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Substantial subpial cortical demyelination in progressive multiple sclerosis: have we underestimated the extent of cortical pathology?

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Neuroimmunology and Neuroinflammation 2020年第1期7卷 51-67页

作者： Lauren Griffiths richard reynolds Rhian Evans Ryan J.Bevan Mark I.Rees Djordje Gveric James W.Neal Owain W.Howell Institute of Life Sciences Swansea University Medical SchoolSwansea UniversitySwansea SA28PPUK Department of Brain Sciences Faculty of MedicineImperial College LondonLondon W53EHUK Faculty of Medicine and Health University of SydneySydneyNew South Wales NSW 2006Australia

Aim: Multiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease. Much of the complex symptomatology relates to pathology outside the classic white matter plaque, whereby lesions of the cortical grey matter, which are difficult to resolve by conventional clinical imaging, are in part predictive of outcome. We investigated the extent of grey matter pathology in whole coronal macrosections to reassess the contribution of cortical pathology to total demyelinating lesion area in progressive MS. Methods: Twenty-two cases of progressive MS were prepared as whole bi-hemispheric macrosections for histology, immunostaining and quantitative analysis of lesion number and relative area, leptomeningeal inflammation and microglial/macrophage activation. Results: Cortical grey matter demyelination was seen in all cases, which was more extensive than in white and deep grey matter (hippocampus, thalamus and basal ganglia) and accounted for 0.8%-60.2% of the entire measurable cortical ribbon. The pattern of cortical grey matter demyelination was predominantly subpial (mean 90.9%, range 60%-100%, of total cortical grey matter lesion area) and cases with the largest areas of subpial cortical lesions had more and larger deep grey matter lesions, greater numbers of activated microglia/macrophages, both in lesions as well as in normal cortical grey matter, together with elevated leptomeningeal inflammation and lymphoid-like ;structures. White matter lesion area was unchanged when compared with the progressive MS cases with little subpial cortical demyelination. Conclusion: Analysis of whole coronal macrosections reveals cortical demyelination is more extensive than reported by conventional histological methods. Cases of progressive MS with substantial subpial cortical demyelination that is independent of underlying white matter lesion area support the implications that these lesions may in-part arise through different pathogenetic mechanisms. Biomarkers and/or i

关键词： Leptomeninges B cell follicle microglia activation normal appearing grey matter

Dusts from dry lakebeds: Mineralogical and geochemical characteristics of potential health concern

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Chinese Journal Of Geochemistry 2006年第B08期25卷 223-223页

作者： Geoffrey S. Plumlee Suzette A. Morman richard L. reynolds Marith Reheis U.S. Geological Survey Denver Colorado USA

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脊髓多发性硬化斑块周围组织的重塑

神经损伤与功能重建 2014年第5期9卷 413-413页

作者： Alice Lieury Marie Chanal Géraldine Androdias richard reynolds Sylvie Cavagna Pascale Giraudon Christian Confavreux Serge Nataf 唐颖馨 Lyon Neuroscience Research Center Neuro-Oncology and Neuro-Inflammation TeamLyonFrance University Lyon 1 LyonFrance Service de Neurologie A and Euge` ne Devic Foundation Hopital Neurologique Pierre WertheimerHospicesCivils de Lyon (Lyon University Hospital)BronFrance Wolfson Neuroscience Laboratories Hammersmith Hospital CampusImperial College Faculty of MedicineLondonUnited Kingdom Banque de Cellules et de Tissus Hopital Edouard HerriotHospices Civils de Lyon (Lyon University Hospital)LyonFrance

关于多发性硬化(multiple sclerosis,MS)斑块的病理以及MS患者灰白质的弥散性改变,目前已有相当多的深入研究报道。但对于脱髓鞘斑块周围组织的改变,尤其对是脊髓MS斑块周围组织的病理研究,目前几乎没有报道。本研究即对进展性脊髓MS患... 详细信息

关于多发性硬化(multiple sclerosis,MS)斑块的病理以及MS患者灰白质的弥散性改变,目前已有相当多的深入研究报道。但对于脱髓鞘斑块周围组织的改变,尤其对是脊髓MS斑块周围组织的病理研究,目前几乎没有报道。本研究即对进展性脊髓MS患者的脊髓脱髓鞘病灶周围组织(periplaque demyelinated lesions,PDLs)进行分子免疫病理方面的研究。纳入初发或复发进展型脊髓MS患者21例,尸检得到其颈髓组织,对其PDLs的神经病理特征进行分析。结果显示,PDLs存在大面积的不完全性脱髓鞘现象,而且存在促炎症和抗炎症的叠加分子反应。巨噬细胞和小胶质细胞聚集在PDLs,但对脱髓鞘碎片的吞噬作用很弱。下调PDLs的少突胶质细胞基因,胶质细胞相关的分子标志物,如水通道蛋白(aquaporin)-4、缝隙连接蛋白(connexin)-43及谷氨酸转运子(glutamate transporter)EAAT1的mRNA及蛋白表达水平均明显下调。本研究还显示,在进展型脊髓MS患者的脊髓组织中,伴随脱髓鞘斑块的形成,PDLs内的组织重塑早已开始并一直伴随着斑块的形成。笔者推测脊髓病灶PDLs内,组织重塑的过程一定伴随着星形胶质细胞功能的改变、较轻的炎症反应,共同促进了脱髓鞘的发生和进展。

关键词：多发性硬化斑块周围脱髓鞘轴索损伤小胶质细胞星形胶质细胞

Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion

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World Journal of Gastroenterology 2017年第48期23卷 8443-8451页

作者： Yuri L Boteon richard Laing Hynek Mergental Gary M reynolds Darius F Mirza Simon C Afford Ricky H Bhogal The Liver Unit University Hospitals of BirminghamMindelsohn Way The Centre for Liver Research Institute for Biomedical ResearchUniversity of Birmingham

Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.

关键词： Autophagy Liver transplant Ischaemiareperfusion injury Normothermic machine liver perfusion

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男性避孕:回顾与展望

英国医学杂志中文版 2022年第7期25卷 393-398页

作者： John Joseph reynolds-Wright richard A Anderson 王涛(译) 李铮(校) MRC Centre for Reproductive Health The Queen's Medical Research InstituteUniversity of EdinburghEdinburghUK 华中科技大学同济医学院附属同济医院泌尿外科上海交通大学医学院附属第一人民医院泌尿中心男科

新型可逆性男用避孕药的研发进展缓慢。虽然研究已充分表明激素类药物具备有效和可逆的避孕作用,但仍然没有此类药物应用于临床。目前,正在研发一种睾酮和孕激素的自用凝胶Nestorone@,而以往研究更多采用的是注射给药方法。具有雄激素... 详细信息

新型可逆性男用避孕药的研发进展缓慢。虽然研究已充分表明激素类药物具备有效和可逆的避孕作用,但仍然没有此类药物应用于临床。目前,正在研发一种睾酮和孕激素的自用凝胶Nestorone@,而以往研究更多采用的是注射给药方法。具有雄激素和孕激素活性的新型长效类固醇制剂,也正在进行早期临床试验。非激素疗法作用于精子发生的潜在位点,或干扰附睾或输精管中的精子成熟,具有某些潜在的优势,但仍处于临床前试验阶段。调查表明男性及其伴侣更愿意尝试新的男性避孕方法,只是没有相关产品上市。

关键词：避孕作用药物应用激素类药物注射给药孕激素精子发生男性避孕雄激素

Textiles from non-wood feedstocks: Challenges and opportunities of current and emerging fiber spinning technologies

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Journal of Bioresources and Bioproducts 2024年第4期9卷 410-432页

作者： Ryen M.Frazier Mariana Lendewig Ramon E.Vera Keren A.Vivas Naycari Forfora Ivana Azuaje Autumn reynolds richard Venditti Joel J.Pawlak Ericka Ford Ronalds Gonzalez Department of Forest Biomaterials North Carolina State UniversityRaleighNC 27695USA Department of Textile Engineering Chemistry and ScienceThe Nonwovens InstituteNorth Carolina State UniversityRaleighNC 27695USA

As the global population continues growing, the demand for textiles also increases, putting pres- sure on cotton manufacturers to produce more natural fiber from this already undersupplied resource. Synthetic fibers such as polyester (PET) can be manufactured quickly and cheaply, but these petroleum-based products are detrimental to the environment. With increased efforts to encourage transparency and create a more circular textile economy, other natural alternatives must be considered. This article discusses the existing condition and future possibilities for man- made cellulosic fibers (MMCFs), with an emphasis on using non-woody alternative feedstocks as a starting material. This work focuses on conversion technology suitable for producing textile- grade fibers from non-wood-based dissolving pulp, which may be different in nature from its woody counterpart and therefore behave differently in spinning processes. Derivatization and dissolution methods are detailed, along with spinning techniques and parameters for these pro- cesses. Existing research related to the spinning of non-woody-based dissolving pulp is covered, along with suggestions for the most promising feedstock and technology combinations. In addi- tion, an emerging method of conversion, in which textile fibers are spun from a hydrogel made of an undissolved nano/micro-fibrillated fiber suspension, is briefly discussed due to its unique po- tential. Methods and concepts compiled in this review relate to utilizing alternative feedstocks for future fibers while providing a better understanding of conventional and emerging fiber spinning processes for these fibers.

关键词： Non-wood Residue Regenerated cellulose Fibrillated cellulose Biobased fiber Textile Man-made cellulosic fiber

Lattice approaches to packed column simulations

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Particuology 2008年第6期6卷 404-411页

作者： richard Caulkin Mike Fairweather richard A. Williams Institute of Particle Science and Engineering School of ProcessEnvironmental and Materials EngineeringUniversity of Leeds

This work presents a review of the findings into the ability of a digitally based particle packing algorithm, called DigiPac, to predict bed structure in a variety of packed columns, for a range of generic pellet shapes frequently used in the chemical and process engineering industries. Resulting macroscopic properties are compared with experimental data derived from both invasive and non-destructive measurement techniques. Additionally, fluid velocity distributions, through samples of the resulting bed structures, are analysed using lattice Boltzmann method （LBM） simulations and are compared against experimental data from the literature.

关键词： Packing algorithm Bed structure Packed columns Macroscopic properties Lattice Boltzmann simulations

Expected adult lifespan in tropical trees: Long-term matrix demography in a large plot

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Forest Ecosystems 2022年第4期9卷 558-566页

作者： richard Condit Morton Arboretum 4100 Illinois Rte.53LisleIL60532USA Institute for Marine Sciences University of CaliforniaSanta CruzUSA

Background: Documenting the entire lifetime of long-lived organisms requires splicing together short-term observations. Matrix demography provides a tool to calculate lifetime statistics, but large samples from juvenile to adult are needed, and few such studies have been done in tropical trees because high species diversity limits sample sizes. The 50-ha plot at Barro Colorado in Panama was designed to provide large samples, and with 30years of censuses, accurate population matrices can be ***: In 31 abundant species, I divided all individuals≥1 cm dbh into 4 or 5 size class in each of seven censuses. Movements of stems between size classes over two censuses are termed transitions, and I constructed complete transition matrices for each species. From the matrices, I derived analytic solutions for lifetime demographic statistics. Expected adult lifespan from the sapling stage was the key ***: Expected adult lifespan from the sapling stage varied 100-fold over the 31 species, from 0.5 to 50 years,and maturation time varied from 19 to nearly 200 years. Species with the highest growth rates also had high death rates, and theoretical calculations of reproductive lifespan show that the fast-growing pioneer species have short expected adult lifespans relative to the average slow-growing, shade-tolerant species. Within the slowgrowth category, however, there was high variation in expected adult lifespan, and several shade-tolerant species under-performed the pioneers in terms of adult ***: Analytical solutions from population matrices allow theoretical analyses that integrate short-term growth records into lifespans of tropical trees. The analyses suggest that pioneer species must reproduce more successfully than shade-tolerant species to persist in the Barro Colorado forest. My next goal is to incorporate seed production and germination into lifetime matrix demography to test this hypothesis.

关键词： Tree lifespan Tropical tree Matrix demography

Bound and Resonating Multiquark Configurations

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Chinese Physics Letters 2024年第8期41卷 8-12页

作者： Jean-Marc richard Institut de Physique des 2 Infinis de Lyon Université Claude Bernard(Lyon 1) CNRS-IN2P34 rue Enrico Fermi69622 VilleurbanneFrance

We review the predictions of quark models for multiquark configurations that are bound or resonant states,and compare different methods for estimating the properties of resonances.

关键词： quark Configuration resonant