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Neural regeneration research 2025年第4期20卷 1081-1082页

作者： john Mitrofanis Jonathan Stone Michael r.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

慢性阻塞性肺疾病患者支气管肺泡灌洗液细菌宏基因组DNA的制备

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微生物学报 2014年第8期54卷 943-949页

作者：王娟沈宁杜毅鹏 john r erb.downward Gary B Huffnagle Margaret r Gyetko 贺蓓北京大学第三医院呼吸科北京100191 密西根大学医学院内科呼吸与危重症医学科美国北京大学医学部-密歇根大学医学院转化医学与临床研究联合研究所北京100191

【目的】优化稳定期慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)患者支气管肺泡灌洗液(bronchoalveolar lavage fluids,BALF)细菌宏基因组DNA的提取方法,以便于高效提取微量的细菌DNA进行后续的PCr反应和测序。【... 详细信息

【目的】优化稳定期慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)患者支气管肺泡灌洗液(bronchoalveolar lavage fluids,BALF)细菌宏基因组DNA的提取方法,以便于高效提取微量的细菌DNA进行后续的PCr反应和测序。【方法】取稳定期COPD患者的BALF 5mL,离心收集细胞。为了有效提取样品中革兰氏阳性菌的基因组,对QIAGEN的DNA提取试剂盒的操作步骤进行优化:加入裂解缓冲液ATL后首先运用研磨珠和多功能生物样品匀质器破碎菌壁,再加入蛋白酶K孵育,然后加入裂解缓冲液AL振荡混匀。无水乙醇沉淀DNA后,将全部溶液过柱,用洗液AW1和AW2各洗柱一次,最后加50μL洗脱液洗脱DNA。提取的DNA定量后,运用PCr方法检测样本中的细菌16S rDNA量,并按照测序要求构建DNA文库进一步验证。【结果】试剂盒优化法提取的BALF的DNA总量为467.5(135.0-1697.5)ng,明显高于按照传统酚-氯仿法提取的DNA总量95.0(0-612.5)ng,并且所提取的DNA可以很好的扩增细菌的16S rDNA以及构建DNA文库,改良后的扩增产物明显增多(P=0.002)。【结论】使用DNA提取试剂盒结合研磨珠和多功能生物样品匀质器破菌壁的方法能够更高效的提取BALF中微量的宏基因组DNA,为进一步的测序和菌群分析打下基础。

关键词：慢性阻塞性肺疾病支气管肺泡灌洗液宏基因组DNA

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural regeneration research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

Why does caloric restriction increase life and healthspan? The ‘clean cupboards’ hypothesis

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National Science review 2020年第7期7卷 1153-1156页

作者： john r.Speakman State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Institute of Biological and EnvironmentalSciences University of Aberdeen CAS Center of Excellence in Animal Evolution and Genetics Kunming Institute of Zoology Chinese Academy of Sciences

The disposable soma hypothesis explanation of the effects of caloric restriction(Cr) on lifespan fails to explain why Cr generates negative impacts alongside the positive effects and does not work in all species. I pr...

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Connecting particle sphericity and circularity

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Particuology 2021年第1期19卷 1-4页

作者： john r.Grace Arian Ebneyamini Department of Chemical&Biological Engineering University of British ColumbiaVancouver V6T 1Z3Canada

Sphericity,a measure of how much a particle’s shape deviates from spherical,is useful as a shape factorwhen characterizing particulate ***,particle surface areas,required when determiningthe sphericity,are very difficult to *** a result,the circularity,derivable from microscopic views,is often measured instead and assumed to be equal to the *** paper shows that the twoquantities are generally not equal for simple non-spherical shapes and provides advice on improving theestimation of sphericity from circularity.

关键词： Non-spherical particles Sphericity Circularity Shape factorsa

Feed- and feed additives-related aspects of gut health and development in weanling pigs

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Journal of Animal Science and Biotechnology 2013年第2期4卷 83-89页

作者： john r Pluske Division of research and Development Murdoch University

The development of new/different management and feeding strategies to stimulate gut development and health in newly-weaned pigs, in order to improve growth performance while minimizing the use of antimicrobial compounds such as antibiotic growth promotants （AGP） and heavy mineral compounds, is essential for the long-term sustainability of the pig industry. Factors including the sub-optimal intake of nutrients and energy, inappropriate microbiota biomass and （or） balance, immature and compromised immune function, and psychosomatic factors caused by weaning can compromise both the efficiency of digestion and absorption and intestinal barrier function through mucosal damage and alteration of tight junction integrity. As a consequence, pigs at weaning are highly susceptible to pathogenic enteric conditions such as post-weaning diarrhea that may be caused by serotypes of enterotoxigenic Escherichia coil Many dietary components, e.g., protein, fiber, feed additives and minerals, are known to influence microbial growth in the gastrointestinal tract that in turn can impact upon pig growth and health, although the relationships between these are sometimes not necessarily apparent or obvious. In a world climate of increased scrutiny over the use of antibiotics per se in pig production, certain feed additives are seen as alternatives/replacements to antibiotics, and have evolved in some cases to have important roles in everyday commercial pig nutrition. Nevertheless and in general, there remains inconsistency and variability in the efficacy of some feed additives and in cases of severe disease outbreaks, for example, therapeutic antibiotics and/or heavy minerals such as zinc oxide （ZnO） are generally relied upon. If feed ingredients and （or） feed additives are to be used with greater regularity and reliability, then it is necessary to better understand the mechanisms whereby antibiotics and minerals such as ZnO influence animal physiology, in conjunction with the use of approp

关键词： Antibiotics Antimicrobials Nutrition Pigs Post-weaning diarrhoea Weaning

Effects of the plenum chamber volume and distributor geometry on fluidized bed hydrodynamics

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Particuology 2010年第1期8卷 2-12页

作者： Kiarash Vakhshouri john r. Grace Department of Chemical and Biological Engineering University of British Columbia

Most hydrodynamic fluidized bed models, including CFD codes, neglect any effects of the plenum chamber volume. Experiments were performed in a 0.13 m ID fluidization column to determine plenum chamber volume effects on fluidized bed hydrodynamics for FCC and glass particles. Two low-pressure-drop distributors were used, one with a single orifice, and the other with 33 orifices and the same total open area as the single orifice. The results show two peaks in the frequency spectra for the single-orifice distributor, one representing bubble eruption at the bed surface and the other of higher frequency corresponding to the bubbling frequency at the distributor. The latter decreased slightly with increasing plenum volume and with increasing bed depth. For the multi-orifice distributor, broad frequency spectra from pressure measurements became narrower and moved towards higher frequency with decreasing plenum volume.

关键词： Fluidization Bubble Distributor Plenum chamber Hydrodynamics Pressure drop

Complementarity of CFD,experimentation and reactor models for solving challenging fluidization problems

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Particuology 2010年第6期8卷 498-500页

作者： john r. Grace Tingwen Li Department of Chemical and Biological Engineering University of British Columbia Vancouver V6T 1Z3 Canada National Energy Technology Laboratory 3610 Collins Ferry Rd Morgantown WV26507 USA

Experimentalists, numerical modellers and reactor modellers need to work together, not only just for validation of numerical codes, but also to shed fundamental light on each other＇s problems and underlying assumptions. Several examples are given, Experimental gas axial dispersion data provide a means of choosing the most appropriate boundary condition （no slip, partial slip or full slip） for particles at the wall of fluidized beds. CFD simulations help to identify how close ＂two-dimensional＂ experimental columns are to being truly two-dimensional and to representing three-dimensional columns. CFD also can be used to provide a more rational means of establishing assumptions needed in the modelling of two-phase fluidized bed reactors, for example how to deal with cases where there is a change in molar flow （and hence volumetric flow） as a result of chemical reactions.

关键词： Fluidization Mixing Computational Fluid dynamics Wall slip reactor modelling Volume change

Falling sperm counts twenty years on： where are we now？

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Asian Journal of Andrology 2013年第2期15卷 204-207,I0006页

作者： r john Aitken Priority research Centre in reproductive Science Discipline of Biological sciences University of Newcastle NSW 2308 Australia

Poor semen quality is an attribute of the human condition that we sharewith our closest primate ancestors and may be part of our evolutionary inheritance. This characteristic may also reflect the lack of selection pressure on male fertility in advanced societies that have gone through the demographic transition. In the future, such trends may be further exacerbated by the widespread use of ArT, which will impair the elimination of low fecundity genotypes from the human gene pool. Environmental pollutants may also be influencing male fertility, however, neither the chemical identity of these factors nor their mechanism-of-action are fully understood.

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Palm oil biodiesel:An assessment of PAH emissions,oxidative potential and ecotoxicity of particulate matter

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Journal of Environmental Sciences 2021年第3期33卷 326-338页

作者： Silvana Arias Francisco Molina john r.Agudelo Grupo de Investigación en Gestión y Modelación Ambiental-GAIA Escuela AmbientalFacultad de IngenieríaUniversidad de Antioquia UdeACalle 70 No.52-21MedellínColombia Departamento de Ingeniería Mecánica Universidad de Antioquia UdeA

This work assessed the impact of fuelling an automotive engine with palm biodiesel(pure,and two blends of 10%and 20%with diesel,B100,B10 and B20,respectively)operating under representative urban driving conditions on 17 priority polycyclic aromatic hydrocarbon(PAH)compounds,oxidative potential of ascorbic acid(OP^(AA)),and ecotoxicity through D aphnia pulex mortality *** diluted with filtered fresh air(WD)gathered in a minitunel,and particulate matter(PM)collected directly from the exhaust gas stream(W/oD)were used for *** showed that PM collecting method significantly impact PAH *** all PAH appeared in both,WD and W/oD,higher concentrations were obtained in the last *** biodiesel concentration in the fuel blend decreased all PAH compounds,and those with 3 and 5 aromatic rings were the most *** biodiesel affected both OP^(AA)and *** B10 and B20 exhibited the same rate of ascorbic acid(AA)depletion,B100 showed significant faster oxidation rate during the first four minutes and oxidized 10%more AA at the end of the test.B100 and B20 were significantly more ecotoxic than *** lethal concentration LC50 for B10 was 6.13 mg/*** was concluded that palm biodiesel decreased PAH compounds,but increased the oxidative potential and ecotoxicity.

关键词： Biodiesel Particulate matter P emissions Oxidative stress Ecotoxicity Daphnia pulex