Label-Free Fluorescence Spectroscopy for Detecting Key Biomolecules in Brain Tissue from a Mouse Model of Alzheimer’s Disease

In this study, label-free fluorescence spectroscopy was used for the first time to determine spectral profiles of tryptophan, reduced nicotinamide adenine dinucleotide (NADH), and flavin denine dinucleotide (FAD) in fresh brain samples of a mouse model of Alzheimer’s disease (AD). Our results showed that the emission spectral profile levels of tryptophan and NADH were higher in AD samples than normal samples. The intensity ratio of tryptophan to NADH and the change rate of fluorescence intensity with respect to wavelength also increased in AD brain. These results yield an optical method for detecting early stage of AD by comparing spectral profiles of biomolecules

Lower-Molecular-Weight Chitosan-Treated Polyethyleneimine: a Practical Strategy For Gene Delivery to Mesenchymal Stem Cells

Background/Aims: Genetic modification of mesenchymal stem cells (MSCs) is an essential requirement for their use as a delivery vehicle. To achieve higher transfection efficiency and better reproducibility than previously synthesized chitosan (100 kDa)-polyethylenimine (PEI; 1200 Da), we synthesized a low molecular weight PEI (1200 Da)-grafted chitosan (50 kDa) (CP). Methods: Safety of CP/DNA or PEI (25 kDa)/DNA was evaluated by an MTT assay using A549 cells or MSCs and a zebrafish embryo model. Effects of CP/DNA on the characteristics of MSCs were evaluated using flow cytometry. Additionally, a pGL3 plasmid was used to investigate the transfection efficiency of PEI (25 kDa), chitosan (100 kDa)-PEI (1200 Da), and CP with different N/P mass ratios on A549 cells and MSCs. Furthermore, CP/pGL3 was used to investigate the effect of serum on transfection, and intracellular transport was assessed by observing the intracellular location of DNA using laser scanning confocal microscopy. In addition, the effect of endocytosis on transfection efficiency was evaluated using A549 cells pre-treated with different inhibitors. Investigations related to analysis of transfection efficiency were all performed using the BCA protein assay to standardize the data. Furthermore, TGF-β1-and CXCR4-expressing plasmids were applied to evaluate the gene transfer efficiency of CP, including its effects on the osteogenic differentiation and migratory ability of MSCs. Results: The safety evaluation demonstrated that CP/DNA had significantly lower toxicity than PEI (25 kDa)/DNA. Additionally, DNA entered MSCs transfected by CP without changing their properties, while the examination of intracellular transport demonstrated that CP/pGL3 was internalized rapidly into MSCs. Furthermore, studies of the internalization mechanism showed that CP/pGL3 complexes entered the cells through caveolae-mediated endocytosis, thereby suggesting that the CP coating helped DNA enter A549 cells without the requirement for receptors. Compared to PEI (25 kDa), the interference of serum on transfection was reduced significantly with the use of CP in both A549 cells and MSCs. To evaluate the effects of gene delivery using the constructed CP complex and the possibility of obtaining gene-engineered MSCs, TGF-β1- and CXCR4-expressing plasmids were successfully delivered into MSCs, confirming their ability to induce osteogenesis and change the migratory ability of MSCs, respectively. Conclusion: These results demonstrated that CP could be used to deliver genes into MSCs and could potentially be used in gene therapy based on MSCs

A Novel Loss Function Incorporating Imaging Acquisition Physics for PET Attenuation Map Generation using Deep Learning

In PET/CT imaging, CT is used for PET attenuation correction (AC). Mismatch between CT and PET due to patient body motion results in AC artifacts. In addition, artifact caused by metal, beam-hardening and count-starving in CT itself also introduces inaccurate AC for PET. Maximum likelihood reconstruction of activity and attenuation (MLAA) was proposed to solve those issues by simultaneously reconstructing tracer activity ($\lambda$-MLAA) and attenuation map ($\mu$-MLAA) based on the PET raw data only. However, $\mu$-MLAA suffers from high noise and $\lambda$-MLAA suffers from large bias as compared to the reconstruction using the CT-based attenuation map ($\mu$-CT). Recently, a convolutional neural network (CNN) was applied to predict the CT attenuation map ($\mu$-CNN) from $\lambda$-MLAA and $\mu$-MLAA, in which an image-domain loss (IM-loss) function between the $\mu$-CNN and the ground truth $\mu$-CT was used. However, IM-loss does not directly measure the AC errors according to the PET attenuation physics, where the line-integral projection of the attenuation map ($\mu$) along the path of the two annihilation events, instead of the $\mu$ itself, is used for AC. Therefore, a network trained with the IM-loss may yield suboptimal performance in the $\mu$ generation. Here, we propose a novel line-integral projection loss (LIP-loss) function that incorporates the PET attenuation physics for $\mu$ generation. Eighty training and twenty testing datasets of whole-body 18F-FDG PET and paired ground truth $\mu$-CT were used. Quantitative evaluations showed that the model trained with the additional LIP-loss was able to significantly outperform the model trained solely based on the IM-loss function.Comment: Accepted at MICCAI 201

A bibliometric and visualization study of global research trends in sacral Tarlov cyst from 2000 to 2022

BackgroundSymptomatic sacral Tarlov cyst (STC) exerts a significant negative impact on the patient's quality of life, highlighting the significance of the increasing number of studies on STC. However, bibliometric analyses in this research field are scarce. Thus, this study aims to provide a comprehensive knowledge structure and identify the research trends of STC through bibliometrics.MethodsArticles related to STC from 2000 to 2022 were sourced from the Web of Science Core Collection database. VOSviewer 1.6.16, CiteSpace 6.1.6, GraphPad Prism 8.2.1 and R-package “bibliometrix” were used to analyse the data and generate knowledge maps.ResultsA total of 930 studies on STC from 2000 to 2022 were included. The findings revealed a consistent yet upward trend in the number of annual publications in this field. The United States, China and Turkey were the most prolific and influential countries contributing to this field, with the University of Illinois, the University of Maryland and the National Institute of Standards & Technology being the most notable research institutions. Key journals include World Neurosurgery [Impact Factor (IF) = 2.210], Journal of Vascular Surgery (IF = 4.860) and Journal of Neurosurgery-Spine (IF = 3.467). Additionally, Tarlov Mj, Tarlov E and Zachariah Mr exhibit the highest number of publications, making them the leading authors in this field. A twenty-year retrospection of research trends using keyword analysis reveals four principal directions, namely “definition”, “pathogenesis”, “diagnosis” and “treatment”. Currently, therapeutic surgical intervention is the key treatment for this disease, with future treatments primarily hinging on minimally invasive methodologies rooted in microendoscopic and endoscopic techniques.ConclusionThis pioneering, comprehensive scientific bibliometric study provides a holistic summary of STC research trends and hot spots spanning the past 22 years. The results identify existing research frontiers and chart maps for future studies, serving as a valuable reference for scholars vested in this field