P = 0.02). In addition, WEP also successfully reduced the risk of SSI in clean-contaminated wounds (RR = 0.61; 95 per cent c.i. 0.40 to 0.93; P = 0.02) as well as in contaminated wounds (RR = 0.47; 95 per cent c.i. 0.33 to 0.67; P < 0.0001); however, WEP did not reduce SSI incidence in colorectal surgery (RR = 0.68; 95 per cent c.i. 0.46 to 1.01; P = 0.05). Conclusion This study suggests that WEP was efficient in reducing superficial SSI. Both double-ringed and single-ringed devices were efficient in reducing SSI. WEP was effective in reducing SSI incidence in clean-contaminated and contaminated surgery; however, its use does not reduce the SSI rate in colorectal surgery.

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Removal of the native surface oxide from steel is an important initial step during vacuum brazing. Trace and alloying elements in steel, such as Mn, Si, and Ni, can diffuse to the surface and influence the deoxidation process. The detailed surface chemical composition and grain morphology of the common stainless‐steel grade 316L is imaged and spectroscopically analyzed at several stages of in‐vacuum annealing from room temperature up to 850°C. Measurements are performed using synchrotron‐based X‐ray photoemission and low‐energy electron microscopy (XPEEM/LEEM). The initial native Cr surface oxide is amorphous and unaffected by the underlying Fe grain morphology. After annealing to ~700°C, the grain morphology is seen at the surface, persisting also after the complete oxygen removal at 850°C. The surface concentration of first Mn and then Si increases significantly when annealing to 500°C and 700°C, respectively, while Ni and Cr concentrations do not change. Mn and Si are not located only in grain boundaries or clusters but are distributed across over the surface. Both Mn and Si appear as oxides, while Cr oxide becomes metallic Cr. Annealing from 500°C up to 850°C leads to the removal of first the Mn and then Si oxides from the surface, while Cr and Fe are completely reduced to metals. Deoxidation of Cr occurs faster at the grain boundaries, and the final Cr metal surface content varies between the grains. The findings are summarized in a general qualitative model, relevant for austenite steels.