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Objective: To assess whether smoking increases the risk of bleeding in patients with cerebral arteriovenous malformations (CAVM).Material and Methods: According to our research plan, 385 CAVM patients admitted to Beijing Tiantan Hospital from December 2015 to January 2018 were included in this study, including 210 bleeding patients and 175 non-bleeding patients. We divided patients into three subgroups of current smokers, ex-smokers (those who quit smoking for one year or more) and non-smokers. The relationship between smoking and the risk of CAVM rupture was assessed by univariate and multivariate regression analysis.Results: Multivariate regression analysis showed that there was a statistically significant difference between current smoker and non-smoker (OR = 1.87, p = 0.019). Among the covariates of the multivariate regression analysis, the location, combined with blood flow-related intracranial aneurysms and size were related to the risk of CAVM bleeding.Conclusion: Current smoking may increase the risk of CAVM bleeding; however, there was no significant correlation between ex-smoking and CAVM bleeding. [ABSTRACT FROM AUTHOR]

Joint improvement of the Seebeck coefficient S and conductivity σ is a pressing issue to overcome the limit of the figure of merit ( ZT ) enhancement of thermoelectric materials. This study presents a joint improvement in the ZnO:Al films by tuning the diffusion of Au layer via substrate temperature, using a radio frequency-assisted molecular beam vapor deposition method. The phenomenon occurs in the ZnO:Al films at the room temperature (RT) substrate deposited on a 10 nm Au layer (RT-ZnO:AuAl). The films have a hexagonal wurtzite structure with an in-plane (002) preferred orientation and smooth surface. The resistivity values of the films are at the same magnitude of the transparent conducting oxide (~10 −6  Ω·m). The carrier concentration reaches 2.60 × 10 21  cm −3 for the RT-ZnO:AuAl film. The S is about 29.5 μV/K at 240 °C. Joint improvement of conductivity and Seebeck coefficient makes the PF of the RT-ZnO:AuAl film reaches 3.58 × 10 −5  Wm −1  K −2 , which is two orders of magnitude larger than that of the RT-ZnO:Au film without joint improvement. The results indicate that the higher conductivity originates from the Au layer, in-plane (002) preferred orientation, and the easily excited carriers in the ZnO:Al due to the low binding energy of the Zn 2p electrons. The large S in the film is related to the high effective masses due to the impact of the diffusion of the Au layer on electronic interactions. [ABSTRACT FROM AUTHOR]

Abstract Al-doped ZnO films (Zn 0.94 Al 0.06 O x) can be fabricated by thermal oxidation of evaporated metallic Zn-Al film. Oxygen defects were strongly related to oxygen pressure at a given temperature (500 °C) and duration (3 h). Under oxygen pressure of 0.021 MPa (O 2 -0.021 MPa), the main component was the Zn phase. Zn 0.94 Al 0.06 O x films were formed under oxygen pressure of 0.1 MPa and 0.12 MPa, with the conductivity and Seebeck coefficient improving simultaneously with increased oxygen pressure. The flat particles of the O 2 -0.12 MPa film weakened the electron scattering, leading to increased conductivity. Furthermore, the decrease in oxygen vacancies caused by the higher oxygen pressure increased the Seebeck coefficient. As a result, the power factor of the O 2 -0.12 MPa film was about 30 times greater than that of the O 2 -0.1 MPa film, characterized by an increasing content of singly ionised oxygen. Highlights • Carrier concentration was changed by oxygen pressure in thermal oxidation. • Power factor was affected by content of single ionised oxygen. • Conductivity and Seebeck coefficient increased simultaneously with oxygen pressure. [ABSTRACT FROM AUTHOR]

We aimed to investigate the effects of bone marrow mesenchymal stem cell conditioned medium (BMSC-CM) in preventing 2,5-hexanedione (HD)-induced damage to motoneurons, and examined the molecular mechanisms that mediate these effects. VSC4.1 cells were exposed to 25 mM HD for 24 h followed by incubation with DMEM for 24 h. HD-treated cells were incubated with BMSC-CM at varied concentrations. Incubation with BMSC-CM ameliorated the decreased cell viability and reduced LDH release from cells exposed to HD. BMSC-CM suppressed the elevated number of autophagic vacuoles, cells with LC3 puncta, increased LC3-II/LC3-I ratio, and decreased p62 caused by HD exposure. BMSC-CM elevated NGF and p-TrkA expressions in HD-treated cells. Administration of NGF inhibited autophagy, an effect that was similar to that observed after BMSC-CM treatment; this effect was abolished by the addition of NGF-neutralizing antibodies. BMSC-CM or NGF elevated p-protein kinase B (Akt) and p-mammalian target of rapamycin (mTOR) in HD-exposed cells, which was interrupted by TrkA inhibitor, K252a and mTOR inhibitor, rapamycin. BMSC-CM prevented HD-induced autophagic cell damage in VSC4.1 cells. The neuroprotective effect of BMSC-CM appeared to be at least partly associated with its ability to trigger the NGF-phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Protein kinase C delta (PKC-δ ) has been identified as a tumor suppressor. However, the effects of PKC-δ on the cancer stem cells in squamous cell carcinomas (SCC) have not been clarified. The purpose of this study was to detect the regulation of PKC-δ on cancer stem cell among SSC cells and the role of p63 during the regulation. Immunohistochemistry of human cutaneous SCC tissues was performed to detect the expression of PKC-δ. After the human SCC13 cells infected by recombinant adenoviruses, the cell proliferation were determined. The correlation of PKC-δ and p63 was detected by western blot. The colony forming activity and the number of cancer stem cells (CSCs) in SCC identified by double-staining with anti-integrin α 6 and anti-CD71 antibodies were detected. The expression of PKC-δ was obviously decreased in SCC tissues compared with that in normal skin tissues. The higher protein level of p63 in SCC was attenuated by the transfection of PKC-δ. The higher proliferation capacity of SCC13 cells, the higher activity and expression of CSCs in SCC13 cells induced by p63 were significantly suppressed by the transfection of PKC-δ. In conclusion, PKC-δ played as a protective role in SCC partly by down-regulating p63, leading to the suppression of SCC cell proliferation, attenuation of the activity and expression of CSCs in SCC cells. [ABSTRACT FROM AUTHOR]

Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials. However, the underlying mechanism remains to be elucidated. Here we show that LGX818 potently decreased ERK phosphorylation and inhibited proliferation in BRAFV600E melanoma cell lines. Moreover, LGX818 downregulated CyclinD1 in a glycogen synthase kinase 3β-independent manner and induced cell cycle arrest in the G1 phase, Surprisingly, LGX818 triggered cellular senescence in BRAFV600E melanoma cells, as evidenced by increased β-galactosidase staining, while no appreciable induction of apoptosis was detected, as determined by Annexin V and propidium iodide staining and immunoblot analysis of caspase-3 processing and poly (ADP-ribose) polymerase cleavage. Increased p27KIP1 expression and retinoblastoma protein activation were detected during LGX818-induced senescence. Additionally, inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 1B by AZ191 reversed LGX818-induced CyclinD1 turnover and senescence. Interestingly, autophagy is triggered through inhibition of the mTOR/70S6K pathway during LGX818-induced senescence. Moreover, autophagy inhibition by pharmacological and genetic regulation attenuates LGX818-induced senescence. Notably, combining LGX818 with autophagy modulators has anti-proliferative effect in LGX818-resistant BRAF mutant melanoma cells. Altogether, we uncovered a mechanism by which LGX818 exerts its anti-tumor activity in BRAFV600E melanoma cells. [ABSTRACT FROM AUTHOR]

Multi-nanocomposite is an effective method to achieve high thermoelectric (TE) performance by breaking the tradeoff among three TE parameters. This paper presents a comparative study of incorporated carbon nanotube (CNT)/Au in evaporated porous Al-doped ZnO (AZO) films. The effect of the nanocomposite interface on scattering of carriers and phonons is used to independently tune thermal conductivity and power factor in the multi-nanocomposite AZO films. This breaks the tradeoff and improves the figure of merit (ZT) of the film. Moreover, the temperature gradient retains in the out-of-plane of the films. These make the AZO film composited CNT and porosity have higher output power than that of the non-porous films. This provides a simple method for the low-dimension film to increase the TE properties through breaking the tradeoff and makes the TE materials suitable for efficient harvesting in low-grade waste heat. [Display omitted] • This study presents a simple method to prepare multi-nanocomposite film. • Multi-nanocomposite breaks the tradeoff among thermoelectric parameters. • Film with CNT and porosity has higher ZT value and output power. [ABSTRACT FROM AUTHOR]