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Chen Wenjia,Ma Zhaochen,Yu Lingxiang,MAO Xia,Ma Nan,Guo Xiaodong,Yin Xiaoli,Jiang Funeng,Wang Qian,Wang Jigang,Fang Mingliang,Lin Na,Zhang Yanqiong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Artesunate (ART) has been indicated as a candidate drug for hepatocellular carcinoma (HCC). Glucosylceramidase (GBA) is required for autophagic degradation. Whether ART regulates autophagic flux by targeting GBA in HCC remains to be defined. Herein, our data demonstrated that the dramatic overexpression of GBA was significantly associated with aggressive progression and short overall survival times in HCC. Subsequent experiments revealed an association between autophagic activity and GBA expression in clinical HCC samples, tumor tissues from a rat model of inflammation-induced HCC and an orthotopic mouse model, and human HCC cell lines. Interestingly, probe labeling identified GBA as an ART target, which was further verified by both a glutathione-S-transferase pulldown assay and surface plasmon resonance analysis. The elevated protein expression of LC3B, the increased numbers of GFP-LC3B puncta and double-membrane vacuoles, and the enhanced expression of SQSTM1/p62 indicated that the degradation of autophagosomes in HCC cells was inhibited by ART treatment. Both the in vitro and in vivo data revealed that autophagosome accumulation through targeting of GBA was responsible for the anti-HCC effects of ART. In summary, this preclinical study identified GBA as one of the direct targets of ART, which may have promising potential to inhibit lysosomal autophagy for HCC therapy.
Xin Yan,Jinxing Yu,Mingliang Ye,Kun He 대한기계학회 2023 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.37 No.8
A multi-rib design concept was proposed to reduce the heat transfer and enhance film cooling effect on squealer tip. Three different shapes of ribs (i.e. straight ribs, Vshape ribs, and L-shape ribs) were configured in the cavity of squealer tip of a turbine stage. The distributions of heat transfer coefficient (HTC) and film cooling effectiveness (FCE) on the multi-rib squealer tip were numerically predicted and compared against the conventional squealer tip. The results indicate that the configuration of multiple ribs is beneficial to weaken the development of cavity vortex system, and also traps more coolants in the squealer cavity. Compared to the conventional design, the implementation of L-shape ribs reduces the thermal loads on the cavity floor and entire tip by 82.4 % and 34.7 %, respectively, while the film cooling effects on the cavity floor and the entire tip are enhanced by 21.1 % and 72.2 %, respectively.
Malnutrition worsens fluorosis-induced damage in hypothalamic-pituitary-ovarian axis of rats
Yongmei Liu,Ling Li,Jingfeng Xu,Siwen Yu,Shijun Wang,Maojuan Yu,Wenbing Zou,Mingliang Cheng,Shuhua Xia 대한독성 유전단백체 학회 2019 Molecular & cellular toxicology Vol.15 No.2
Backgrounds: This study aimed to evaluate the effects of malnutrition on the hypothalamic-pituitary-ovarian axis (HPOA) sex hormones in female rats with coal burning-type fluorosis. Methods: Female rats were divided into four groups: control, malnutrition, fluorosis, and fluorosis with malnutrition. Rats in the control and malnutrition groups were fed pollution-free corn with either regular or low protein content. Rats in the fluorosis and fluorosis with malnutrition groups were fed corn roasted with coals from the fluorosis endemic areas of Zhijin, China,with either regular or low protein content. Results: Results revealed that the body weight of rats with protein malnutrition was significantly reduced compared with that of the control and fluorosis rats. Urinary fluoride was significantly decreased and bone fluoride was significantly increased in the fluorosis with malnutrition group compared to the fluorosis group. Moreover, protein malnutrition significantly enhanced the effect of fluoride on gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, and testosterone. Histological and ultrastructural analyses revealed that protein malnutrition intensified fluoride-induced ovary damage. Conclusion: Malnourishment could promote the abnormal secretion of HPOA sex hormones in females with fluorosis.
Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells
Zhu, Saiyong,Ambasudhan, Rajesh,Sun, Woong,Kim, Hyun Jung,Talantova, Maria,Wang, Xiaojing,Zhang, Mingliang,Zhang, Yu,Laurent, Timothy,Parker, James,Kim, Han-Seop,Zaremba, Jeffrey D,Saleem, Sofiyan,San Springer Science and Business Media LLC 2014 Cell research Vol.24 No.1
Chlorogenic acid accumulation and related gene expression in peach fruit
Yan Juan,Su Ziwen,Guo Shaolei,Zhang Minghao,Zhang Binbin,Cai Zhixiang,Shen Zhijun,Ma Ruijuan,Yu Mingliang 한국원예학회 2022 Horticulture, Environment, and Biotechnology Vol.63 No.3
To reveal the molecular mechanism in the accumulation of chlorogenic acids (CGAs) in peach (Prunus persica) fruit during growth and development, CGA contents in the flesh of the three peach cultivars ‘Ruiguang 18’, ‘Heiyoutao’, and ‘Beijingyixianhong’ were determined. The expression levels of CGA metabolism-related genes were analyzed based on transcriptome data (RNA-seq). These candidate genes were then screened and real-time fluorescent quantitative PCR (qRT-PCR) was performed to verify their expression. The results showed that the content of total CGAs, 5-O-caffeoylquinic acid and 3-O-caffeoylquinic acid, in the flesh of ‘Ruiguang 18’ exhibited a decreasing trend during fruit development, and there was a great drop at maturity stage (P < 0.05). The three contents in ‘Heiyoutao’ increased first at stage S2 (P < 0.05) and then decreased significantly (P < 0.05). In ‘Beijingyixianhong’, they stayed stable in the early stages, then total CGAs and 3-O-caffeoylquinic acid decreased significantly at the maturity stage (P < 0.05). RNA-seq transcriptome data analysis and qRT-PCR expression analysis showed that the accumulation of CGAs in fruit flesh was mainly affected by the expression of Prupe.3G100800 (PpHCT) and Prupe.3G107300 (Pp4CL), and their expression levels were highly consistent with total CGA content. Thus, we concluded that Prupe.3G100800 (PpHCT) and Prupe.3G107300 (Pp4CL) are the key genes for CGAs synthesis in peach flesh.