Development of a Miniature Mass Spectrometry System for Point-of-Care Analysis of Lipid Isomers Based on Ozone-Induced Dissociation

Disorder of lipid homeostasis is closely associated with a variety of diseases. Although mass spectrometry (MS) approaches have been well developed for the characterization of lipids, it still lacks an integrated and compact MS system that is capable of rapid and detailed lipid structural characterization and can be conveniently transferred into different laboratories. In this work, we describe a novel miniature MS system with the capability of both ozone-induced dissociation (OzID) and collision-induced dissociation (CID) for the assignment of sites of unsaturation and sn-positions in glycerolipids. A miniature ozone generator was developed, which can be operated at a relatively high pressure. By maintaining high-concentration ozone inside the linear ion trap, OzID efficiency was significantly improved for the identification of CC locations in unsaturated lipids, with reaction times as short as 10 ms. Finally, the miniature OzID MS system was applied to the analysis of CC locations and sn-positions of lipids from biological samples. Direct sampling and fast detection of changes in phospholipid isomers were demonstrated for the rapid discrimination of breast cancer tissue samples, showing the potential of the miniature OzID MS system for point-of-care analysis of lipid isomer biomarkers in complex samples

Light-Up Nonthiolated Aptasensor for Low-Mass, Soluble Amyloid‑β₄₀ Oligomers at High Salt Concentrations

Herein, a light-up nonthiolated aptasensor was developed for low-mass, soluble amyloid-β₄₀ oligomers (LS-Aβ_40‑O). Au nanoparticles (AuNP) were employed as colorimetric probes, and the nonthiolated aptamers (Apt) were adsorbed on AuNP surfaces, acting as binding elements for LS-Aβ_40‑O. The aggregation of AuNPs was induced when Apt-modified AuNPs (Apt@AuNPs) were under high-salt conditions. However, upon the addition of LS-Aβ_40‑O into the Apt@AuNP solution, the salt tolerance of the AuNPs was greatly enhanced. Further studies confirmed that the formed LS-Aβ_40‑O–Apt complex attached onto the AuNP surfaces via interactions between LS-Aβ_40‑O and Au, which led to electrostatic and steric stabilization of the AuNPs under high-salt conditions. On the basis of this outcome, a sensitive light-up nonthiolated aptasensor for LS-Aβ_40‑O was achieved with a detection limit of 10.0 nM and a linear range from 35.0 to 700 nM in a 175 mM NaCl solution. Cerebrospinal-fluid (CSF) samples from healthy persons and Alzheimer’s disease (AD) patients were successfully distinguished by using this proposed method. The concentrations of LS-Aβ_40‑O in the CSF of AD patients were of nanomolar grade, but there was no detectable LS-Aβ_40‑O in those of the healthy persons. This work provides a new insight into the interaction between Apt@AuNPs and Aβ_40‑O and also develops a simple, rapid, highly selective and sensitive, and applicable method for LS-Aβ_40‑O detection in real CSF samples, which is significant for the diagnosis of AD

Distribution of the GGGGCC repeats size in SCA3/MJD patients and controls.

<p>There was no significant difference in the distribution of the GGGGCC repeats length between SCA3/MJD patients and controls.</p

Demographic information and average number of repeats between SCA3/MJD patients and controls.

<p>^a x ² test.</p><p>^b t-tests.</p><p>^c Mann-Whitney U test.</p><p>Demographic information and average number of repeats between SCA3/MJD patients and controls.</p

Frequencies of C9orf72 genotypes.

<p>A presents the frequencies in SCA3/MJD patients. B presents the frequencies in controls.</p

Analysis of the GGGGCC Repeat Expansions of the <i>C9orf72</i> Gene in SCA3/MJD Patients from China

<div><p>Neurodegenerative disorders are a heterogeneous group of chronic progressive diseases and have pathological mechanisms in common. A certain causative gene identified for a particular disease may be found to play roles in more than one neurodegenerative disorder. We analyzed the GGGGCC repeat expansions of <i>C9orf72</i> gene in patients with SCA3/MJD from mainland China to determine whether the <i>C9orf72</i> gene plays a role in the pathogenesis of SCA3/MJD. In our study, there were no pathogenic repeats (>30 repeats) detected in either the patients or controls. SCA3/MJD patients with intermediate/intermediate or short/intermediate genotype (short: <7 repeats; intermediate: 7-30 repeats) of the GGGGCC repeats had an earlier onset compared with those with short/short genotype. The presence of the intermediate allele of the GGGGCC repeats in the patients decreased the age at onset by nearly 3 years. Our study firstly demonstrate that the development of SCA3/MJD may involve some physiological functions of the <i>C9orf72</i> gene and provide new evidence to the hypothesis that a specific mutation identified in one of the neurodegenerative disorders may be a modulator in this class of diseases.</p></div

Additional file 1: of Shanghai cognitive intervention of mild cognitive impairment for delaying progress with longitudinal evaluation-a prospective, randomized controlled study (SIMPLE): rationale, design, and methodology

Description of neuropsychological battery. Here is the description of neuropsychological assessments used in in the SIMPLE study, including their versions, scores and clinical significance. (DOCX 35 kb