The rTCA cycle (also known as the reverse Krebs cycle) is a central anabolic biochemical pathway whose origins are proposed to trace back to geochemistry, long before the advent of enzymes, RNA or cells, and whose imprint still remains intimately embedded in the structure of core metabolism. If it existed, a primordial version of the rTCA cycle would necessarily have been catalyzed by naturally occurring minerals at the earliest stage of the transition from geochemistry to biochemistry. Here we report non-enzymatic promotion of multiple reactions of the rTCA cycle in consecutive sequence, whereby 6 of its 11 reactions are promoted by Zn2+, Cr3+ and Fe0 in an acidic aqueous solution. Two distinct three-reaction sequences can be achieved under a common set of conditions. Selectivity is observed for reduction reactions producing rTCA cycle intermediates compared to those leading off-cycle. Reductive amination of ketoacids to furnish amino acids is observed under similar conditions. The emerging reaction network supports the feasibility of primitive anabolism in an acidic, metal-rich reducing environment.

Highlights d GSK-3b inhibition-mediated hiPSC-cardiomyocyte proliferation is cell density dependent d GSK-3b inhibition with reduced cell-cell contact massively expands hiPSC-cardiomyocytes d LEF/TCF activity inhibits hiPSC-cardiomyocyte maturation without promoting cell cycling d Long-term expansion does not alter cardiomyocyte contractile function

CircRNA is a novel type of RNA molecule formed by a covalently closed loop which have no 5′-3′ polarity and possess no polyA tail and relatively stable due to the cyclic structure. Therefore, they may serve as potential targets and diagnosis biomarkers for tumor therapy. cZNF292 is an important circular oncogenic RNA and plays a critical role in the progression of tube formation. This study is aimed at exploring the role of cZNF292 in human glioma tube formation and its potential mechanism of action. We found that cZNF292 silencing suppresses tube formation by inhibiting glioma cell proliferation and cell cycle progression. Cell cycle progression in human glioma U87MG and U251 cells was halted at S/G2/M phase via the Wnt/β-catenin signaling pathway and related genes such as PRR11, Cyclin A, p-CDK2, VEGFR-1/2, p-VEGFR-1/2 and EGFR. The results suggest that cZNF292 silencing plays an important role in the tube formation process and has potential for application as a therapeutic target and biomarker in glioma.