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Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

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Nano Research 2016年第8期9卷 2384-2397页

作者： Alan P. Weightman Stuart I. Jenkins Divya M. Chari Cellular and Neural Engineering Group Institute for Science and Technology in Medicine Huxley Building Keele University Keele ST55BG UK

Development of nanoparticle （NP） based therapies to promote regeneration in sites of central nervous system （CNS; i.e, brain and spinal cord） pathology relies critically on the availability of experimental models that offer biologically valid predictions of NP fate in vivo. However, there is a major lack of biological models that mimic the pathological complexity of target neural sites in vivo, particularly the responses of resident neural immune cells to NPs. Here, we have utilised a previously developed in vitro model of traumatic spinal cord injury （based on 3-D organotypic slice arrays） with dynamic time lapse imaging to reveal in real-time the acute cellular fate of NPs within injury foci. We demonstrate the utility of our model in revealing the well documented phenomenon of avid NP sequestration by the intrinsic immune cells of the CNS （the microglia）. Such immune sequestration is a known translational barrier to the use of NP-based therapeutics for neurological injury. Accordingly, we suggest that the utility of our model in mimicking microglial sequestration behaviours offers a valuable investigative tool to evaluate strategies to overcome this cellular response within a simple and biologically relevant experimental system, whilst reducing the use of live animal neurological injury models for such studies.

关键词： organotypic slice culture microglia immune barrier corticosteroid dexamethasone time lapse microscopy

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Contact pattern,current immune barrier,and pathogen virulence determines the optimal strategy of further vaccination

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Infectious Disease Modelling 2023年第1期8卷 192-202页

作者： Xiaohao Guo Ziyan Liu Shiting Yang Zeyu Zhao Yichao Guo Guzainuer Abudurusuli Shanlu Zhao Ge Zeng Shixiong Hu Kaiwei Luo Tianmu Chen State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthXiamen UniversityXiamen City361102Fujian ProvincePeople's Republic of China Hunan Provincial Center for Disease Control and Prevention 405 Furong Middle Road Section OneKaifu DistrictChangsha City410001Hunan ProvincePeople's Republic of China

Background:The current outbreak of novel coronavirus disease 2019 has caused a seriousdisease burden *** are an important factor to sustain the *** with a relatively high-vaccination worldwide,the decay of vaccine efficacy andthe arising of new variants lead us to the challenge of maintaining a sufficient immunebarrier to protect the ***:A case-contact tracking data in Hunan,China,is used to estimate the contactpattern of cases for scenarios including school,workspace,etc,rather than ordinary susceptible *** on the estimated vaccine coverage and efficacy,a multi-groupvaccinated-exposed-presymptomatic-symptomatic-asymptomatic-removed model(VEFIAR)with 8 age groups,with each partitioned into 4 vaccination status groups *** optimal dose-wise vaccinating strategy is optimized based on the currentlyestimated immunity barrier of coverage and efficacy,using the greedy algorithm thatminimizes the cumulative cases,population size of hospitalization and fatality respectivelyin a certain future *** of Delta and Omicron variants are used respectivelyin the ***:The estimated contact matrices of cases showed a concentration on middle ages,and has compatible magnitudes compared to estimations from contact surveys in *** VEFIAR model is numerically *** optimal controled vaccination strategy requires immediate vaccination on the un-vaccinated high-contact population of age30e39 to reduce the cumulative cases,and is stable with different basic reproductionnumbers(R_(0)).As for minimizing hospitalization and fatality,the optimized strategy requires vaccination on the un-vaccinated of both aged 30e39 of high contact frequencyand the vulnerable ***:The objective of reducing transmission requires vaccination in age groups ofthe highest contact frequency,with more priority for un-vaccinated than un-fully or *** objective of reducing total ho

关键词： Vaccine Allocation strategy SARS-CoV-2 Optimal control immune barrier Contact pattern Greedy algorithm

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