We have successfully controlled the shape of gold nanocrystals through a simple and low‐cost hydrothermal method based on a modified polyol process. Well‐defined gold nanocrystals of icosahedral shape were synthesized in high yields by the rapid reduction of gold precursors with ethylene glycol (EG) in the presence of poly(vinyl pyrrolidone) (PVP) under hydrothermal conditions for 1 h. Truncated icosahedra (football‐shaped) have been prepared for the first time by prolonging the reaction time to 4 h. Both nanocrystal shapes were obtained quantitatively. Addition of citric acid inhibits the shape‐change process (from icosahedron to truncated icosahedron) by blocking oxidative etching, while addition of Fe(III) facilitates the shape‐change process by enhancing oxidative etching. We propose that growth of truncated icosahedra can be induced and maintained through interplay of the following processes: generation of multiple twinned seeds, shape‐ and size‐focusing by Ostwald ripening, and oxidative etching and preferential growth on the {100} face.
BackgroundUncoordinated 51-like kinase 1 (ULK1) plays a vital role in autophagy. ULK1 dysregulation has recently been found in several human cancers.MethodsmRNA expression levels of ULK1 and clinical information were analysed from The Cancer Genome Atlas data. ULK1 expression levels were verified in 36 paired fresh ccRCC tissue specimens by western blot analysis. Expression of ULK1 was knockdown by shRNA lentivirus. ULK1 activity was inhibited by SBI-0206965. The effect of inhibition of ULK1 was measured by detecting the apoptotic rate, autophagy, and the ratio of ROS and NADPH. The efficacy of SBI-0206965 in vivo was assessed by the murine xenograft model.FindingsULK1 mRNA expression was significantly upregulated in clear cell renal cell carcinoma (ccRCC) and overexpression of ULK1 correlated with poor outcomes. We found that ULK1 was highly expressed in 66.7% of ccRCC tumours (p < 0·05). Knockdown of ULK1 and selective inhibition of ULK1 by SBI-0206965 induced cell apoptosis in ccRCC cells. We demonstrated that SBI-0206965 triggered apoptosis by preventing autophagy and pentose phosphate pathway (PPP) flux. Furthermore, blocking the kinase activity of ULK1 with SBI-0206965 resulted in a level of anticancer effect in vivo.InterpretationTaken together, our results suggested that ULK1 was upregulated in ccRCC tumours and may be a potential therapeutic target. Therefore, SBI-0206965 should be further considered as an anti-ccRCC agent.FundThis work was supported in part by The (No. 81570748) and (No. 2018J01345, 2017XQ1194).
Insulin-like growth factor (IGF) signaling is involved in oral squamous cell carcinoma (OSCC), but IGF-1 receptor (IGF-1R)-mediated intricate regulatory networks among molecular interactions and signalling path ways in OSCC remain unclear. Here, we found that overexpression of IGF-1R and insulin receptor substrate-2 (IRS-2) was negatively associated with histological differentiation. IGF signaling stimulated OSCC cell growth. Conversely, overexpression of let-7b inhibited proliferation and colony formation and triggered S/G2 cell cycle arrest by targeting IGF-1R and IRS-2 through the Akt pathway. Also, the inverse relationship between expression of let-7b and IGF-1R/IRS-2 was confirmed in OSCC tumor xenografts and clinical specimens. Furthermore, by activating ERK1/2, IGF-1R transcriptionally upregulated IRS-2. Our results indicate that let-7b/IGF-1R-mediated crosstalk between IRS-2/Akt and MAPK is involved in OSCC and is a potential therapeutic target for therapy.
At present, the structure−activity relationships of soy protein isolate are still not well understood. In this paper, the relationship between molecular flexibility and emulsifying properties of soy protein isolate and soy protein isolate−glucose conjugates were investigated. The Maillard reaction was carried out at different temperature conditions (50 °C, 60 °C, 70 °C, 80 °C, and 90 °C) under a specific wet condition. Meanwhile, structural properties including surface hydrophobicity (H 0 ), molecular flexibility and secondary, tertiary, quaternary structures, and the free sulfhydryl group (−SH) content were measured. The results showed that there was a good correlation between molecular flexibility and emulsifying properties, and the correlation coefficients was 0.920 (P < 0.01) for emulsifying activity and 0.952 (P < 0.01) for emulsion stability. Compared with soy protein isolate, the H 0 of samples at different temperatures first increased and then decreased reaching a maximum at 70 °C, a red shift occurred during the whole given reaction conditions shown by the intrinsic fluorescence spectrum, and the free sulfhydryl content also displayed a marked increase (P < 0.05). At the same time, the particle size gradually became smaller as the degree of grafting increased. The contents of β-turn and random coil increased at the cost of α-helix and β-sheet contents, as evidenced by Fourier transform infrared results. The findings could provide a deep insight into the structure−function relationship of soy protein isolate−glucose conjugates, thus providing theoretical guidance for further research of soy proteins.
Background: Clear cell renal cell carcinoma (ccRCC) is a malignancy characterized by metabolic reprogramming. ABAT and ALDH6A1 are metabolic enzymes. In this study, we aim to investigate the associations of ABAT and ALDH6A1 with the malignancy of ccRCC cells. Methods: The gene expression levels of ABAT and ALDH6A1 in ccRCC were analyzed from gene expression microarray datasets and RNA sequencing data. Clinical information was analyzed from The Cancer Genome Atlas (TCGA) data. The distributions of ABAT and ALDH6A1 in ccRCC clinical tissues were screened by reverse transcription-quantitative polymerase chain reaction (RT-QPCR) and immunohistochemical assays. The effect of overexpression of ABAT or ALDH6A1 was measured by detecting the cell viability, migration ability, and the ratio of lactate and nicotinamide adenine dinucleotide phosphate (NADPH). Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were carried out to investigate the transcript regulation of HNF4A in ABAT and ALDH6A1. Results: Remarkable downregulated ABAT and ALDH6A1 expression levels were observed in ccRCC patients and low expression of ABAT and ALDH6A1 was correlated with poor survival. Overexpression of ABAT or ALDH6A1 significantly attenuated cell proliferation and migration, and impaired lactate production. In ABAT increased ccRCC cells, the ratio of NADPH/NADP+ was reduced. Finally, we demonstrated that ABAT and ALDH6A1 were directly regulated by a tumor suppressor, HNF4A. Conclusions: These observations identified HNF4A-regulated low-expressed ABAT and ALDH6A1 as promising diagnostic and prognostic biomarkers for ccRCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.