Functional equivalence of stem cell and stem cell-derived extracellular vesicle transplantation to repair the irradiated brain.

Cranial radiotherapy, although beneficial for the treatment of brain tumors, inevitably leads to normal tissue damage that can induce unintended neurocognitive complications that are progressive and debilitating. Ionizing radiation exposure has also been shown to compromise the structural integrity of mature neurons throughout the brain, an effect believed to be at least in part responsible for the deterioration of cognitive health. Past work has shown that cranially transplanted human neural stem cells (hNSCs) or their extracellular vesicles (EVs) afforded long-term beneficial effects on many of these cognitive decrements. To provide additional insight into the potential neuroprotective mechanisms of cell-based regenerative strategies, we have analyzed hippocampal neurons for changes in structural integrity and synaptic remodeling after unilateral and bilateral transplantation of hNSCs or EVs derived from those same cells. Interestingly, hNSCs and EVs similarly afforded protection to host neurons, ameliorating the impact of irradiation on dendritic complexity and spine density for neurons present in both the ipsilateral and contralateral hippocampi 1 month following irradiation and transplantation. These morphometric improvements were accompanied by increased levels of glial cell-derived growth factor and significant attenuation of radiation-induced increases in postsynaptic density protein 95 and activated microglia were found ipsi- and contra-lateral to the transplantation sites of the irradiated hippocampus treated with hNSCs or hNSC-derived EVs. These findings document potent far-reaching neuroprotective effects mediated by grafted stem cells or EVs adjacent and distal to the site of transplantation and support their potential as therapeutic agents to counteract the adverse effects of cranial irradiation

Mapping Posttranscriptional Regulation of the Human Glycome Uncovers microRNA Defining the Glycocode

Cell surface glycans form a critical interface with the biological milieu, informing diverse processes from the inflammatory cascade to cellular migration. Assembly of discrete carbohydrate structures requires the coordinated activity of a repertoire of proteins, including glycosyltransferases and glycosidases. Little is known about the regulatory networks controlling this complex biosynthetic process. Recent work points to a role for microRNA (miRNA) in the regulation of specific glycan biosynthetic enzymes. Herein we take a unique systems-based approach to identify connections between miRNA and the glycome. By using our glycomic analysis platform, lectin microarrays, we identify glycosylation signatures in the NCI-60 cell panel that point to the glycome as a direct output of genomic information flow. Integrating our glycomic dataset with miRNA data, we map miRNA regulators onto genes in glycan biosynthetic pathways (glycogenes) that generate the observed glycan structures. We validate three of these predicted miRNA/glycogene regulatory networks: high mannose, fucose, and terminal β-GalNAc, identifying miRNA regulation that would not have been observed by traditional bioinformatic methods. Overall, our work reveals critical nodes in the global glycosylation network accessible to miRNA regulation, providing a bridge between miRNA-mediated control of cell phenotype and the glycome

Simulation study of BESIII with stitched CMOS pixel detector using ACTS

Reconstruction of tracks of charged particles with high precision is very crucial for HEP experiments to achieve their physics goals. As the tracking detector of BESIII experiment, the BESIII drift chamber has suffered from aging effects resulting in degraded tracking performance after operation for about 15 years. To preserve and enhance the tracking performance of BESIII, one of the proposals is to add one layer of thin CMOS pixel sensor in cylindrical shape based on the state-of-the-art stitching technology, between the beam pipe and the drift chamber. The improvement of tracking performance of BESIII with such an additional pixel detector compared to that with only the existing drift chamber is studied using the modern common tracking software ACTS, which provides a set of detector-agnostic and highly performant tracking algorithms that have demonstrated promising performance for a few high energy physics and nuclear physics experiments

A novel community driven software for functional enrichment analysis of extracellular vesicles data.

Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture "what the community needs in a tool". Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes. Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features. FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database. By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment

Cancers are defined by genetic defects, which underlines the prospect of using gene therapy in patient care. During the past decade, CRISPR technology has rapidly evolved into a powerful gene editing tool with high fidelity and precision. However, one of the impediments slowing down the clinical translation of CRISPR-based gene therapy concerns the lack of ideal delivery vectors. Extracellular vesicles (EVs) are nano-sized membrane sacs naturally released from nearly all types of cells. Although EVs are secreted for bio-information conveyance among cells or tissues, they have been recognized as superior vectors for drug or gene delivery. Recently, emerging evidence has spotlighted EVs in CRISPR delivery towards cancer treatment. In this review, we briefly introduce the biology and function of the CRISPR system and follow this with a summary of current delivery methods for CRISPR applications. We emphasize the recent progress in EV-mediated CRISPR editing for various cancer types and target genes. The reported strategies for constructing EV-CRISPR vectors, as well as their limitations, are discussed in detail. The review aims to throw light on the clinical potential of engineered EVs and encourage the expansion of our available toolkit to defeat cancer

A Review of the Preparation, Analysis and Biological Functions of Chitooligosaccharide

Chitooligosaccharide (COS), which is acknowledged for possessing multiple functions, is a kind of low-molecular-weight polymer prepared by degrading chitosan via enzymatic, chemical methods, etc. COS has comprehensive applications in various fields including food, agriculture, pharmacy, clinical therapy, and environmental industries. Besides having excellent properties such as biodegradability, biocompatibility, adsorptive abilities and non-toxicity like chitin and chitosan, COS has better solubility. In addition, COS has strong biological functions including anti-inflammatory, antitumor, immunomodulatory, neuroprotective effects, etc. The present paper has summarized the preparation methods, analytical techniques and biological functions to provide an overall understanding of the application of COS

Study on Valve Strategy of Variable Cylinder Deactivation Based on Electromagnetic Intake Valve Train

The camless electromagnetic valve train (EMVT), as a fully flexible variable valve train, has enormous potential for improving engine performances. In this paper, a new valve strategy based on the electromagnetic intake valve train (EMIV) is proposed to achieve variable cylinder deactivation (VCD) on a four-cylinder gasoline engine. The 1D engine model was constructed in GT-Power according to test data. In order to analyze the VCD operation with the proposed valve strategy, the 1D model was validated using a 3D code. The effects of the proposed valve strategy were investigated from the perspective of energy loss of the transition period, the mass fraction of oxygen in the exhaust pipe, and the minimum in-cylinder pressure of the active cycle. On the premise of avoiding high exhaust oxygen and oil suction, the intake valve timing can be determined with the variation features of energy losses. It was found that at 1200 and 1600 rpm, fuel economy was improved by 12.5⁻16.6% and 9.7⁻14.6%, respectively, under VCD in conjunction with the early intake valve closing (EIVC) strategy when the brake mean effective pressure (BMEP) ranged from 0.3 MPa to 0.2 MPa