Overcoming the Trade-Off between Optical Transmittance and Areal Capacitance of Transparent Supercapacitors for Practical Application.

It is substantially challenging for transition metal oxide nanoparticle (NP)-based electrodes for supercapacitors to achieve high transparency and large capacity simultaneously due to the inherent trade-off between optical transmittance (T) and areal capacitance (CA ). This study demonstrates how this trade-off limitation can be overcome by replacing some electrode NPs with transparent tin oxide (SnO2 ) NPs. Although SnO2 NPs are non-capacitive, they provide effective paths for charge transport, which simultaneously increase the CA and T550nm of the manganese oxide (Mn3 O4 ) NP electrode from 11.7 to 13.4 mF cm-2 and 82.1% to 87.4%, respectively, when 25 wt% of Mn3 O4 are replaced by SnO2 . The obtained CA values at a given T are higher than those of the transparent electrodes previously reported. An energy storage window fabricated using the mixed-NP electrodes exhibits the highest energy density among transparent supercapacitors previously reported. The improved energy density enables the window to operate various electronic devices for a considerable amount of time, demonstrating its applicability in constructing a reliable and space-efficient building-integrated power supply system.

ABL001, a Bispecific Antibody Targeting VEGF and DLL4, with Chemotherapy, Synergistically Inhibits Tumor Progression in Xenograft Models.

Delta-like-ligand 4 (DLL4) is a promising target to augment the effects of VEGF inhibitors. A simultaneous blockade of VEGF/VEGFR and DLL4/Notch signaling pathways leads to more potent anti-cancer effects by synergistic anti-angiogenic mechanisms in xenograft models. A bispecific antibody targeting VEGF and DLL4 (ABL001/NOV1501/TR009) demonstrates more potent in vitro and in vivo biological activity compared to VEGF or DLL4 targeting monoclonal antibodies alone and is currently being evaluated in a phase 1 clinical study of heavy chemotherapy or targeted therapy pre-treated cancer patients (ClinicalTrials.gov Identifier: NCT03292783). However, the effects of a combination of ABL001 and chemotherapy on tumor vessels and tumors are not known. Hence, the effects of ABL001, with or without paclitaxel and irinotecan were evaluated in human gastric or colon cancer xenograft models. The combination treatment synergistically inhibited tumor progression compared to each monotherapy. More tumor vessel regression and apoptotic tumor cell induction were observed in tumors treated with the combination therapy, which might be due to tumor vessel normalization. Overall, these findings suggest that the combination therapy of ABL001 with paclitaxel or irinotecan would be a better clinical strategy for the treatment of cancer patients.

Non-cell autonomous modulation of tyrosine hydroxylase by HMGB1 released from astrocytes in an acute MPTP-induced Parkinsonian mouse model.

High-mobility group box 1 (HMGB1) is actively secreted from inflammatory cells and acts via a non-cell-autonomous mechanism to play an important role in mediating cell proliferation and migration. The HMGB1-RAGE (receptor for advanced glycation end products) axis upregulates tyrosine hydroxylase (TH) expression in response to extracellular insults in dopaminergic neurons in vitro, but little is known about HMGB1 in modulation of dopaminergic neurons in vivo. Here, using immunohistochemistry, we show that HMGB1 and RAGE expression are higher in the nigral area of MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a toxin-induced Parkinsonian mouse model, compared with saline-treated controls. HMGB1 was predominantly localized to astrocytes and may affect neighboring dopaminergic neurons in the MPTP mouse model, owing to co-localization of RAGE in these TH-positive cells. In addition, MPTP induced a decrease in TH expression, an effect that was potentiated by inhibition of c-Jun N-terminal kinase (JNK) or RAGE. Moreover, stereotaxic injection of recombinant HMGB1 attenuated the MPTP-induced reduction of TH in a Parkinsonian mouse model. Collectively, our results suggest that an increase of HMGB1, released from astrocytes, upregulates TH expression in an acute MPTP-induced Parkinsonian mouse model, thereby maintaining dopaminergic neuronal functions.

Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation.

The derangement of tyrosine hydroxylase (TH) activity reduces dopamine synthesis and is implicated in the pathogenesis of Parkinson's disease. However, the extracellular modulator and intracellular regulatory mechanisms of TH have yet to be identified. Recently, high-mobility group box 1 (HMGB1) was reported to be actively secreted from glial cells and is regarded as a mediator of dopaminergic neuronal loss. However, the mechanism for how HMGB1 affects TH expression, particularly through the receptor for advanced glycation endproducts (RAGE), has not yet been investigated. We found that recombinant HMGB1 (rHMGB1) upregulates TH mRNA expression via simultaneous activation of JNK phosphorylation, and this induction of TH expression is blocked by inhibitors of RAGE and JNK. To investigate how TH expression levels change through the HMGB1-RAGE axis as a result of MPP+ toxicity, we co-treated SN4741 dopaminergic cells with MPP+ and rHMGB1. rHMGB1 blocked the reduction of TH mRNA following MPP+ treatment without altering cell survival rates. Our results suggest that HMGB1 upregulates TH expression to maintain dopaminergic neuronal function via activating RAGE, which is dependent on JNK phosphorylation.

Coaxial RuO2-ITO nanopillars for transparent supercapacitor application.

Supercapacitive properties of ruthenium oxide (RuO2) nanoparticles electrodeposited onto the indium tin oxide (ITO) nanopillars were investigated. Compared to conventional planar current collectors, this coaxially nanostructured current collector-electrode system can provide increased contact for efficient charge transport, and the internanopillar spacing allows easy access of electrolyte ions. The morphological and electrochemical properties depended on the thickness of the RuO2 layers, i.e., the number of electrodeposition cycles. A maximum specific capacitance, Csp, of 1235 F/g at a scan rate of 50 mV/s was achieved for the 30-cycle deposited RuO2-ITO nanopillars. The other capacitive properties such as electrochemical reversibility and Csp retention at high scan rates also improved greatly.

Preparation of superhydrophobic, long-neck vase-like polymer surfaces.

Polymer surfaces comprising nanopillars with various geometries were prepared by nanoimprinting the surface using anodic aluminium oxide templates. In particular, a simple fabrication method for long-neck vase-like stepped nanopillars was established, and the surface showed considerable enhancement in the water contact angle, for example from 95.7° to 150.6° for the polystyrene surface. This enhanced hydrophobicity could be explained by the desirable reduction in the area of the solid-liquid interface and reduced sticking between the nanopillars.

Hybridisation of perovskite nanocrystals with organic molecules for highly efficient liquid scintillators.

Compared with solid scintillators, liquid scintillators have limited capability in dosimetry and radiography due to their relatively low light yields. Here, we report a new generation of highly efficient and low-cost liquid scintillators constructed by surface hybridisation of colloidal metal halide perovskite CsPbA3 (A: Cl, Br, I) nanocrystals (NCs) with organic molecules (2,5-diphenyloxazole). The hybrid liquid scintillators, compared to state-of-the-art CsI and Gd2O2S, demonstrate markedly highly competitive radioluminescence quantum yields under X-ray irradiation typically employed in diagnosis and treatment. Experimental and theoretical analyses suggest that the enhanced quantum yield is associated with X-ray photon-induced charge transfer from the organic molecules to the NCs. High-resolution X-ray imaging is demonstrated using a hybrid CsPbBr3 NC-based liquid scintillator. The novel X-ray scintillation mechanism in our hybrid scintillators could be extended to enhance the quantum yield of various types of scintillators, enabling low-dose radiation detection in various fields, including fundamental science and imaging.

L­Deprenyl exerts cytotoxicity towards acute myeloid leukemia through inhibition of mitochondrial respiration.

The identification of large numbers of genetic mutations in immature myeloid cells has made it difficult to identify specific targets for acute myeloid leukemia (AML) therapy. Although current pharmacological targets for controlling cancer are focused on identifying genetic mutations, it is hard to develop the specific drugs to achieve complete remission due to complex and variable genetic mutations. To overcome the failure of the genetic mutation theory, the present study targeted mitochondrial metabolism as a strategy for inducing anti­leukemic activity, based on evidence that AML cells have an abnormally high amount of mitochondria and that somatic mutations can alter metabolic flux in cancer. It was found that L­deprenyl, which is clinically available for the treatment of Parkinson's disease, exerts anti­mitochondria activity in KG­1α cells, as assessed by detection of oxygen consumption rate (OCR) and extracellular acidification (ECAR) using XF analyzer, respectively. Using a luciferase assay for detecting adenosine triphosphate (ATP) content, it was found that suppression of mitochondrial activity led to ATP depletion and was associated with potent cytotoxic activity. L­deprenyl is known to target monoamine oxidase­B (MAO­B) on the outer membrane of mitochondria, therefore, the activity of MAO­A and ­B was measured based on the fluorometric detection of H2O2 produced by the enzyme reaction. Notably, MAO­A and -B activity was low in AML cells and the present findings suggested that the anticancer effect of L­deprenyl was independent of MAO­B. Change of mitochondrial respiration­ and glycolysis­related gene expression levels were measured by reverse transcription­quantitative polymerase chain reaction. Consistent with the aforementioned results, treatment with L­deprenyl reduced the mRNA level of mitochondrial respiration­ and glycolysis­related genes. Collectively, the present results identify L­deprenyl as a novel candidate for the treatment of AML through inhibition of mitochondrial respiration.

Retarded saturation of the areal capacitance using 3D-aligned MnO2 thin film nanostructures as a supercapacitor electrode.

The supercapacitive properties of manganese oxide (MnO2) thin films electrodeposited on three-dimensionally (3D) aligned inverse-opal nickel nanostructures are investigated. Compared to conventional planar or two-dimensionally (2D) aligned nanostructures, 3D-aligned nanostructures can provide considerably increased and controllable contacts between the electrode and electrolyte. As a result, saturation of the areal capacitance with the electrode thickness and associated decrease of the specific capacitance, C sp , become much slower than those of the planar and 2D-aligned electrode systems. While, for planar MnO2 electrodes, the C sp of a 60-cycle electrodeposited electrode is only the half of the 10-cycle electrodeposited one, the value of the 3D-nanostructured electrode remains unchanged under the same condition. The maximum C sp value of 864 F g-1, and C sp retention of 87.7% after 5000 cycles of galvanostatic charge-discharge are obtained. The voltammetric response is also improved significantly and the C sp measured at 200 mV s-1 retains 71.7% of the value measured at 10 mV s-1. More quantitative analysis on the effect of this 3D-aligned nanostructuring is also performed using a deconvolution of the capacitive elements in the total capacitance of the electrodes.

Supercapacitive Properties of 3D-Arrayed Polyaniline Hollow Nanospheres Encaging RuO2 Nanoparticles.

A major limitation of polyaniline (PANi) electrodes for supercapacitors is the slow rate of ion transport during redox reactions and the resultant easy saturation of areal capacitance with film thickness. In this study, three-dimensionally (3D)-arrayed PANi nanospheres with highly roughened surface nanomorphology were fabricated to overcome this limitation. A hierarchical nanostructure was obtained by polymerizing aniline monomers on a template of 3D-arrayed polystyrene (PS) nanospheres and appropriate oxidative acid doping. The structure provided dramatically increased surface area and porosity that led to the efficient diffusion of ions. Thus, the specific capacitance (Csp) reached 1570 F g-1, thereby approaching a theoretical capacitance of PANi. In addition, the retention at a high scan rate of 100 mV s-1 was 77.6% of the Csp at a scan rate of 10 mV s-1. Furthermore, 3D-arrayed hollow PANi (H-PANi) nanospheres could be obtained by dissolving the inner PS part of the PS/PANi core/shell nanospheres with tetrahydrofuran. The ruthenium oxide (RuO2) nanoparticles (NPs) were also encaged in the H-PANi nanospheres by embedding RuO2 NPs on the PS nanospheres prior to polymerization of PANi. The combination of the two active electrode materials indicated synergetic effects. The areal capacitance of the RuO2-encaged PANi electrode was significantly larger than that of the RuO2-free PANi electrode and could be controlled by varying the amount of encaged RuO2 nanoparticles. The encagement could also solve the problem of detachment of RuO2 electrodes from the current collector. The effects of the nanostructuring and RuO2 encagement were also quantitatively analyzed by deconvoluting the total capacitance into the surface capacitive and insertion elements.

An Aptamer-Based Electrochemical Sensor That Can Distinguish Influenza Virus Subtype H1 from H5.

The surface protein hemagglutinin (HA) mediates the attachment of influenza virus to host cells containing sialic acid and thus facilitates viral infection. Therefore, HA is considered as a good target for the development of diagnostic tools for influenza virus. Previously, we reported the isolation of single-stranded aptamers that can distinguish influenza subtype H1 from H5. In this study, we describe a method for the selective electrical detection of H1 using the isolated aptamer as a molecular probe. After immobilization of the aptamer on Si wafer, enzyme-linked immunosorbent assay (ELISA) and field emission scanning electron microscopy (FE-SEM) showed that the immobilized aptamer bound specifically to the H1 subtype but not to the H5 subtype. Assessment by cyclic voltammetry (CV) also demonstrated that the immobilized aptamer on the indium thin oxide-coated surface was specifically bound to the H1 subtype only, which was consistent with the ELISA and FE-SEM results. Further measurement of CV using various amounts of H1 subtype provided the detection limit of the immobilized aptamer, which showed that a nanomolar scale of target protein was sufficient to produce the signal. These results indicated that the selected aptamer can be an effective probe for distinguishing the subtypes of influenza viruses by monitoring current changes.

A High-fat Diet Induces a Loss of Midbrain Dopaminergic Neuronal Function That Underlies Motor Abnormalities.

Movement defects in obesity are associated with peripheral muscle defects, arthritis, and dysfunction of motor control by the brain. Although movement functionality is negatively correlated with obesity, the brain regions and downstream signaling pathways associated with movement defects in obesity are unclear. A dopaminergic neuronal pathway from the substantia nigra (SN) to the striatum is responsible for regulating grip strength and motor initiation through tyrosine hydroxylase (TH) activity-dependent dopamine release. We found that mice fed a high-fat diet exhibited decreased movement in open-field tests and an increase in missteps in a vertical grid test compared with normally fed mice. This motor abnormality was associated with a significant reduction of TH in the SN and striatum. We further found that phosphorylation of c-Jun N-terminal kinase (JNK), which modulates TH expression in the SN and striatum, was decreased under excess-energy conditions. Our findings suggest that high calorie intake impairs motor function through JNK-dependent dysregulation of TH in the SN and striatum.

Effective surface oxidation of polymer replica molds for nanoimprint lithography.

In nanoimprint lithography, a surface oxidation process is needed to produce an effective poly(dimethylsiloxane) coating that can be used as an anti-adhesive surface of template molds. However, the conventional photooxidation technique or acidic oxidative treatment cannot be easily applied to polymer molds with nanostructures since surface etching by UV radiation or strong acids significantly damages the surface nanostructures in a short space of time. In this study, we developed a basic oxidative treatment method and consequently, an effective generation of hydroxyl groups on a nanostructured surface of polymer replica molds. The surface morphologies and water contact angles of the polymer molds indicate that this new method is relatively nondestructive and more efficient than conventional oxidation treatments.

Purification, structural characterization, and antioxidant activity of antioxidant substance from the red seaweed Gloiopeltis tenax.

An antioxidant substance (AOS) obtained from an enzymatic extract of the red seaweed Gloiopeltis tenax was purified by DEAE-Sephadex CL-6B and Sephadex G-100 column chromatography. The purification yield of AOS was 14.3%. The AOS predominantly contained fucose, mannose, and galactose but also contained a sulfate group. The structure of AOS was investigated by periodate oxidation, desulfation, Fourier transform-infrared spectroscopy, and nuclear magnetic resonance spectroscopy. AOS was mainly composed of alternating units of beta-D-Glc(1 --> 2)alpha-D-Man(1 --> 4)beta-D-Gal(1 --> 4)alpha-D-Man(1 --> 4)beta-D-Gal alpha-D-Man (1 --> 4) beta-D-Glc (or Xyl)- and branched linkage of alpha-D-Man(1 --> 3) alpha-D-Fuc. In addition, the fucose residues were shown to be 2-O- and 4-O-sulfated and, therefore, were either terminal or 3-linked. The antioxidative activity of AOS was measured using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and the beta-carotene-linoleate assay systems and was compared with those of butylated hydroxytoluene and ascorbic acid (AscA). The results showed that AOS exhibited higher antioxidative activity than AscA in the DPPH assay model and in the beta-carotene-linoleate assay system at all of the four concentration levels tested (from 50 to 200 microg/mL). These results suggested that AOS from the red seaweed G. tenax is an efficient novel antioxidant.