Towards Optical Information Recording: A Robust Visible-Light-Driven Molecular Photoswitch with the Ring-Closure Reaction Yield Exceeding 96.3 .

Diarylethene molecular photoswitches hold great fascination as optical information materials due to their unique bistability and exceptional reversible photoswitching properties. Conventional diarylethenes, however, rely on UV light for ring-closure reactions, typically with modest yields. For practical application, diarylethenes driven by visible lights are preferred but achieving high ring-closure reaction yield remains a significant challenge. Herein, we synthesized a novel all-visible-light-driven photoswitch, TPAP-DTE, by facilely endcapping the dithienylethene (DTE) core with triphenylamine phenyl (TPAP) groups. Owing to the electron-donating conjugation effect of TPAP, the open-form TPAP-DTE responds strongly to short-wavelength visible lights with considerable photocyclization quantum yields and molar absorption coefficient. Upon 405 nm visible-light irradiation, TPAP-DTE achieves a ring-closure reaction yield exceeding 96.3 % (confirmed by both nuclear magnetic resonance spectroscopy and high-performance liquid chromatography). Its ring-opening reaction yield is 100 % upon irradiation with long-wavelength visible light. TPAP-DTE could be regarded as a bidirectional "quasi"-quantitative conversion molecular switch. Furthermore, TPAP-DTE exhibits robust fatigue resistance over 100 full photoswitching cycles and great anti-aging property under 85 °C and 85 % humidity for at least 1000 h. Consequently, its rewritable QR-code, multilevel data storage, and anti-counterfeiting/encryption applications are successfully demonstrated exclusively using visible lights, positioning TPAP-DTE as a highly promising medium for information recording.

The Histone Methyltransferase Mixed Lineage Leukemia (MLL) 3 May Play a Potential Role on Clinical Dilated Cardiomyopathy.

Histone modifications play a critical role in the pathological processes of dilated cardiomyopathy (DCM). While the role and expression pattern of histone methyltransferases (HMTs), especially mixed lineage leukemia (MLL) families on DCM are unclear. To this end, twelve normal and fifteen DCM heart samples were included in the present study. A murine cardiac remodelling model was induced by transverse aortic constriction (TAC). Real-time PCR was performed to detect the expression levels of MLL families in the mouse and human left ventricles. The mRNA level of MLL3 was significantly increased in the mouse hearts treated by TAC surgery. Compared with normal hearts, higher mRNA and protein level of MLL3 was detected in the DCM hearts, and its expression level was closely associated with left ventricular end systolic diameter (LVEDD) and left ventricular ejection fraction (LVEF). However, the expression level of other MLL families (MLL, MLL2, MLL4, MLL5, SETD1A, and SETD1B) had no obvious change between control and DCM hearts or remodeled mouse hearts. Furthermore, the di-methylated histone H3 lysine 4 (H3K4me2) but not H3K4me3 was significantly increased in the DCM hearts. The protein levels of Smad3, GATA4, EGR1, which might regulate by MLL3, were remarkably elevated in the DCM hearts. Our hitherto unrecognized findings indicate that MLL3 has a potential role on pathological processes of DCM via regulating H3K4me2 and the expression of Smad3, GATA4, and EGR1.

EZH2 inhibits autophagic cell death of aortic vascular smooth muscle cells to affect aortic dissection.

Enhancer of zeste homolog 2 (EZH2), a methyltransferase that di- and tri-methylates lysine-27 of histone H3, largely functions as a transcriptional repressor, and plays a critical role in various kinds of cancers. Here we report a novel function of EZH2 in regulating autophagic cell death (ACD) of vascular smooth muscle cells (VSMCs) that affect aortic dissection (AD). Inhibition of EZH2 activity by UNC1999 or knockdown EZH2 resulted in VSMC loss, while overexpression of EZH2 facilitated VSMC growth, and these effects of EZH2 on VSMCs were independent of proliferation and apoptosis. Interestingly, more autophagic vacuoles and increased LC3II protein levels were identified in VSMCs with EZH2 inhibition or deficiency. Moreover, when compared with counterparts, chloroquine alone, or chloroquine with rapamycin treatment led to more LC3II accumulation in EZH2 inhibited or knockdown VSMCs, which indicated that EZH2 negatively regulated autophagosome formation. In conjunction to this, ATG5 and ATG7 protein levels were remarkably increased in EZH2 inhibited or deficient VSMCs, and ATG5 or ATG7 knockdown virtually rescued VSMC loss induced by EZH2 inhibition or knockdown. In addition, we found that the MEK-ERK1/2 signaling pathway, but not AMPKα, mTOR, or AKT pathway, is responsible for the impact of EZH2 on ACD of VSMCs. Additionally, the adverse effects of EZH2 inhibition or knockdown on VSMCs were largely reversed by PD98059, an inhibitor of MEK1. More importantly, decreased EZH2 expression levels in the aortic wall of patients with AD indicated its contribution to VSMC loss and AD occurrence. Overall, these findings revealed that EZH2 affects ACD of VSMCs and the pathologic process of AD via regulating ATG5 and ATG7 expression and MEK-ERK1/2 signaling. Our hitherto unrecognized findings indicate that EZH2 activation has therapeutic or preventive potential for AD.

Leucine-rich repeat neuronal protein 4 (LRRN4) potentially functions in dilated cardiomyopathy.

Leucine-rich repeat neuronal protein-4 (LRRN4 or NLRR4) has been identified as a new member of LRRN family, which is a group of proteins that contain leucine-rich repeat domains and functioned as regulators in a variety of pathologic processes including cardiac remodeling. However, the exact pattern of expression and function of LRRN4 in the human hearts is still unclear. In our study, the western blot test and real-time PCR were performed to detect the LRRN4 level in hearts of patients with dilated cardiomyopathy (DCM), ischemia heart disease (IHD) hearts respectively. Interestingly, the LRRN4 was highly expressed in donor hearts, but significantly reduced in hearts with DCM. While a comparable level of expression was detected in the IHD hearts when compared with donor hearts. Immunohistochemistry assay showed that LRRN4 was particularly expressed in cardiomyocytes and responsible for its decreased expression in the DCM hearts. Furthermore, we found LRRN4 was expressed in the ventricular cardiomyocytes of mice and apparently reduced after pressure overload treatment in the wild type mice. Therefore, our hitherto unrecognized findings provided the first evidence that the highly expressed LRRN4 is critical for maintaining morphology and function of heart. In addition to that, since its expression level decreased in DCM hearts but not IHD hearts, which indicated LRRN4 might be a therapeutic target clinically for DCM disease.

Aberrant Epicardial Adipose Tissue Extracellular Matrix Remodeling in Patients with Severe Ischemic Cardiomyopathy: Insight from Comparative Quantitative Proteomics.

There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio <0.8 or >1.2 fold and p < 0.05 in both repetitions) in EAT of ICM individuals. Gene ontology (GO) enrichment analysis revealed that cardiac structure and cellular metabolism were over-represented among these regulated proteins. The hypertrophic cardiomyopathy, adrenergic signaling in cardiomyocytes, extracellular matrix (ECM)-receptor interaction, phagosome, Glycolysis/Gluconeogenesis, and PPAR signaling pathway were highlighted by the KEGG PATHWAY analysis. More importantly, we found that the proteins responsible for extracellular matrix organization were dramatically increased in EAT of ICM patients. In addition, the picrosirius red (PSR) staining results showed that the collagen fiber content was prominently increased, which indicated the EAT of ICM individuals underwent extracellular matrix remodeling and ERK1/2 activation maybe responsible for these pathological changes partially.