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  • American Association for the Advancement of Science (AAAS)  (2)
  • Li, Yin  (2)
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  • American Association for the Advancement of Science (AAAS)  (2)
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  • 1
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2019
    In:  Science Translational Medicine Vol. 11, No. 495 ( 2019-06-05)
    In: Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 11, No. 495 ( 2019-06-05)
    Abstract: Progressive peritoneal fibrosis affects patients receiving peritoneal dialysis (PD) and has no reliable treatment. The mechanisms that initiate and sustain peritoneal fibrosis remain incompletely elucidated. To overcome these problems, we developed a strategy that prevents peritoneal fibrosis by suppressing PD-stimulated mesothelial-to-mesenchymal transition (MMT). We evaluated single-cell transcriptomes of mesothelial cells obtained from normal peritoneal biopsy and effluent from PD-treated patients. In cells undergoing MMT, we found cellular heterogeneity and intermediate transition states associated with up-regulation of enzymes involved in glycolysis. The expression of glycolytic enzymes was correlated with the development of MMT. Using gene expression profiling and metabolomics analyses, we confirmed that PD fluid induces metabolic reprogramming, characterized as hyperglycolysis, in mouse peritoneum. We found that transforming growth factor β1 (TGF-β1) can substitute for PD fluid to stimulate hyperglycolysis, suppressing mitochondrial respiration in mesothelial cells. Blockade of hyperglycolysis with 2-deoxyglucose (2-DG) inhibited TGF-β1–induced profibrotic cellular phenotype and peritoneal fibrosis in mice. We developed a triad of adeno-associated viruses that overexpressed microRNA-26a and microRNA-200a while inhibiting microRNA-21a to target hyperglycolysis and fibrotic signaling. Intraperitoneal injection of the viral triad inhibited the development of peritoneal fibrosis induced by PD fluid in mice. We conclude that hyperglycolysis is responsible for MMT and peritoneal fibrogenesis, and this aberrant metabolic state can be corrected by modulating microRNAs in the peritoneum. These results could provide a therapeutic strategy to combat peritoneal fibrosis.
    Type of Medium: Online Resource
    ISSN: 1946-6234 , 1946-6242
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
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  • 2
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Vol. 373, No. 6562 ( 2021-09-24), p. 1523-1527
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 373, No. 6562 ( 2021-09-24), p. 1523-1527
    Abstract: Starches, a storage form of carbohydrates, are a major source of calories in the human diet and a primary feedstock for bioindustry. We report a chemical-biochemical hybrid pathway for starch synthesis from carbon dioxide (CO 2 ) and hydrogen in a cell-free system. The artificial starch anabolic pathway (ASAP), consisting of 11 core reactions, was drafted by computational pathway design, established through modular assembly and substitution, and optimized by protein engineering of three bottleneck-associated enzymes. In a chemoenzymatic system with spatial and temporal segregation, ASAP, driven by hydrogen, converts CO 2 to starch at a rate of 22 nanomoles of CO 2 per minute per milligram of total catalyst, an ~8.5-fold higher rate than starch synthesis in maize. This approach opens the way toward future chemo-biohybrid starch synthesis from CO 2 .
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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