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Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation

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Bone research 2022年第4期10卷 826-837页

作者： Yugo Morita Motoo Saito Javier rangel-Moreno Anthony M.Franchini john r.owen john C.Martinez john L.Daiss Karen L.de Mesy Bentley Stephen L.Kates Edward M.Schwarz Gowrishankar Muthukrishnan Center for Musculoskeletal research University of Rochester Medical CenterRochesterNYUSA Division of Allergy Immunology and RheumatologyDepartment of MedicineUniversity of Rochester Medical CenterRochesterNYUSA Department of Environmental Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Orthopedic Surgery Virginia Commonwealth UniversityRichmondVAUSA Department of Orthopedics University of Rochester Medical CenterRochesterNYUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA

Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial,and its role in patients with *** osteomyelitis is *** address this knowledge gap,we completed a clinical study and observed elevated serum IL-27 levels(20-fold higher,Pred with healthy ***,IL-27 serum levels were 60-fold higher in patients immediately following septic death than in uninfected patients(Prole of *** test this hypothesis,we evaluated *** osteomyelitis in WT and IL-27rα^(−/−)mice with and without exogenous IL27 induction by intramuscular injection of rAAV-IL-27p28 or rAAV-GFP,*** found that IL-27 was induced at the surgical site within 1 day of *** infection of bone and was expressed by M0,M1 and M2 macrophages and osteoblasts but not by ***,exogenous IL-27p28(~2 ng·mL^(−1) in serum)delivery ameliorated soft tissue abscesses and periimplant bone loss during infection,accompanied by enhanced local IL-27 expression,significant accumulation of rOrγt^(+)neutrophils at the infection site,a decrease in rANK^(+) cells,and compromised osteoclast *** effects were not observed in IL-27rα^(−/−)mice compared with WT mice,suggesting that IL-27 is dispensable for immunity but mediates redundant immune and bone cell functions during *** vitro studies and bulk rNA-seq of infected tibiae showed that IL-27 increased nos1,nos2,il17α,il17f,and rorc expression but did not directly stimulate ***,these results identify a novel phenomenon of IL-27 expression by osteoblasts immediately following *** infection of bone and suggest a protective role of systemic IL-27 in osteomyelitis.

关键词： abscess protective immunity

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A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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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

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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

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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

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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

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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

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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

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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

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