The heart switches its energy substrate from glucose to fatty acids at birth, and maternal hyperglycemia is associated with congenital heart disease. However, little is known about how blood glucose impacts heart formation. Using a chemically defined human pluripotent stem-cell-derived cardiomyocyte differentiation system, we found that high glucose inhibits the maturation of cardiomyocytes at genetic, structural, metabolic, electrophysiological, and biomechanical levels by promoting nucleotide biosynthesis through the pentose phosphate pathway. Blood glucose level in embryos is stable in utero during normal pregnancy, but glucose uptake by fetal cardiac tissue is drastically reduced in late gestational stages. In a murine model of diabetic pregnancy, fetal hearts showed cardiomyopathy with increased mitotic activity and decreased maturity. These data suggest that high glucose suppresses cardiac maturation, providing a possible mechanistic basis for congenital heart disease in diabetic pregnancy.

Four kinds of green deep eutectic solvent (DES) were synthesized, including choline chloride (ChCl)-urea, tetramethylammonium chloride (TMACl)-urea, tetrapropylammonium bromide (TPMBr)-urea and ChCl-methylurea. An aqueous two-phase system (ATPS) based ChCl-urea DES was studied for the first time for the extraction of bovine serum albumin (BSA). Single factor experiments proved that the extraction efficiency of BSA was influenced by the mass of the DES, concentration of K2HPO4 solution, separation time and extraction temperature. The optimum conditions were determined through an orthogonal experiment with the four factors described above. The results showed that under the optimum conditions, the average extraction efficiency could reach up to 99.94%, 99.72%, 100.05% and 100.05% (each measured three times). The relative standard deviations (RSD) of extraction efficiencies in precision, repeatability and stability experiments were 0.5533% (n = 5), 0.8306% (n = 5) and 0.9829% (n = 5), respectively. UV-vis and FT-IR spectra confirmed that there were no chemical interactions between BSA and the DES in the extraction process, and the CD spectra proved that the conformation of BSA did not change after extraction. The conductivity, DLS and TEM were combined to investigate the microstructure of the top phase and the possible mechanism for the extraction. The results showed that hydrophobic interactions, hydrogen bonding interactions and the salting-out effect played important roles in the transfer process, and the aggregation and surrounding phenomenon were the main driving forces for the separation. All of these results proved that ionic liquid (IL)-based ATPSs could potentially be substituted with DES-based ATPSs to offer new possibilities in the extraction of proteins.

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Cobalt inhibits prolyl hydroxylases, leading to the accumulation of hypoxia-inducible factor-1␣ (HIF-1␣) and a concomitant increase in the transcriptional activity of HIF-1. Therefore, cobalt has been under development as a drug for activating HIF-1 under some disease conditions. However, it has been shown that ischemic conditions resulted in the loss of copper, and the activation of HIF-1 would not occur unless copper was supplemented. The present study was undertaken to test the hypothesis that copper is also required for the cobalt activation of HIF-1 transcriptional activity. Human umbilical vein endothelial cells subjected to treatment with cobalt chloride (CoCl 2 ) at concentrations above 25 M for 2 h resulted in an accumulation of HIF-1␣, which was determined by Western blot analysis, and an increase in the expression of vascular endothelial growth factor (VEGF), which was determined by real-time reverse transcription-polymerase chain reaction analysis for mRNA levels and enzyme-linked immunosorbent assay analysis for protein levels. The copper chelator tetraethylenepentamine at 25 M did not significantly affect the accumulation of HIF-1␣ but blocked increases in VEGF mRNA and protein levels, an effect that could be reversed by the addition of 25 M copper sulfate (CuSO 4 ). In addition, gene silencing of the copper chaperone for Cu,Zn-superoxide dismutase blocked VEGF expression with little effect on cobalt-induced HIF-1␣ accumulation. The present study thus demonstrates that copper was required for cobalt-activated transcriptional activity of HIF-1, although copper did not affect cobalt-induced accumulation of HIF-1␣ in the cells.

Porous ultrathin 2D catalysts are attracting great attention in the field of electro/photocatalytic hydrogen evolution reaction (HER) and overall water splitting. Herein, a universal pH-controlled wet-chemical strategy is reported followed by thermal and phosphorization treatment to prepare large-size, porous and ultrathin bimetallic phosphide (NiCoP) nanosheets, in which graphene oxide is adopted as a template to determine the size of products. The thickness of the resultant NiCoP nanosheets ranges from 3.5 to 12.8 nm via delicately adjusting pH from 7.8 to 8.5. The thickness-dependent electrocatalytic performance is evidenced experimentally and explained by computational studies. The prepared large-size ultrathin NiCoP nanosheets show excellent bifunctional electrocatalytic activity for overall water splitting, with low overpotentials of 34.3 mV for HER and 245.0 mV for oxygen evolution reaction, respectively, at 10 mA cm −2 . Furthermore, the NiCoP nanosheets exhibit superior photocatalytic HER performance, achieving a high HER rate of 238.2 mmol h −1 g −1 in combination with commonly used photocatalyst CdS, which is far superior to that of Pt/CdS (81.7 mmol h −1 g −1 ). All these results demonstrate large-size porous ultrathin NiCoP nanosheets as an efficient and multifunctional electro/photocatalyst for water splitting.