Computed Tomography Perfusion Alberta Stroke Program Early Computed Tomography Score Is Associated with Hemorrhagic Transformation after Acute Cardioembolic Stroke

Alberta Stroke Program Early Computed Tomography (CT) score (ASPECTS) has been applied to CT perfusion (CTP) with good interrater agreement to predict early ischemic stroke, and it can be useful in decision making in acute ischemic stroke. The aim of the present study was to assess the predictive value of CTP ASPECTS of hemorrhagic transformation (HT) in acute cardioembolic stroke. This is a single-enter, retrospective study. All patients hospitalized with acute cardioembolic stroke from January 2008 to September 2013 were included. ASPECTS of baseline non-contrast CT, CTP maps of cerebral blood volume (CBV), cerebral blood flow, and mean transit time were collected from 52 consecutive patients with less than 12-h anterior circulation ischemic stroke. MRI scan was performed within 72 h of symptom onset after index stroke including T2*-weighted gradient echo to identify HT. For bleeding risk assessment, CTP and diffusion-weighted imaging ASPECTS were categorized into 0–7 or 8–10. Baseline characteristics, ASPCETS scores and HT were compared. Eighteen (34.6%) patients had HT and four (7.7%) developed symptomatic HT. On univariate analysis, the proportion of patients with CBV-ASPECTS 0–7 was significantly higher in HT patients as compared to patients without HT (44 versus 9%, P = 0.005). CBV ASPECTS 0–7 remained independent prognostic factors for HT after adjustment for clinical baseline variables. CBV ASPECTS could be of value to predict HT risk after acute cardioembolic stroke and may be a quick risk assessment approach before reperfusion therapy

Hyperexpressed netrin-1promoted neural stem cells migration in mice after focal cerebral ischemia

Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explore whether NT-1 can be steadily overexpressed by AAV and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with adeno-associated virus carrying NT-1 gene (AAV-NT-1). Mice underwent 60 minutes of middle cerebral artery occlusion one week after injection. We found that NT-1 mainly expressed in neuron and astrocyte, and the expression level of NT-1 significantly increased one week after AAV-NT-1 gene transfer and lasted for 28 days, even after tMCAO as well (p＜0.05). Immunohistochemistry results showed that the number of neural stem cells was greatly increased in the SVZ region of AAV-NT-1-transduced mice compared with control mice. Our study showed that overexpressed NT-1 promoted neural stem cells migration from SVZ, this result suggested that NT-1 is a promising factor for repairing and remodeling after focal cerebral ischemia

Design of a Modular DNA Triangular-Prism Sensor Enabling Ratiometric and Multiplexed Biomolecule Detection on a Single Microbead

DNA nanostructures have emerged as powerful and versatile building blocks for the construction of programmable nanoscale structures and functional sensors for biomarker detection, disease diagnostics, and therapy. Here we integrated multiple sensing modules into a single DNA three-dimensional (3D) nanoarchitecture with a triangular-prism (TP) structure for ratiometric and multiplexed biomolecule detection on a single microbead. In our design, the complementary hybridization of three clip sequences formed TP nanoassemblies in which the six single-strand regions in the top and bottom faces act as binding sites for different sensing modules, including an anchor module, reference sequence module, and capture sequence module. The multifunctional modular TP nanostructures were thus exploited for ratiometric and multiplexed biomolecule detection on microbeads. Microbead imaging demonstrated that, after ratiometric self-calibration analysis, the imaging deviations resulting from uneven fluorescence intensity distribution and differing probe concentrations were greatly reduced. The rigid nanostructure also conferred the TP as a framework for geometric positioning of different capture sequences. The inclusion of multiple targets led to the formation of sandwich hybridization structures that gave a readily detectable optical response at different fluorescence channels and distinct fingerprint-like pattern arrays. This approach allowed us to discriminate multiplexed biomolecule targets in a simple and efficient fashion. In this module-designed strategy, the diversity of the controlled DNA assembly coupled with the geometrically well-defined rigid nanostructures of the TP assembly provides a flexible and reliable biosensing approach that shows great promise for biomedical applications

Programmable Self-Assembly of DNA–Protein Hybrid Hydrogel for Enzyme Encapsulation with Enhanced Biological Stability

A DNA–protein hybrid hydrogel was constructed based on a programmable assembly approach, which served as a biomimetic physiologic matrix for efficient enzyme encapsulation. A dsDNA building block tailored with precise biotin residues was fabricated based on supersandwich hybridization, and then the addition of streptavidin triggered the formation of the DNA–protein hybrid hydrogel. The biocompatible hydrogel, which formed a flower-like porous structure that was 6.7 ± 2.1 μm in size, served as a reservoir system for enzyme encapsulation. Alcohol oxidase (AOx), which served as a representative enzyme, was encapsulated in the hybrid hydrogel using a synchronous assembly approach. The enzyme-encapsulated hydrogel was utilized to extend the duration time for ethanol removal in serum plasma and the enzyme retained 78% activity after incubation with human serum for 24 h. The DNA–protein hybrid hydrogel can mediate the intact immobilization on a streptavidin-modified and positively charged substrate, which is very beneficial to solid-phase biosensing applications. The hydrogel-encapsulated enzyme exhibited improved stability in the presence of various denaturants. For example, the encapsulated enzyme retained 60% activity after incubation at 55 °C for 30 min. The encapsulated enzyme also retains its total activity after five freeze–thaw cycles and even suspended in solution containing organic solvents