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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

Fatigue behavior of high-entropy alloys： A review

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Science China(Technological Sciences) 2018年第2期61卷 168-178页

作者： CHEN PeiYong LEE Chanho WANG Shao-Yu SEIFI Mohsen lewandowski john j DAHMEN Karin A jIA HaoLing XIE Xie CHEN BiLin YEH jien-Wei TSAI Che-Wei YUAN Tao LIAW Peter K Department of Materials Science and Engineering The University of TennesseeKnoxville 37996，USA Department of Materials Science and Engineering Case Western UniversityCleveland 44106USA Department of Physics University of IllinoisUrbana 61801USA Department of Materials Science and Engineering 'National' Tsing Hua UniversityHsinchu 30013，Taiwan，China Department of Industry and System Engineering Ohio UniversityAthens 45701，USA

Fatigue failures cost approximately 4% of the United States' gross domestic product(GDP). The design of highly fatigue-resistant materials is always in demand. Different from conventional strategies of alloy design, high-entropy alloys(HEAs) are defined as materials with five or more principal elements, which could be solid solutions. This locally-disordered structure is expected to lead to unique fatigue-resistant properties. In this review, the studies of the fatigue behavior of HEAs during the last five years are summarized. The four-point-bending high-cycle fatigue coupled with statistical modelling, and the fatigue-crack-growth behavior of HEAs, are reviewed. The effects of sample defects and nanotwins-deformation mechanisms on four-point-bending high-cycle fatigue of HEAs are discussed in detail. The influence of stress ratio and temperature on fatigue-crack-growth characteristics of HEAs is also discussed. HEAs could exhibit comparable or greater fatigue properties, relative to conventional materials. Finally,the possible future work regarding the fatigue behavior of HEAs is suggested.

关键词： high-entropy alloys fatigue behaviour statistical modelling fatigue crack growth

铝合金材料AA-6061-T6和AA-6061-OA的动态拉伸力学性能(英文)

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实验力学 2007年第3期22卷 305-313页

作者：唐欣 Vikas Prakash john lewandowski 凯斯西部保留地大学力学与航空工程系凯斯西部保留地大学材料科学与工程系

铝合金材料蜂窝夹层板结构具有在较低体重情况下的高硬度和高抗冲击性能力。近年来许多关于其在低应变率下冲击能量吸收性质的文献纷纷涌现,但是对于其在高应变率下的能量吸收力学性能的研究却非常贫乏。为了更好地研究铝合金材料蜂窝... 详细信息

铝合金材料蜂窝夹层板结构具有在较低体重情况下的高硬度和高抗冲击性能力。近年来许多关于其在低应变率下冲击能量吸收性质的文献纷纷涌现,但是对于其在高应变率下的能量吸收力学性能的研究却非常贫乏。为了更好地研究铝合金材料蜂窝夹层板结构在高应变率下的能量吸收力学性能,其结构组成材料本身的动态力学性能必须首先得到充分研究。本文介绍和总结了铝合金材料AA-6061的两种热处理成品,T6与OA,在室温(24℃)与低温( -170℃)下的动态拉伸力学性能。在本研究中,霍普金生拉伸杆被应用,拉伸应变率为103每秒。

关键词：铝合金材料AA-6061-T6/OA 室温(24℃)与低温(-170℃)试验霍普金生拉伸杆高应变率

Effects and mechanisms of silibinin on human hepatoma cell lines

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World journal of Gastroenterology 2007年第40期13卷 5299-5305页

作者： john j Lah Division of Gastroenterology University of CaliforniaIrvine Medical Center101 The City DriveBuilding 53Suite 113OrangeCA 92868United States

AIM： To investigate in vitro effects and mechanisms of silibinin on hepatocellular carcinoma （HCC） cell growth, METHODS： Human HCC cell lines were treated with different doses of silibinin. The effects of silibinin on HCC cell growth and proliferation, apoptosis, cell cycle progression, histone acetylation, and other related signal transductions were systematically examined. RESULTS： We demonstrated that silibinin significantly reduced the growth of HUH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells. Silibinin-reduced HuH7 cell growth was associated with significantly up- regulated p21/CDK4 and p27/CDK4 complexes, down- regulated Rb-phosphorylation and E2F1/DP1 complex. Silibinin promoted apoptosis of HuH7 cells that was associated with down-regulated survivin and upregulated activated caspase-3 and -9. Silibinin＇s antiangiogenic effects were indicated by down-regulated metalloproteinase-2 （MMP2） and CD34. We found that silibinin-reduced growth of HuH7 cells was associated with increased activity of phosphatase and tensin homolog deleted on chromosome ten （PTEN） and decreased p-Akt production, indicating the role of PTEN/ PI3K/Akt pathway in silibinin-mediated anti-HCC effects. We also demonstrated that silibinin increased acetylation of histone H3 and H4 （AC-H3 and AC-H4）, indicating a possible role of altered histone acetylation in silibininreduced HCC cell proliferation. CONCLUSION： Our results defined silibinin＇s in vitro anti-HCC effects and possible mechanisms, and provided a rationale to further test silibinin for HCC chemoprevention.

关键词： Hepatocellular carcinoma HuH7 cells Silibinin Chemoprevention Cell cycle Cell cycleprogression Apoptosis Acetylation of histone

Identification of the preferentially targeted proteins by carbamylation during whole lens incubation by using radio-labelled potassium cyanate and mass spectrometry

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International journal of Ophthalmology(English edition) 2010年第2期3卷 104-111页

作者： john j Harding Nuffield Laboratory of Ophthalmology University of OxfordJohn Radcliffe HospitalHeadingtonOxfordUK

AIMTo attempt to identify the primary targets of carbamylation in bovine lenses incubated under physiological condition.

关键词： carbamylation cyanate cataract identification lens mass spectrometry post-translational modification ξ-crystallin

Field observations of putative bone-based fluorescence in a gecko

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Current Zoology 2018年第3期64卷 319-320页

作者： john j, SLOGGETT Maastricht Science Programme Maastricht University P.O. Box 616 6200 MD Maastricht The Netherlands

A diversity of animals are biofluorescent, absorbing shortwavelength electromagnetic radiation, and re-emitting it at longer wavelengths, giving a distinctive pattern （Lagorio et al. 2015）. Among terrestrial organisms, biofluorescence has been commonly recorded in arthropods, but rarely from vertebrates （Lagorio et al. 2015）. It has long been known from parrots （Hausmann et al. 2003） and has recently been recorded from a frog （Taboada et al. 2017） and from chameleons （Chamaeleonidae： Protzel et al. 2018）.

关键词： biofluorescence bone Chondrodactylus bibronii Gekkonidae signaling Squarnata

Apoptosis and DNA damage in human spermatozoa

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Asian journal of Andrology 2011年第1期13卷 36-42页

作者： R john Aitken Adam j Koppers ARC Centre of Excellence in Biotechnology and Development Priority Research Centre in Reproductive Science Discipline of Biological Sciences School of Environmental and Life Sciences University of Newcastle Callaghan NSW 2308 Australia Department of Anatomy and Developmental Biology School of Biomedical Sciences Monash University Clayton VIC 3800 Australia

DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apeptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.

关键词： apoptosis DNA damage oxidative stress spermatozoa

New technologies in the gastrointestinal clinic and research: Impedance and high-resolution manometry

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World journal of Gastroenterology 2009年第2期15卷 131-138页

作者： john E Pandolfino Peter j Kahrilas Division of Gastroenterology Department of Medicine Northwestern University Feinberg School of Medicine Suite 1400 Chicago Illinois 60611 United States

The last five years have been an exciting time in the study of esophageal motor disorders due to the recent advances in esophageal function testing. New technologies have emerged, such as intraluminal impedance, while conventional techniques, such as manometry, have enjoyed many improvements due to advances in transducer technology, computerization and graphic data presentation. While these techniques provide more detailed information regarding esophageal function, our understanding of whether they can improve our ability to diagnose and treat patients more effectively is evolving. These techniques are also excellent research tools and they have added substantially to our understanding of esophageal motor function in dysphagia. This review describes the potential benefits that these new technologies may have over conventional techniques for the evaluation of dysphagia.

关键词： Dysphagia, Multichannel intraluminal Impedance Bolus transit High-resolution manometry Esophagogastric junction Achalasia

Particulate matter and metals partitioning in highway rainfall-runoff

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Frontiers of Environmental Science & Engineering 2010年第1期4卷 35-46页

作者： Gaoxiang YING john j.SANSALONE Environmental Engineering Sciences University of Florida108 Black HallGainesvilleFL 32611USA

This study investigated the particulate matter(PM)and metals in highway dry deposition and rainfallrunoff as a function of hydrologic transport and settling on an event *** were differentiated as mass-limited(ML)and flow-limited(FL).Results indicate that unique and separate suspended sediment concentration(SSC)relationships with turbidity occurred for ML and FL *** minutes of quiescent settling produced a single SSC-turbidity relationship for all *** events transport higher proportions of settleable and sediment PM while FL events transported relatively higher suspended *** batch clarification with one hour of settling,ML events had generally higher treatment efficiencies compared to FL events for the same settling *** dry deposition PM was hetero-disperse and coarse(d50 m=304µm).Results indicate that the acidic rainfall is not a significant contributor to metals in runoff but is capable of leaching metals from dry deposition PM into *** in retained runoff resulted in a particulate-bound predominance for most metals except Ca and *** the finer fraction of dry deposition PM(75µm).

关键词： stormwater particulate matter(PM) turbidity suspended sediment concentration(SSC) unit operations metals dry deposition acid rain