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        Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway

        Zhou Meng-jiao,Yang Jia-jie,Ma Ting-yao,Feng Ge-xuan,Wang Xue-lian,Wang Li-Yong,Ge Yu-ze,Gao Ran,Hong-liang Liu,Shan Lin,Kong Lu,Chen Xiao-hong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

        MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the “MYC_TARGETS_V2” gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the “MYC_TARGETS_V2” gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.

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        Mitochondrial NDUFA4L2 attenuates the apoptosis of nucleus pulposus cells induced by oxidative stress via the inhibition of mitophagy

        Wen-Ning Xu,Huo-Liang Zheng,Run-Ze Yang,Tao Liu,Wei Yu,Xin-Feng Zheng,Bo Li,Sheng-Dan Jiang,Lei-Sheng Jiang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

        The main pathological mechanism of intervertebral disc degeneration (IVDD) is the programmed apoptosis of nucleus pulposus (NP) cells. Oxidative stress is a significant cause of IVDD. Whether mitophagy is induced by strong oxidative stress in IVDD remains to be determined. This study aimed to investigate the relationship between oxidative stress and mitophagy and to better understand the mechanism of IVDD in vivo and in vitro. To this end, we obtained primary NP cells from the human NP and subsequently exposed them to TBHP. We observed that oxidative stress induced mitophagy to cause apoptosis in NP cells, and we suppressed mitophagy and found that NP cells were protected against apoptosis. Interestingly, TBHP resulted in mitophagy through the inhibition of the HIF-1α/NDUFA4L2 pathway. Therefore, the upregulation of mitochondrial NDUFA4L2 restricted mitophagy induced by oxidative stress. Furthermore, the expression levels of HIF-1α and NDUFA4L2 were decreased in human IVDD. In conclusion, these results demonstrated that the upregulation of NDUFA4L2 ameliorated the apoptosis of NP cells by repressing excessive mitophagy, which ultimately alleviated IVDD. These findings show for the first time that NDUFA4L2 and mitophagy may be potential therapeutic targets for IVDD.

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        Effects of graphite additives in electrolytes on the microstructure and corrosion resistance of Alumina PEO coatings

        Guo-Hua Lv,Huan Chen,Wei-Chao Gu,Wen-Ran Feng,Li Li,Er-Wu Niu,Xian-Hui Zhang,Si-Ze Yang 한국물리학회 2009 Current Applied Physics Vol.9 No.3

        In the present work, graphite grains of different sizes were added into the electrolyte to prepare ceramic coatings on aluminum by plasma electrolytic oxidation (PEO). Scanning electron microscopy (SEM) coupled with an energy dispersive X-ray analysis system (EDX), Raman spectroscopy and X-ray diffractometer (XRD) were used to characterize the coatings. A three-electrode system was used to evaluate the corrosion performances of the coatings in a 3.5 wt.% NaCl solution. It was found that the morphology and corrosion performance of the coatings were significantly influenced by the size of the graphite grains. Compared with bigger graphite grains, finer ones were involved in the oxidation process and embedded within the ceramic coatings, which made the coatings less porous and more compact. Thus, the corrosion resistance of the coatings with embedded graphite grains was greatly improved. In the present work, graphite grains of different sizes were added into the electrolyte to prepare ceramic coatings on aluminum by plasma electrolytic oxidation (PEO). Scanning electron microscopy (SEM) coupled with an energy dispersive X-ray analysis system (EDX), Raman spectroscopy and X-ray diffractometer (XRD) were used to characterize the coatings. A three-electrode system was used to evaluate the corrosion performances of the coatings in a 3.5 wt.% NaCl solution. It was found that the morphology and corrosion performance of the coatings were significantly influenced by the size of the graphite grains. Compared with bigger graphite grains, finer ones were involved in the oxidation process and embedded within the ceramic coatings, which made the coatings less porous and more compact. Thus, the corrosion resistance of the coatings with embedded graphite grains was greatly improved.

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