SUMMARY Decades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM) differentiation. However, control of CM maturation which is subsequently required to generate adult myocytes, remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and identified a large number of genes whose expression shifts gradually and continuously during maturation. We generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs), which show discrete sets of key transcriptional regulators and pathways activated or suppressed during CM maturation. We developed a GRN-based program named MatStatCM that indexes CM maturation status. MatStatCM reveals that pluripotent stem cell-derived CMs mature early in culture, but are arrested at the late embryonic stage with aberrant regulation of key transcription factors. Our study provides a foundation for understanding CM maturation.

The modulated synthesis of metal−organic frameworks (MOFs) remains empirical and challenging. Modulators are often applied and assumed capable of facilitating crystal growth by adjusting the reaction kinetics. However, most of the current studies are based on qualitative analysis and performance-leading synthesis, while no quantitative insights between modulator feature and MOF performance have been offered. In this work, we carried out a comprehensive study of the effects of three modulators (acetic acid, formic acid, trifluoroacetic acid) on the water-based modulated synthesis of UiO-66-type MOFs by using Zr or Hf as the building block and fumarate as the ligand. The modulator effects on crystallinity, yield, morphology, pore size, defects, porosity, stability, and gas separation performance of resultant MOFs have been discussed. A relationship between optimal molar ratio y and pK a value of modulator x is modeled as y = 12.72 + 0.193 × exp(1.276x). For MOF synthesis using ligands of different acidity, it tends to follow the equations of y = −40.78 + 39.1x and y = −21.7 + 25.58x for acetic acid and formic acid, respectively. Our results have thus provided pioneering quantitative analysis and synthetic guidelines on the further synthesis of water-stable MOFs that require modulators.

Vascular morphogenesis is the formation of endothelial lumenized networks. Cluster-based vasculogenesis of endothelial progenitor cells (EPCs) has been observed in animal models, but the underlying mechanism is unknown. Here, using O2-controllabe hydrogels, we unveil the mechanism by which hypoxia, co-jointly with matrix viscoelasticity, induces EPC vasculogenesis. When EPCs are subjected to a 3D hypoxic gradient ranging from <2 to 5%, they rapidly produce reactive oxygen species that up-regulate proteases, most notably MMP-1, which degrade the surrounding extracellular matrix. EPC clusters form and expand as the matrix degrades. Cell-cell interactions, including those mediated by VE-cadherin, integrin-β2, and ICAM-1, stabilize the clusters. Subsequently, EPC sprouting into the stiffer, intact matrix leads to vascular network formation. In vivo examination further corroborated hypoxia-driven clustering of EPCs. Overall, this is the first description of how hypoxia mediates cluster-based vasculogenesis, advancing our understanding toward regulating vascular development as well as postnatal vasculogenesis in regeneration and tumorigenesis.

The strategy to functionalize water-stable metal-organic frameworks (MOFs) in order to improve their CO2 uptake capacities for efficient CO2 separation remains limited and challenging. We herein present an effective approach to functionalize a prominent water-stable MOF, UiO-66(Zr), by a combination of optimization and metalated-ligand exchange. In particular, by systematic optimization, we have successfully obtained UiO-66(Zr) of the highest BET surface area reported so far (1730 m(2)  g(-1) ). Moreover, it shows a hybrid Type I/IV N2 isotherm at 77 K and a mesopore size of 3.9 nm for the first time. The UiO-66 MOF underwent a metalated-ligand-exchange (MLE) process to yield a series of new UiO-66-type MOFs, among which UiO-66-(COONa)2 -EX and UiO-66-(COOLi)4 -EX MOFs have both enhanced CO2 working capacity and IAST CO2 /N2 selectivity. Our approach has thus suggested an alternative design to achieve water-stable MOFs with high crystallinity and gas uptake for efficient CO2 separation.