Brain-targeted intranasal delivery of protein-based gene therapy for treatment of ischemic stroke.

Gene therapy using a protein-based CRISPR system in the brain has practical limitations due to current delivery systems, especially in the presence of arterial occlusion. To overcome these obstacles and improve stability, we designed a system for intranasal administration of gene therapy for the treatment of ischemic stroke. Nanoparticles containing the protein-based CRISPR/dCas9 system targeting were delivered intranasally to the brain in a mouse model of ischemic stroke.

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 (C ). This study demonstrates how this trade-off limitation can be overcome by replacing some electrode NPs with transparent tin oxide (SnO ) NPs. Although SnO NPs are non-capacitive, they provide effective paths for charge transport, which simultaneously increase the C and T of the manganese oxide (Mn O ) NP electrode from 11.

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.

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 CsPbA (A: Cl, Br, I) nanocrystals (NCs) with organic molecules (2,5-diphenyloxazole). The hybrid liquid scintillators, compared to state-of-the-art CsI and GdOS, demonstrate markedly highly competitive radioluminescence quantum yields under X-ray irradiation typically employed in diagnosis and treatment.

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.

L‑Deprenyl 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 anti‑leukemic activity, based on evidence that AML cells have an abnormally high amount of mitochondria and that somatic mutations can alter metabolic flux in cancer.

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.

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.

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

The supercapacitive properties of manganese oxide (MnO) 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 , become much slower than those of the planar and 2D-aligned electrode systems.

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.

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

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.

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.

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.

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%.