Aerobic glycolysis (the Warburg effect) facilitates tumor growth, and drugs targeting aerobic glycolysis are being developed. However, how the Warburg effect is directly regulated is largely unknown. Here we show that transcription factor SIX1 directly increases the expression of many glycolytic genes, promoting the Warburg effect and tumor growth in vitro and in vivo. SIX1 regulates glycolysis through HBO1 and AIB1 histone acetyltransferases. Cancer-related SIX1 mutation increases its ability to promote aerobic glycolysis and tumor growth. SIX1 glycolytic function is directly repressed by microRNA-548a-3p, which is downregulated, inversely correlates with SIX1, and is a good predictor of prognosis in breast cancer patients. Thus, the microRNA-548a-3p/SIX1 axis strongly links aerobic glycolysis to carcinogenesis and may become a promising cancer therapeutic target.
Background:Tumoural infiltration of T lymphocytes is determined by local patterns of specific chemokine expression. In this report, we examined the roles of CCL4 and CCL20 in the accumulation of CD8+ cytotoxic T lymphocytes (CTLs) and regulatory T (Treg) lymphocytes in oesophageal squamous cell carcinoma (ESCC), and determined the correlations between chemokine expressions and ESCC patients' survival.Methods:Reverse transcriptase–PCR and immunohistochemistry (IHC) staining were performed to examine the expressions of interested genes. Flow cytometry was adopted to check the expressions of CCL4- and CCL6-specific receptors, CCR5 and CCR6, on CTLs and Treg cells. In addition, transwell assay was carried on.Results:The CCL4 expression was significantly correlated with the expression of CTL markers (CD8 and Granzyme B), whereas CCL20 was positively correlated with Treg markers (FoxP3 and IL-10). Consistently, CCR5 was found to be mainly expressed on CD8+ T lymphocytes, while CCR6 showed prevalence on Treg lymphocytes and the frequencies of CCR5+CD8+ CTLs and CCR6+ Treg cells were higher in TIL compared with PBMC. Respectively, CCL4 and CCL20 recruited CD8+ and regulatory T cells in vitro. Importantly, high levels of CCL4 in the lesions of ESCC patients predicted prolonged survival. Furthermore, CCL4high/CCL20low group demonstrated better overall survival, whereas CCL4low/CCL20low and CCL4low/CCL20high groups showed the worst overall survival.Conclusions:Our data showed that CCL4 and CCL20 recruit functionally different T lymphocyte subsets into oesophageal carcinoma, indicating CCL4 and CCL20 are potential predictors of ESCC patients' survival.
Intumescent flame retardant (IFR) has received the considerable attention ascribed to the inherent advantages including non-halogen, low toxicity, low smoke release and environmentally friendly. In this work, a novel charring agent poly (piperazine phenylaminophosphamide) named as PPTA was successfully synthesized and characterized by Fourier transform infrared spectra (FTIR) and X-ray photoelectron spectroscopy (XPS). Then, a series of flame-retardant EP samples were prepared by blending with ammonium polyphosphate (APP) and PPTA. Combustion tests include oxygen Index (LOI), verticalBurning Test (UL-94) and cone calorimeter testing,these test results showed that PPTA greatly enhances the flame retardancy of EP/APP. According to detailed results, EP containing 10 wt% APP had a LOI value of 30.2%,but had no enhancement on UL-94 rating.However, after both 7.5 wt% APP and 2.5 wt% PPTA were added, EP-7 passed UL-94 V-0 rating with a LOI value of 33.0%. Moreover, the peak heat release rate (PHRR) and peak of smoke product rate (PSPR) of EP-7 were greatly decreased. Meanwhile, the flameretardant mechanism of EP-7 was investigated by scanning electron microscopy (SEM), thermogravimetric analysis/infrared spectrometry (TG-IR) and X-ray photoelectron spectroscopy (XPS). The corresponding results presented PPTA significantly increased the density of char layer, resulting in the good flame retardancy.
K E Y W O R D Sepoxy resin, flame retardancy, mechanism, thermal behavior
SummaryCD100 is an immune semaphorin constitutively expressed on T‐cells. Matrix metalloproteinase (MMP) is an important mediator of membrane‐bound CD100 (mCD100) cleavage to generate soluble CD100 (sCD100), which has immunoregulatory activity in immune cell responses. The aim of the study was to investigate the level and role of sCD100 and mCD100 in modulating CD8+ T‐cell function in non‐small cell lung cancer (NSCLC). sCD100 and MMP‐14 levels in the serum and bronchoalveolar lavage fluid (BALF), and mCD100 expression on peripheral and lung‐resident CD8+ T‐cells were analysed in NSCLC patients. The ability to induce sCD100 and the effect of MMP‐14 on mCD100 shedding for the regulation of non‐cytolytic and cytolytic functions of CD8+ T‐cells were also analysed in direct and indirect contact co‐culture systems. NSCLC patients had lower serum sCD100 and higher mCD100 levels on CD8+ T‐cells compared with healthy controls. BALF from the tumour site also had decreased sCD100 and increased mCD100 on CD8+ T‐cells compared with the non‐tumour site. Recombinant CD100 stimulation enhanced non‐cytolytic and cytolytic functions of CD8+ T‐cells from NSCLC patients, whereas blockade of CD100 receptor CD72 attenuated CD8+ T‐cell activity. NSCLC patients had lower MMP‐14 in the serum and in BALF from the tumour site. Recombinant MMP‐14 mediated mCD100 shedding from CD8+ T‐cell membrane, and led to promotion of CD8+ T‐cell response in NSCLC patients. Overall, decreased MMP‐14 resulted in insufficient CD100 shedding, leading to suppression of peripheral and lung‐resident CD8+ T‐cell activity in NSCLC.
In this review article, we have illustrated the strategies developed to achieve inorganic-organic hybrid compounds with technologically important physical properties. A series of target inorganic-organic hybrid compounds have been accomplished by incorporating the functional organic components (with a large hyperpolarizability and luminophore Schiff base cation) into the highly polarizable one-dimensional (1-D) iodoplumbate chain network. The effect of substituent features in the phenyl ring of the Schiff base cation on its molecular conformation as well as the crystal packing structure of the hybrid compound will be discussed and the multiple physical properties (ferroelectricity, NLO and multiple band emission) will also be mentioned.
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.