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An amyloid-beta peptide (Aβ) is generally believed to be a pathological marker of Alzheimer's disease (AD), but it is still of great significance to explore the upstream and downstream relationship of Aβ in AD. It is previously reported that c-Abl, a nonreceptor tyrosine kinase, can be activated by Aβ, but the interaction between Aβ and c-Abl is still unknown. Herein, an extended-gate field-effect transistor (EG-FET)-based sensor has been developed to monitor the level of c-Abl with high sensitivity and selectivity. Our peptide-functionalized EG-FET sensor as the signal transducer can follow c-Abl activity with electron transfer by its specific phosphorylation. The sensor presents a good linear correlation over c-Abl concentrations of 1 pg/mL to 3.05 μg/mL. The sensor was successfully applied to quantify c-Abl activity in the brain tissue of AD transgenic mice, and the interaction between c-Abl and Aβ in AD mice was explored by administering the c-Abl inhibitor (imatinib) and the agonist (DPH). Our work is expected to provide an important reference for early diagnosis and treatment of AD.

As more researchers have acknowledged that the aggregation of amyloid β (Aβ) peptides might only be a pathological phenomenon that appears during the course of Alzheimer's disease (AD), it is therefore of great significance to have a preclinical or an early clinical diagnosis. Cu

Herein, we provide a proof of concept for a novel strategy that targets the assessment of the aggregation of amyloid-β (Aβ) by simultaneously determining its oligomers (Aβo) and fibrils (Aβf) in one analytical system. By fabricating and combining two immunosensors for Aβo and Aβf, respectively, we constructed a two-channel electrochemical system. The ratio of Aβf to Aβo was calculated and taken as a possible criterion for evaluating the extent of aggregation. Thereby, the presence of and transformation between oligomers and fibrils were accurately probed by incubating the Aβ monomer for different times and then calculating the ratios of Aβf to Aβo. The applicability of this method was further validated by tracking the dynamic progress of Aβ aggregation in the cerebrospinal fluid and tissues of Alzheimer's disease (AD) rats, which revealed that the ratio of Aβf to Aβo in rat brain gradually increased with the progression of AD, which was indicative of the severity of peptide aggregation during this process. Overall, this study represents the first example of a quantitative strategy for precisely evaluating the aggregation process that is related to pathological events in AD brain.

Herein, we developed a sensitive graphitic carbon nitride quantum dot (gCNQD)-based fluorescent strategy for β-amyloid peptide monomer (Aβ) determination down to the ng mL-1 level for the first time. To realize this goal, the nanostructured gCNQDs were firstly coordinated with four transition metal ions (Cu2+, Cu+, Fe3+, Zn2+). Our findings showed that the fluorescence (FL) intensity of gCNQDs was quenched in the presence of these metal ions possibly due to the effective chelation with the nitrogen element in gCNQDs and subsequent photoinduced electron transfer (PET) of gCNQDs. The degree of fluorescence quenching was found to be the most intense with the addition of Cu2+ and therefore, we selected Cu2+ as the quencher for the following Aβ determination. Through binding to Cu2+, the introduction of Aβ unexpectedly induced a further decline of FL intensity. Importantly, on account of different peptide sequences coexisting in the same cerebral system, including Aβ1-11, Aβ1-16, Aβ1-38, Aβ1-40 and Aβ1-42, their affinities to Cu2+ could be reflected by the distinguished declining extent of FL intensity. The possible mechanism of Aβ sensing by the probe was clarified by TEM characterization. The developed fluorescent biosensor was demonstrated to give a wide linear range from 1 to 700 ng mL-1 and a low detection limit of 0.18 ng mL-1 for Aβ1-42. In the end, the proposed fluorescence approach was successfully applied to monitoring of Aβ1-42 variations in the cortex and hippocampus of AD rats.

Blood oxygen saturation (SO2) reflects the oxygenation level in blood transport and tissue. Previous studies have shown the capability of non-invasive quantitative measurements of SO2 by multi-wavelength photoacoustic (PA) spectroscopy for diagnosis of brain, tumor hemodynamics, and other pathophysiological phenomena. Here, we report a newly proposed method by combining PA and scattered light signals wherein imposing a hypothesis that scattering intensity is linear to the concentrations of oxygenated hemoglobin and deoxygenated hemoglobin weighed by blood scattering coefficients. A rigorous theoretical relationship between PA and scattering signals is thus established, making it possible that SO2 can be measured with only one excitation wavelength after calibration. To verify the theory basis, both dual-ink phantoms and fresh porcine blood sample have been employed in the experiments. The phantom experiment is able to quantify the concentration of mixed red–green ink that is in precise agreement with pre-set values. The in vitro experiment with fresh porcine blood was conducted, and the results of the proposed single-wavelength method achieved reasonable accuracy with 5%–8% errors. These demonstrated that the proposed single-wavelength SO2 detection method is able to provide non-invasive, accurate measurement of blood oxygenation combining optical absorption and scattering.

Background & Aims: There is increasing need for accurate assessment of liver fibrosis/cirrhosis. We aimed to develop qFibrosis, a fully-automated assessment method combining quantification of histopathological architectural features, to address unmet needs in core biopsy evaluation of fibrosis in chronic hepatitis B (CHB) patients.Methods: qFibrosis was established as a combined index based on 87 parameters of architectural features. Images acquired from 25 Thioacetamide-treated rat samples and 162 CHB core biopsies were used to train and test qFibrosis and to demonstrate its reproducibility. qFibrosis scoring was analyzed employing Metavir and Ishak fibrosis staging as standard references, and collagen proportionate area (CPA) measurement for comparison. Results: qFibrosis faithfully and reliably recapitulates Metavir fibrosis scores, as it can identify differences between all stages in both animal samples (p