Scope
Gallic acid (GA) is a dietary phenolic acid found in tea, red wine, and some plants. It exhibits anti‐oxidative and anti‐inflammatory activities. Recent studies have revealed that GA has ...beneficial effects against several cardiovascular diseases; however, whether GA attenuates pressure‐overload‐induced cardiac hypertrophy and the underlying mechanism remains unclear.
Methods and results
Primary cardiomyocyte hypertrophy is stimulated with angiotensin II (Ang II). Cardiac hypertrophic remodeling is induced in mice by transverse aortic constriction (TAC). Myocardial function is evaluated by echocardiographic and hemodynamic analyses, while cardiac tissues are analyzed by histological staining. It is observed that GA significantly decreases Ang II‐induced increases in cardiomyocyte size in vitro. Administration of GA in mice markedly improves TAC‐induced cardiac dysfunction and attenuates pathological changes, including cardiac myocyte hypertrophy, fibrosis, inflammation, and oxidative stress. Mechanistically, GA inhibits ULK1 and activates autophagy, which induces the degradation of EGFR, gp130, and calcineurin A, thereby inhibiting the downstream signaling cascades (AKT, ERK1/2, JAK2/STAT3, and NFATc1).
Conclusions
The results demonstrate for the first time that GA prevents myocardial hypertrophy and dysfunction via an autophagy‐dependent mechanism. Thus, GA represents a promising therapeutic candidate for treating cardiac hypertrophy and heart failure.
Gallic acid (GA), a type of dietary phenolic acid found in tea and other plants, prevents angiotensin II‐induced cardiomyocyte hypertrophy and pressure overload‐induced myocardial dysfunction. Mechanistically, GA enhances autophagy activation which promotes degradation of epidermal growth factor receptor, glycoprotein 130 and calcineurin A resulting in inhibition of downstream signaling cascades.
We discuss the de Sitter swampland and trans-Planckian censorship conjectures (TCC) from the entropy bound with quantum corrections, namely quantum version of Bousso's bound and energy conditions. We ...include the typical contributions from the entanglement entropy in quasi-de Sitter spacetime. The TCC is not much corrected, whereas the bounds on de Sitter swampland conjecture from energy conditions can be relaxed due to quantum corrections.
We discuss the possibility that accreting black hole systems can be sources for dark matter flux through several different mechanisms. We firstly discuss two types of systems‘: coronal thermal ...plasmas around supermassive black holes in active galactic nuclei (AGNs), and accretion disks of stellar-mass X-ray black hole binaries (BHBs). We explore how these black hole systems may produce keV light dark matter fluxes and find that the dark fluxes from those sources might be too weak to account for the current XENON1T excess. On the other hand, black holes can be good accelerators to accrete and boost heavy dark matter particles. If considering collisions or dark electromagnetism, those particles can then escape and reach the benchmark speed of 0.1c at the detector. We also extend the black hole mass region to primordial black holes (PBHs) and discuss the possibility of contributing to keV light dark flux via superradiance of PBHs.
Cobalt–nitrogen–carbon is hitherto considered as one of the most satisfactory alternatives to precious metal catalysts for oxygen electrocatalysts. However, precisely tuning the local coordination of ...Co sites and thus engineering d‐orbital electron configuration to optimize the binding energy of the intermediates remains a huge challenge. Herein, a robust electrostatic self‐assembly strategy is developed to engineer penta‐coordinated Co sites by introducing axial O ligands with atomic‐level precision to form CoN4O1 configurations on MXene nanosheets (CoN4‐O/MX). The optimized CoN4‐O/MX demonstrates outstanding bifunctional electrocatalytic performance with a small potential gap of 0.72 V, significantly outperforming the cobalt–nitrogen–carbon catalyst with plane‐symmetric CoN4 sites and precious metal counterparts. The Zn–air batteries integrated with CoN4‐O/MX provide an outstanding peak power density of 182.8 mW cm−2 and a long‐term cyclability for 250 h. Density functional theory calculations reveal that CoO coordination induces electronic delocalization to draw off partial electrons from the dz2 orbital, which forms unsaturated orbital filling and lifts the energy level, resulting in a stronger Lewis basicity to facilitate electron injection into the intermediate. The study presented here provides not only a novel methodology to achieve precise control of heteroatom coordination, but also a fundamental understanding about the structure–activity relationships of dz2 orbitals.
A robust electrostatic self‐assembly strategy is developed to engineer penta‐coordinated Co sites by introducing axial O ligands with atomic‐level precision to form CoN4O1 configurations. CoO coordination induces electronic delocalization to regulate Co 3d orbitals energy level and dz2 orbital occupancy, resulting in improved OH* intermediate activation abilities and outstanding ORR performance compared to cobalt–nitrogen–carbon with symmetric Co‐N4 sites.
We hypothesized that the differentiation processes of cardiac progenitor cell (CP) from first and second heart fields (FHF and SHF) may undergo the unique instructive gene regulatory networks or ...signaling pathways, and the precise SHF progression is contingent on the FHF signaling developmental cues.
We investigated how the intraorgan communications control sequential building of discrete anatomic regions of the heart at single-cell resolution.
By single-cell transcriptomic analysis of Nkx2-5 (NK2 homeobox 5) and Isl1 (ISL LIM homeobox 1) lineages at embryonic day 7.75, embryonic day 8.25, embryonic day 8.75, and embryonic day 9.25, we present a panoramic view of distinct CP differentiation hierarchies. Computational identifications of FHF- and SHF-CP descendants revealed that SHF differentiation toward cardiomyocytes underwent numerous step-like transitions, whereas earlier FHF progressed toward cardiomyocytes in a wave-like manner. Importantly, single-cell pairing analysis demonstrated that SHF-CPs were attracted to and expanded FHF-populated heart tube region through interlineage communications mediated by the chemotactic guidance (MIF macrophage migration inhibitory factor-CXCR2 C-X-C motif chemokine receptor 2). This finding was verified by pharmacological blockade of this chemotaxis in embryos manifesting limited SHF cell migration and contribution to the growth of the outflow tract and right ventricle but undetectable effects on the left ventricle or heart tube initiation. Genetic loss-of-function assay of Cxcr2 showed that the expression domain of CXCR4 was expanded predominantly at SHF. Furthermore, double knockout of Cxcr2/Cxcr4 exhibited defective SHF development, corroborating the redundant function. Mechanistically, NKX2-5 directly bound the Cxcr2 and Cxcr4 genomic loci and activated their transcription in SHF.
Collectively, we propose a model in which the chemotaxis-mediated intraorgan crosstalk spatiotemporally guides the successive process of positioning SHF-CP and promoting primary heart expansion and patterning upon FHF-derived heart tube initiation.
Atomically dispersed metal‐nitrogen‐carbon (M‐N‐C) catalysts have exhibited encouraging oxygen reduction reaction (ORR) activity. Nevertheless, the insufficient long‐term stability remains a ...widespread concern owing to the inevitable 2‐electron byproducts, H2O2. Here, we construct Co‐N‐Cr cross‐interfacial electron bridges (CIEBs) via the interfacial electronic coupling between Cr2O3 and Co‐N‐C, breaking the activity‐stability trade‐off. The partially occupied Cr 3d‐orbitals of Co‐N‐Cr CIEBs induce the electron rearrangement of CoN4 sites, lowering the Co‐OOH* antibonding orbital occupancy and accelerating the adsorption of intermediates. Consequently, the Co‐N‐Cr CIEBs suppress the two‐electron ORR process and approach the apex of Sabatier volcano plot for four‐electron pathway simultaneously. As a proof‐of‐concept, the Co‐N‐Cr CIEBs is synthesized by the molten salt template method, exhibiting dominant 4‐electron selectively and extremely low H2O2 yield confirmed by Damjanovic kinetic analysis. The Co‐N‐Cr CIEBs demonstrates impressive bifunctional oxygen catalytic activity (▵E=0.70 V) and breakthrough durability including 100 % current retention after 10 h continuous operation and cycling performance over 1500 h for Zn‐air battery. The hybrid interfacial configuration and the understanding of the electronic coupling mechanism reported here could shed new light on the design of superdurable M‐N‐C catalysts.
A cross‐interfacial electronic bridges (CIEBs) is constructed via interfacial electronic coupling between Cr2O3 and Co‐N‐C, breaking the trade‐off between activity and stability. The partially occupied Cr 3d‐orbitals of Co‐N‐Cr CIEBs induce the electron rearrangement of CoN4 sites, lowering the Co‐OOH* antibonding orbital occupancy and accelerating the adsorption of intermediates. Consequently, the Co‐N‐Cr CIEBs suppress the two‐electron ORR process and approach the apex of Sabatier volcano plot for four‐electron pathway simultaneously.
Atrial fibrillation (AF) is associated with inflammation and oxidative stress. Recently, we demonstrated that the chemokine‐receptor CXCR2 plays a critical role in the recruitment of ...monocytes/macrophages and the development of hypertension and cardiac remodelling. However, the role of CXCR2 in the pathogenesis of hypertensive AF remains unclear. AF was induced in Wistar‐Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) administered with the CXCR2 inhibitor SB225002. Atrial remodelling, pathological changes and electrophysiology were examined. Our results showed that the chemokine CXCL1 and its receptor CXCR2 were markedly increased in atrial tissue of SHRs compared with WKYs. The administration of SB225002 to SHRs significantly reduced the elevation of blood pressure, AF inducibility and duration, atrial remodelling, recruitment of macrophages, superoxide production and conduction abnormalities compared with vehicle treatment. The administration of SB225002 to SHRs also reversed pre‐existing AF development, atrial remodelling, inflammation and oxidative stress. These effects were associated with the inhibition of multiple signalling pathways, including TGF‐β1/Smad2/3, NF‐κB‐P65, NOX1, NOX2, Kir2.1, Kv1.5 and Cx43. In conclusion, this study provides new evidence that blocking CXCR2 prevents and reverses the development of AF in SHRs, and suggests that CXCR2 may be a potential therapeutic target for hypertensive AF.
A
bstract
We discuss a scenario that the dark matter in late time universe emerges as part of the holographic stress-energy tensor on the hypersurface in higher dimensional flat spacetime. Firstly we ...construct a toy model with a de Sitter hypersurface as the holographic screen in the flat bulk. After adding the baryonic matter on the screen, we assume that both of the dark matter and dark energy can be described by the Brown-York stress-energy tensor. From the Hamiltonian constraint equation in the flat bulk, we find an interesting relation between the dark matter and baryonic matter’s energy density parameters, by comparing with the Lambda cold dark matter parameterization. We further compare this holographic embedding of emergent dark matter with traditional braneworld scenario and present an alternative interpretation as the holographic universe. It can be reduced to our toy constraint in the late time universe, with the new parameterization of the Friedmann equation. We also comment on the possible connection with Verlinde’s emergent gravity, where the dark matter is treated as the elastic response of the baryonic matter on the de Sitter spacetime background. We show that from the holographic de Sitter model with elasticity, the Tully-Fisher relation and the dark matter distribution in the galaxy scale can be derived.
PDF
