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The synergism between cardiomyogenesis and angiogenesis is essential for cardiac regeneration. Circular RNAs (circRNAs) play pivotal roles in cell growth and angiogenesis, but their functions in cardiac regeneration are not yet known. In this study, we investigated the role and underlying mechanisms of circRNA Hipk3 (circHipk3) in both cardiomyogenesis and angiogenesis during cardiac regeneration. We found that circHipk3 was overexpressed in the fetal or neonatal heart of mice. The transcription factor Gata4 bound to the circHipk3 promoter and increased circHipk3 expression. Cardiomyocyte (CM) proliferation in vitro and in vivo was inhibited by circHipk3 knockdown and increased by circHipk3 overexpression. Moreover, circHipk3 overexpression promoted coronary vessel endothelial cell proliferation, migration, and tube-forming capacity and subsequent angiogenesis. More importantly, circHipk3 overexpression attenuated cardiac dysfunction and decreased fibrotic area after myocardial infarction (MI). Mechanistically, circHipk3 promoted CM proliferation by increasing Notch1 intracellular domain (N1ICD) acetylation, thereby increasing N1ICD stability and preventing its degradation. In addition, circHipk3 acted as a sponge for microRNA (miR)-133a to promote connective tissue growth factor (CTGF) expression, which activated endothelial cells. Our findings suggested that circHipk3 might be a novel therapeutic target for preventing heart failure post-MI.

Due to its inherent superior perpendicular magnetocrystalline anisotropy, the FePt in L10 phase enables magnetic storage and memory devices with ultrahigh capacity. However, reversing the FePt magnetic state, and therefore encoding information, has proven to be extremely difficult. Here, it is demonstrated that an electric current can exert a large spin torque on an L10 FePt magnet, ultimately leading to reversible magnetization switching. The spin torque monotonically increases with increasing FePt thickness, exhibiting a bulk characteristic. Meanwhile, the spin torque effective fields and switching efficiency increase as the FePt approaches higher chemical ordering with stronger spin–orbit coupling. The symmetry breaking that generates spin torque within L10 FePt is shown to arise from an inherent structural gradient along the film normal direction. By artificially reversing the structural gradient, an opposite spin torque effect in L10 FePt is demonstrated. At last, the role of the disorder gradient in generating a substantial torque in a single ferromagnet is supported by theoretical calculations. These results will push forward the frontier of material systems for generating spin torques and will have a transformative impact on magnetic storage and spin memory devices with simple architecture, ultrahigh density, and readily application.

Arthrobacter pascens ZZ21 is a plant-beneficial, fluoranthene-degrading bacterial strain found in the rhizosphere. The production of the phytohormone indole-3-aectic acid (IAA) by ZZ21 is thought to contribute to its ability to promote plant growth and remediate fluoranthene-contaminated soil. Using genome-wide analysis combined with metabolomic and high-performance liquid chromatography-mass spectrometry (HPLC-MS) analyses, we characterized the potential IAA biosynthesis pathways in A. pascens ZZ21. IAA production increased 4.5-fold in the presence of 200 mg·L−1 tryptophan in the culture medium. The transcript levels of prr and aldH, genes which were predicted to encode aldehyde dehydrogenases, were significantly upregulated in response to exogenous tryptophan. Additionally, metabolomic analysis identified the intermediates indole-3-acetamide (IAM), indole-3-pyruvic acid (IPyA), and the enzymatic reduction product of the latter, indole-3-lactic acid (ILA), among the metabolites of ZZ21, and subsequently also IAM, ILA, and indole-3-ethanol (TOL), which is the enzymatic reduction product of indole-3-acetaldehyde, by HPLC-MS. These results suggest that the tryptophan-dependent IAM and IPyA pathways function in ZZ21.

AimsLong noncoding RNAs (lncRNAs) are critical regulators of cardiovascular lineage commitment and heart wall development, but their roles in regulating endogenous cardiac regeneration are unclear. The present study investigated the role of human-derived lncRNA in regulating endogenous cardiac regeneration as well as the underlying mechanisms.Methods and resultsWe compared RNA sequencing data from human foetal and adult hearts and identified a novel lncRNA that was upregulated in adult hearts (Genesymbol NONHSAG000971/NONHSAT002258 or ENST00000497710.5), which was a splice variant of the AZIN2 gene (AZIN2-sv). We used quantitative PCR to confirm the increased expression of AZIN2-sv in adult rat hearts. Coexpression network analysis indicated that AZIN2-sv could regulate proliferation. Loss- and gain-of-function approaches demonstrated that AZIN2-sv negatively regulated endogenous cardiomyocyte proliferation in vitro and in vivo. Knockdown of AZIN2-sv attenuated ventricular remodelling and improved cardiac function after myocardial infarction. Phosphatase and tensin homolog (PTEN) was identified as a target of AZIN2-sv, their direct binding increased PTEN stability. Furthermore, AZIN2-sv acted as a microRNA-214 sponge to release PTEN, which blocked activation of the PI3 kinase/Akt pathway to inhibit cardiomyocyte proliferation.ConclusionsThe newly discovered AZIN2-sv suppressed endogenous cardiac regeneration by targeting the PTEN/Akt pathway. Thus, AZIN2-sv may be a novel therapeutic target for preventing and treating heart failure.

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challenging but highly attractive for multitudinous applications, including molecular sieving technologies, drug delivery, and electronics. [1][2][3] Recently, noteworthy successes have been reported in the design and synthesis of porous organic cages [1,2] and metal-organic polyhedrons [4][5][6] with well-defined pore space and high solubility/dispersity in bulky solvents. Metal-organic frameworks (MOFs), constructed by discrete inorganic secondary building units (SBUs) and organic linkers, have emerged as a novel class of crystalline porous materials featuring high degrees of designability in porosity, structural topology, and host-guest interactions. [7][8][9] Typically, their pore size and shape, dimensionality, and active sites (e.g., appended functional groups, coordinatively unsaturated open metal sites) can be modulated judiciously via isoreticular chemistry. The past decade has witnessed significant advances in the synthesis of novel MOFs with adjustable physicochemical properties and their applications in molecule storage/separation, [10] catalysis, [11] drug delivery, [12] and chemical sensing. [13] However, MOFs intrinsically lack fluidity and thus processability. This issue severely impedes the scale-up production of MOF-based devices such as Metal-organic frameworks (MOFs) intrinsically lack fluidity and thus solution processability. Direct synthesis of MOFs exhibiting solution processability like polymers remains challenging but highly sought-after for multitudinous applications. Herein, a one-pot, surfactant-free, and scalable synthesis of highly stable MOF suspensions composed of exceptionally large (average area > 15 000 µm 2 ) NUS-8 nanosheets with variable functionalities and excellent solution processability is presented. This is achieved by adding capping molecules during the synthesis, and by judicious controls of precursor concentration and MOF nanosheet-solvent interactions. The resulting 2D NUS-8 nanosheets with variable functionalities exhibit excellent solution processability. As such, relevant monoliths, aero-and xerogels, and large-area textured films with a great homogeneity, controllable thickness, and appreciable mechanical properties can be facilely fabricated. Additionally, from both the molecular-and chip-level it is demonstrated that capacitive sensors integrated with NUS-8 films functionalized with different terminal groups exhibit distinguishable sensing behaviors toward acetone due to their disparate host-guest interactions. It is envisioned that this simple approach will greatly facilitate the integration of MOFs in miniaturized electronic devices and benefit their mass production.