The facile synthesis and optical waveguide properties of single-crystal 1,2,3,4,5-pentaphenyl-1,3-cyclopentadiene microrods.

Single-crystalline 1,2,3,4,5-pentaphenyl-1,3-cyclopentadiene (PPCP) microrods were prepared by a facile solution process. The PPCP microrods with smooth surfaces could absorb excitation light and propagate the photoluminescence (PL) emission. They showed excellent properties in the low optical loss of a single rod and feasible transfer between neighboring rods. Moreover, PPCP displayed typical aggregation-induced emission enhancement (AIEE) characteristics in the solution state.

Metal Ions Mediated Morphology and Phase Transformation of Chalcogenide Semiconductor: From CuClSe2 Microribbon to CuSe Nanosheet.

Foreign ions are of significant importance in controlling and modulating the morphology of semiconductor nanocrystals during the colloidal synthesis process. Herein, we demonstrate the potential of foreign metal ions to simultaneously control the morphology and crystal phase of chalcogenide semiconductors. The results indicate that the introduction of Al(3+) ions can induce the structural transformation from monoclinic CuClSe2 microribbons (MRs) to klockmannite CuSe nanosheets (NSs) and the growth of large-sized CuSe NSs. The as-prepared micrometer-sized CuSe NSs exhibit a high-conducting behavior, long-term durability, and environment stability. The novel properties enable CuSe NSs to open up a bright prospect for printable electrical interconnects and flexible electronic devices.

In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice.

RATIONALE: During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring protein, junctophilin-2. MicroRNA (miR)-24, a junctophilin-2 suppressing miR, is upregulated in hypertrophied and failing cardiomyocytes. OBJECTIVE: To test whether miR-24 suppression can protect the structural and functional integrity of L-type Ca(2+) channel-ryanodine receptor signaling in hypertrophied cardiomyocytes. METHODS AND RESULTS: In vivo silencing of miR-24 by a specific antagomir in an aorta-constricted mouse model effectively prevented the degradation of heart contraction, but not ventricular hypertrophy. Electrophysiology and confocal imaging studies showed that antagomir treatment prevented the decreases in L-type Ca(2+) channel-ryanodine receptor signaling fidelity/efficiency and whole-cell Ca(2+) transients. Further studies showed that antagomir treatment stabilized junctophilin-2 expression and protected the ultrastructure of T-tubule-sarcoplasmic reticulum junctions from disruption. CONCLUSIONS: MiR-24 suppression prevented the transition from compensated hypertrophy to decompensated hypertrophy, providing a potential strategy for early treatment against heart failure.

Preparation and Optical Waveguiding Property of Single-Crystal Organic NPB Microsheets.

2D microstructures of N,N'-diphenyl-N,N'-bis(1-naphthyl)-1,1'-biphenyl-4,4'-di-amine (NPB) have been prepared by a facile solution method and fully characterized. The as-prepared NPB microsheets have well-defined shapes and very smooth surfaces, and are ideal building blocks for 2D optical waveguides. The results indicate that the optic losses within NPB microsheets are closely related to the direction of propagation, and the shape of microsheets can change the direction of waveguiding light. Such 2D optical waveguides may have potential applications in future miniaturized light-based circuits serve as interconnectors different from 1 D optical waveguides.

Mir-24 regulates junctophilin-2 expression in cardiomyocytes.

RATIONALE: Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as a major mechanism underlying the defective E-C coupling. However, the regulatory mechanism of JP2 remains unknown. OBJECTIVE: To determine whether microRNAs regulate JP2 expression. METHODS AND RESULTS: Bioinformatic analysis predicted 2 potential binding sites of miR-24 in the 3'-untranslated regions of JP2 mRNA. Luciferase assays confirmed that miR-24 suppressed JP2 expression by binding to either of these sites. In the aortic stenosis model, miR-24 was upregulated in failing cardiomyocytes. Adenovirus-directed overexpression of miR-24 in cardiomyocytes decreased JP2 expression and reduced Ca(2+) transient amplitude and E-C coupling gain. CONCLUSIONS: MiR-24-mediated suppression of JP2 expression provides a novel molecular mechanism for E-C coupling regulation in heart cells and suggests a new target against heart failure.

Preparation of cocrystal nanofibres of cobalt octaethylporphyrin and tetracyanoquinodimethane with good photoresponse.

Cocrystal nanofibres of cobalt octaethylporphyrin and tetracyanoquinodimethane were prepared by a facile solution method and fully characterized by SEM, AFM, XRD, Raman, EDX, and UV-vis-NIR. The as-prepared cocrystal nanofibres had smooth surfaces and uniform dimension. When incorporated into prototype devices, they exhibited good photoresponse at ambient conditions. Additionally, the phototransistor characteristics with a maximum I(on)/I(off) ratio of -460 was demonstrated. The facile synthesis and good photoresponse may boost the potential applications of cocrystal-based nanostructures in future miniaturized devices.

FGF17 protects cerebral ischemia reperfusion-induced blood-brain barrier disruption via FGF receptor 3-mediated PI3K/AKT signaling pathway.

Maintaining blood-brain barrier (BBB) integrity is critical components of therapeutic approach for ischemic stroke. Fibroblast growth factor 17 (FGF17), a member of FGF8 superfamily, exhibits the strongest expression throughout the wall of all major arteries during development. However, its molecular action and potential protective role on brain endothelial cells after stroke remains unclear. Here, we observed reduced levels of FGF17 in the serum of patients with ischemic stroke, as well as in the brains of mice subjected to middle cerebral artery occlusion (MCAO) injury and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced brain microvascular endothelial cells (bEnd.3) cells. Moreover, treatment with exogenous recombinant human FGF17 (rhFGF17) decreased infarct volume, improved neurological deficits, reduced Evans Blue leakage and upregulated the expression of tight junctions in MCAO-injured mice. Meanwhile, rhFGF17 increased cell viability, enhanced trans-endothelial electrical resistance, reduced sodium fluorescein leakage, and alleviated reactive oxygen species (ROS) generation in OGD/R-induced bEnd.3 cells. Mechanistically, the treatment with rhFGF17 resulted in nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation and upregulation of heme oxygenase-1 (HO-1) expression. Additionally, based on in-vivo and in-vitro research, rhFGF17 exerted protective effects against ischemia/reperfusion (I/R) -induced BBB disruption and endothelial cell apoptosis through the activation of the FGF receptor 3/PI3K/AKT signaling pathway. Overall, our findings indicated that FGF17 may hold promise as a novel therapeutic strategy for ischemic stroke patients.

Necroptosis signaling and mitochondrial dysfunction cross-talking facilitate cell death mediated by chelerythrine in glioma.

Glioma is the most common primary malignant brain tumor with poor survival and limited therapeutic options. Chelerythrine (CHE), a natural benzophenanthridine alkaloid, has been reported to exhibit the anti-tumor effects in a variety of cancer cells. However, the molecular target and the signaling process of CHE in glioma remain elusive. Here we investigated the underlying mechanisms of CHE in glioma cell lines and glioma xenograft mice model. Our results found that CHE-induced cell death is associated with RIP1/RIP3-dependent necroptosis rather than apoptotic cell death in glioma cells at the early time. Mechanism investigation revealed the cross-talking between necroptosis and mitochondria dysfunction that CHE triggered generation of mitochondrial ROS, mitochondrial depolarization, reduction of ATP level and mitochondrial fragmentation, which was the important trigger for RIP1-dependent necroptosis activation. Meanwhile, PINK1 and parkin-dependent mitophagy promoted clearance of impaired mitochondria in CHE-incubated glioma cells, and inhibition of mitophagy with CQ selectively enhanced CHE-induced necroptosis. Furthermore, early cytosolic calcium from the influx of extracellular Ca2+ induced by CHE acted as important "priming signals" for impairment of mitochondrial dysfunction and necroptosis. Suppression of mitochondrial ROS contributed to interrupting positive feedback between mitochondrial damage and RIPK1/RIPK3 necrosome. Lastly, subcutaneous tumor growth in U87 xenograft was suppressed by CHE without significant body weight loss and multi-organ toxicities. In summary, the present study helped to elucidate necroptosis was induced by CHE via mtROS-mediated formation of the RIP1-RIP3-Drp1 complex that promoted Drp1 mitochondrial translocation to enhance necroptosis. Our findings indicated that CHE could potentially be further developed as a novel therapeutic strategy for treatment of glioma.

Investigation of transport properties of coronene·TCNQ cocrystal microrods with coronene microrods and TCNQ microsheets.

Coronene·TCNQ cocrystal microrods, coronene microrods, and TCNQ microsheets were constructed by a drop-casting method. Prototype devices were fabricated and their field-effect-transistor (FET) performances were investigated. It is found that coronene·TCNQ microrods had exhibited an n-type characteristic and showed better FET performances than TCNQ microsheets.

Aerosol-jet printing of nanowire networks of zinc octaethylporphyrin and its application in flexible photodetectors.

Nanowire networks of zinc octaethylporphyrin (ZnOEP) were printed using an aerosol-jet printer on a poly(ethylene terephthalate) (PET) flexible substrate. The prototype photodetector based on the as-printed network exhibited high photosensitivity, fast photoresponse, and excellent mechanical stability.

Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure.

AIMS: Chronic heart failure is a complex clinical syndrome with impaired myocardial contractility. In failing cardiomyocytes, decreased signalling efficiency between the L-type Ca(2+) channels (LCCs) in the plasma membrane (including transverse tubules, TTs) and the ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) underlies the defective excitation-contraction (E-C) coupling. It is therefore intriguing to know how the LCC-RyR signalling apparatus is remodelled in human heart failure. METHODS AND RESULTS: Stereological analysis of transmission electron microscopic images showed that the volume densities and the surface areas of TTs and junctional SRs were both decreased in heart failure specimens of dilated cardiomyopathy (DCM) and ischaemic cardiomyopathy (ICM). The TT-SR junctions were reduced by ~60%, with the remaining displaced from the Z-line areas. Moreover, the spatial span of individual TT-SR junctions was reduced by ~17% in both DCM and ICM tissues. In accordance with these remodelling, junctophilin-2 (JP2), a structural protein anchoring SRs to TTs, was down-regulated, and miR-24, a microRNA that suppresses JP2 expression, was up-regulated in both heart failure tissues. CONCLUSION: Human heart failure of distinct causes shared similar physical uncoupling between TTs and SRs, which appeared attributable to the reduced expression of JP2 and increased expression of miR-24. Therapeutic strategy against JP2 down-regulation would be expected to protect patients from cardiac E-C uncoupling.

Ultrastructural remodelling of Ca(2+) signalling apparatus in failing heart cells.

AIMS: The contraction of a heart cell is controlled by Ca(2+)-induced Ca(2+) release between L-type Ca(2+) channels (LCCs) in the cell membrane/T-tubules (TTs) and ryanodine receptors (RyRs) in the junctional sarcoplasmic reticulum (SR). During heart failure, LCC-RyR signalling becomes defective. The purpose of the present study was to reveal the ultrastructural mechanism underlying the defective LCC-RyR signalling and contractility. METHODS AND RESULTS: In rat models of heart failure produced by transverse aortic constriction surgery, stereological analysis of transmission electron microscopic images showed that the volume density and the surface area of junctional SRs and those of SR-coupled TTs were both decreased in failing heart cells. The TT-SR junctions were displaced or missing from the Z-line areas. Moreover, the spatial span of individual TT-SR junctions was markedly reduced in failing heart cells. Numerical simulation and junctophilin-2 knockdown experiments demonstrated that the decrease in junction size (and thereby the constitutive LCC and RyR numbers) led to a scattered delay of Ca(2+) release activation. CONCLUSIONS: The shrinking and eventual absence of TT-SR junctions are important mechanisms underlying the desynchronized and inhomogeneous Ca(2+) release and the decreased contractile strength in heart failure. Maintaining the nanoscopic integrity of TT-SR junctions thus represents a therapeutic strategy against heart failure and related cardiomyopathies.