Pro-inflammatory S100A9 protein as a robust biomarker differentiating early stages of cognitive impairment in Alzheimer’s Diseased

Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ1−42and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer’s disease (MCI-AD), Alzheimer’s disease (AD), and vascular dementia (VaD) patients. ELISA, dot-blotting, and electrochemical impedance spectroscopy were used as research methods. The S100A9 and Aβ1−42 levels correlated with each other: their CSF content decreased already at the SMCI stage and declined further under MCIAD, AD, and VaD conditions. Immunohistochemical analysis also revealed involvement of both Aβ1−42 and S100A9 in the amyloid-neuroinflammatory cascade already during SMCI. Tau proteins were not yet altered in SMCI; however their contents increased during MCI-AD and AD, diagnosing later dementia stages. Thus, four biomarkers together, reflecting different underlying pathological causes, can accurately differentiate dementia progression and also distinguish AD from Va

The first prospective application of AIGS real-time fluorescence PCR in precise diagnosis and treatment of meningioma: Case report

BackgroundThe emergence of the new WHO classification standard in 2021 incorporated molecular characteristics into the diagnosis system for meningiomas, making the diagnosis and treatment of meningiomas enter the molecular era.Recent findingsAt present, there are still some problems in the clinical molecular detection of meningioma, such as low attention, excessive detection, and a long cycle. In order to solve these clinical problems, we realized the intraoperative molecular diagnosis of meningioma by combining real-time fluorescence PCR and AIGS, which is also the first known product applied to the intraoperative molecular diagnosis of meningioma.Implications for practiceWe applied AIGS to detect and track a patient with TERTp mutant meningioma, summarized the process of intraoperative molecular diagnosis, and expounded the significance of intraoperative molecular diagnosis under the new classification standard, hoping to optimize the clinical decision-making of meningioma through the diagnosis and treatment plan of this case

Formation of Active Sites for Oxygen Reduction Reactions by Transformation of Nitrogen Functionalities in Nitrogen-Doped Carbon Nanotubes

Heat treating nitrogen-doped multiwalled carbon nanotubes containing up to six different types of nitrogen functionalities transforms particular nitrogen functionalities into other types which are more catalytically active toward oxygen reduction reactions (ORR). In the first stage, the unstable pyrrolic functionalities transform into pyridinic functionalities followed by an immediate transition into quaternary center and valley nitrogen functionalities. By measuring the electrocatalytic oxidation reduction current for the different samples, we achieve information on the catalytic activity connected to each type of nitrogen functionality. Through this, we conclude that quaternary nitrogen valley sites, N-Q_valley, are the most active sites for ORR in N-CNTs. The number of electrons transferred in the ORR is determined from ring disk electrode and rotating ring disk electrode measurements. Our measurements indicate that the ORR processes proceed by a direct four-electron pathway for the N-Q_valley and the pyridinic sites while it proceeds by an indirect two-electron pathway <i>via</i> hydrogen peroxide at the N-Q_center sites. Our study gives both insights on the mechanism of ORR on different nitrogen functionalities in nitrogen-doped carbon nanostructures and it proposes how to treat samples to maximize the catalytic efficiency of such samples

Plasmonic metasurface assisted by thermally imprinted polymer nano‐well array for surface enhanced Raman scattering

Plasmonic nanometasurfaces/nanostructures possess strong electromagnetic field enhancement caused by resonant oscillations of free electrons, and has been extensively applied in biosensing, nanophotonic and photocatalysis. However, fabrication of uniform nanostructured metasurfaces by conventional methods is complicated and costly, which mitigates a wide-spread use of this technique in ubiquitous applications. Here, we present a facile and scalable method to fabricate an active nanotrench plasmonic gold substrate. The surface comprises sub-10 nm plasmonic nanogaps and their formation is assisted by a pre-fabrication of nano-imprinted polymer nano-well arrays. The plasmonic metasurface is optimized to maximize the density of the nano-trenches by tuning the substrate material, imprinting procedure and film deposition. We show that the surface Raman enhancement due to plasmonic resonances correlates well with trench density and reach a meritorious enhancement factor of EF &gt; 105 over large surfaces. We further show that the electric field strength at the nanotrench features are well explained by finite element method simulations using COMSOL Multiphysics. The plasmonic substrate is transparent in the visible spectrum and conductive. In combination with a scalable bottom-up fabrication the plasmonic metasurface opens up for a wider use of the sensitive and reliable SERS substrate in applications such as portable sensing devices and for future internet of things

Synthesis of Palladium/Helical Carbon Nanofiber Hybrid Nanostructures and Their Application for Hydrogen Peroxide and Glucose Detection

We report on a novel sensing platform for H₂O₂ and glucose based on immobilization of palladium-helical carbon nanofiber (Pd-HCNF) hybrid nanostructures and glucose oxidase (GOx) with Nafion on a glassy carbon electrode (GCE). HCNFs were synthesized by a chemical vapor deposition process on a C₆₀-supported Pd catalyst. Pd-HCNF nanocomposites were prepared by a one-step reduction free method in dimethylformamide (DMF). The prepared materials were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Raman spectroscopy. The Nafion/Pd-HCNF/GCE sensor exhibits excellent electrocatalytic sensitivity toward H₂O₂ (315 mA M^–1 cm^–2) as probed by cyclic voltammetry (CV) and chronoamperometry. We show that Pd-HCNF-modified electrodes significantly reduce the overpotential and enhance the electron transfer rate. A linear range from 5.0 μM to 2.1 mM with a detection limit of 3.0 μM (based on the S/N = 3) and good reproducibility were obtained. Furthermore, a sensing platform for glucose was prepared by immobilizing the Pd-HCNFs and glucose oxidase (GOx) with Nafion on a glassy carbon electrode. The resulting biosensor exhibits a good response to glucose with a wide linear range (0.06–6.0 mM) with a detection limit of 0.03 mM and a sensitivity of 13 mA M^–1 cm^–2. We show that small size and homogeneous distribution of the Pd nanoparticles in combination with good conductivity and large surface area of the HCNFs lead to a H₂O₂ and glucose sensing platform that performs in the top range of the herein reported sensor platforms

The role of pro-inflammatory S100A9 in Alzheimer's disease amyloid-neuroinflammatory cascade

Pro-inflammatory S100A9 protein is increasingly recognized as an important contributor to inflammation-related neurodegeneration. Here, we provide insights into S100A9 specific mechanisms of action in Alzheimer's disease (AD). Due to its inherent amyloidogenicity S100A9 contributes to amyloid plaque formation together with A beta. In traumatic brain injury (TBI) S100A9 itself rapidly forms amyloid plaques, which were reactive with oligomer-specific antibodies, but not with A beta and amyloid fibrillar antibodies. They may serve as precursor-plaques for AD, implicating TBI as an AD risk factor. S100A9 was observed in some hippocampal and cortical neurons in TBI, AD and non-demented aging. In vitro S100A9 forms neurotoxic linear and annular amyloids resembling A beta protofilaments. S100A9 amyloid cytotoxicity and native S100A9 pro-inflammatory signaling can be mitigated by its co-aggregation with A beta, which results in a variety of micron-scale amyloid complexes. NMR and molecular docking demonstrated transient interactions between native S100A9 and A beta. Thus, abundantly present in AD brain pro-inflammatory S100A9, possessing also intrinsic amyloidogenic properties and ability to modulate A beta aggregation, can serve as a link between the AD amyloid and neuroinflammatory cascades and as a prospective therapeutic target.Erratum available at http://dx.doi.org/10.1007/s00401-014-1316-9</p