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131.
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Zhongyi Fan Jingjing Duan Pu Luo Ling Shao Qiong Chen Xiaohua Tan Lei Zhang Xiaojie Xu 《Cell death & disease》2022,13(4)
Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.Subject terms: GSE22138Eye cancer, Prognostic markers 相似文献
133.
Yuting Zhang Hongxia Gao Xiaohui Hu Qisheng Wang Fanglin Zhong Xuelan Zhou Cheng Lin Yang Yang Junkang Wei Weian Du Huaiqiu Huang Huan Zhou Wei He Hua Zhang Yuting Zhang Peter J. McCormick Jinheng Fu Dan Wang Yang Fu Xiaolu Lu Tengfei Zhang Jingjing Duan Bingjie Qin Haihai Jiang Jun Luo Yan Zhang Qi Chen Qunfeng Luo Lin Cheng Zheng Zhang Jin Zhang Jian Li 《Journal of virology》2022,96(1)
134.
Kun Yang Min Fan Xiaohui Wang Jingjing Xu Yana Wang Fei Tu P. Spencer Gill Tuanzhu Ha Li Liu David L. Williams Chuanfu Li 《Cell death and differentiation》2022,29(1):133
High circulating levels of lactate and high mobility group box-1 (HMGB1) are associated with the severity and mortality of sepsis. However, it is unclear whether lactate could promote HMGB1 release during sepsis. The present study demonstrated a novel role of lactate in HMGB1 lactylation and acetylation in macrophages during polymicrobial sepsis. We found that macrophages can uptake extracellular lactate via monocarboxylate transporters (MCTs) to promote HMGB1 lactylation via a p300/CBP-dependent mechanism. We also observed that lactate stimulates HMGB1 acetylation by Hippo/YAP-mediated suppression of deacetylase SIRT1 and β-arrestin2-mediated recruitment of acetylases p300/CBP to the nucleus via G protein-coupled receptor 81 (GPR81). The lactylated/acetylated HMGB1 is released from macrophages via exosome secretion which increases endothelium permeability. In vivo reduction of lactate production and/or inhibition of GPR81-mediated signaling decreases circulating exosomal HMGB1 levels and improves survival outcome in polymicrobial sepsis. Our results provide the basis for targeting lactate/lactate-associated signaling to combat sepsis.Subject terms: Infectious diseases, Signal transduction, Epigenetics 相似文献
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工程教育是我国高等教育的重要组成部分,随着新工科人才培养内涵的不断深化,全方位开展课程改革,提高工科人才培养质量正当其时。为了突出新工科人才培养的特色,专业课和实习实践类课程正在成为课程教学改革的重点。但是,在专业基础课中如何突出工科特色人才培养的实践亟待探索。本文以生物化学课程为例,采用问题引导式教学方法,选择合适的教学案例,从科学与技术问题出发探索教学设计,引导学生凝练问题、分析问题并解决问题。实现引导学生从“被动式”到“主动式”学习的转变,提升学生思辨能力的同时,突出科学与技术的工程化应用,并为持续甚至终生学习奠定基础,为新工科背景下应用型人才培养提供参考和借鉴。 相似文献
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Brown CR Liu J Hung GC Carter D Cui D Chiang HL 《The Journal of biological chemistry》2003,278(28):25688-25699
The key gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase) is targeted to Vid vesicles when glucose-starved cells are replenished with glucose. Vid vesicles then deliver FBPase to the vacuole for degradation. A modified alkaline phosphatase assay was developed to study the trafficking of Vid vesicles to the vacuole. For this assay, FBPase was fused with a truncated form of alkaline phosphatase. Under in vivo conditions, FBPase-delta60Pho8p was targeted to the vacuole via Vid vesicles, and it exhibited Pep4p- and Vid24p-dependent alkaline phosphatase activation. Vid vesicle-vacuole targeting was reconstituted using Vid vesicles that contained FBPase-delta60Pho8p. These vesicles were incubated with vacuoles in the presence of cytosol and an ATP-regenerating system. Under in vitro conditions, alkaline phosphatase was also activated in a Pep4p- and Vid24p-dependent manner. The GTPase Ypt7p was identified as an essential component in Vid vesicle-vacuole trafficking. Likewise, a number of v-SNAREs (Ykt6p, Nyv1p, Vti1p) and homotypic fusion vacuole protein sorting complex family members (Vps39p and Vps41p) were required for the proper function of Vid vesicles. In contrast, the t-SNARE Vam3p was a necessary vacuolar component. Vid vesicle-vacuole trafficking exhibits characteristics similar to heterotypic membrane fusion events. 相似文献
140.
The high activity of T7 RNA polymerase has made the T7 RNA polymerase-based expression system very powerful for high-level expression of recombinant protein. However, the overactivity of T7 RNA polymerase would also bring about negative effects on plasmid stability and protein production, especially when expressing a toxic protein. If the latter role is dominant, it is necessary to adopt some measures to attenuate the activity or the amount of T7 RNA polymerase in the cells. Apart from the stringent regulation by inserting some genes reducing the amount or the activity of T7 RNA polymerase into plasmids, optimizing the culture conditions would be another way. In this work, we have studied the effects of various culture conditions on the plasmid stability and the target protein yield including selective pressure, culture temperature, toxicity of the target protein and the catabolite repression caused by glucose. The results have indicated that adding antibiotic after induction has little effect in increasing plasmid stability, but inducing expression at low temperature and adding glucose to the medium improved the plasmid stability and the protein yield to a large extent. 相似文献