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Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

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Neural Regeneration Research 2025年第7期20卷 1991-1992页

作者： Fengwen Huang stephen Temitayo Bello Department of Neuroscience City University of Hong KongKowloon TongHong Kong Special Administrative RegionChina Center for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong Special Administrative RegionChina

Spatial memory is crucial for survival within external surroundings and wild *** hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and *** neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal ***(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target *** instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety ***,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

关键词： abundant functions modulator

Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date

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World Journal of Clinical Cases 2015年第8期3卷 694-704页

作者： Kyle Crassini stephen p.mulligan O Giles Best Northern Blood Research Centre and CLL Australian Research Consortium Kolling Institute of Medical Research Royal North Shore Hospital

Chronic lymphocytic leukemia(CLL) is the most common leukemia in the western world. Despite significantadvances in therapy over the last decade CLL remains incurable. Current front-line therapy often consists of chemoimmunotherapy-based regimens, most commonly the fludarabine, cyclophosphamide plus rituximab combination, but rates of relapse and refractory disease are high among these patients. Several key signaling pathways are now known to mediate the survival and proliferation of CLL cells in vivo, the most notable of which are the pathways mediated by the B-cell receptor(BCR) and cytokine receptors. A better understanding of the pathogenesis of the disease, the underlying biology of the CLL-cell and the roles of the tumour microenvironment has provided the rationale for trials of a range of novel, more targeted therapeutic agents. In particular, clinical trials of ibrutinib and idelalisib, which target the Brutons tyrosine kinase and the delta isoform of phosphoinositol-3 kinase components of the BCR signaling pathway respectively, have shown extremely promising results. Here we review the current literature on the key signaling pathways and interactions of CLL cells that mediate the survival and proliferation of the leukemic cells. For each we describe the results of the recent clinical trials and in vitro studies of novel therapeutic agents.

关键词： Chronic lymphocytic leukemia Therapy Microenvironment Leukemia Novel

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

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Neural Regeneration Research 2025年第11期20卷 3063-3075页

作者： stephen Vidman Yee Hang Ethan Ma Nolan Fullenkamp Giles W.plant Department of Neuroscience Ohio State UniversityColumbusOHUSA

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative *** the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained *** work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as *** embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns *** barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem *** advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal *** precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed *** the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma *** of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of *** the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor ***,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support ***,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for *** to a clinical setting wi

关键词： axon regeneration central nervous system regeneration induced pluripotent stem cells neurotrauma regenerative medicine spinal cord injury stem cell therapy

Improving the wind and temperature measurements of an airborne meteorological measuring system

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Journal of Zhejiang University-Science A(Applied physics & Engineering) 2012年第10期13卷 723-746页

作者： stephen FOSTER p.W.CHAN Aventech Research Inc. BarrieON L4N 2E3Canada Hong Kong Observatory KowloonHong KongChina

The Aircraft Integrated Meteorological Measuring System 20 Hz(AIMMS-20) has been used by the Hong Kong Observatory(HKO),China in data collection for tropical cyclone situations over the South China Sea and windshear and turbulence measurement at the Hong Kong International Airport(HKIA).This paper discusses possible methods for further enhancing the quality of the wind and temperature measurements from the *** wind measurement,the enhancement methods include:error modelling of the accelerometer(e.g.,bias offset and cross-axis rate sensitivity),global positioning system(GpS) phase lag consideration,better representation of the inertial measurement unit(IMU) velocity based on the GpS velocities and considering their location differences,consideration of the slower update of GpS velocity,and wing *** temperature measurement,the methods include the consideration of the temperature sensor response and the sensor housing *** results of typical flights using AIMMS-20 show that the accuracy of the wind and temperature data could be improved by 20%-30%.Though the discussion in the present paper is related mainly to a specific meteorological measuring system on a particular aircraft,the techniques so employed should be a useful reference for similar systems installed on other aircraft.

关键词： Airborne meteorological measurements Kalman filter Comparison with radiosonde measurement

The trajectory of hybrid and hydrogen technologies in North American heavy haul operations

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Railway Engineering Science 2021年第3期29卷 233-247页

作者： Kevin Oldknow Kyle mulligan Gordon McTaggart-Cowan Simon Fraser University SurreyBCCanada Canadian pacific CalgaryABCanada

The central aim of this paper is to provide an upto-date snapshot of hybrid and hydrogen technology-related developments and activities in the North American heavy haul railway setting,placed in the context of the transportation industry more *** overview of relevant alternative propulsion technologies is provided,including a discussion of applicability to the transportation sector in general and heavy haul freight rail *** is followed by a discussion of current developments and research in alternative and blended fuels,discussed again in both general and specific *** factors and technical considerations for heavy haul applications are reviewed,followed by a discussion of non-technical and human factors that motivate a move toward clean energy in North American Heavy Haul ***,current project activities are described to provide a clear understanding of both the status and trajectory of hybrid and hydrogen technologies in the established context.

关键词： Transportation propulsion Hydrogen Hybrid Alternative fuels

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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Neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： Siva S.V.p.Sakamuri Anil Sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi pradeepkiran priyanka Rawat Arubala p.Reddy Erika Orlov pHemachandra Reddy Department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA Department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA Department of pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA Department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA Department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA Department of public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAp-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

Geologic field evidence for non-lithostatic overpressure recorded in the North American Cordillera hinterland,northeast Nevada

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Geoscience Frontiers 2022年第2期13卷 471-490页

作者： Andrew V.Zuza Drew A.Levy Suzanne R.mulligan Nevada Bureau of Mines and Geology University of NevadaRenoNV 89557USA Department of Geoscience University of NevadaLas VegasNV 89154USA

There is a long-standing discrepancy for numerous North American Cordillera metamorphic core complexes between geobarometric pressures recorded in the exhumed rocks and their apparent burial depths based on palinspastic reconstructions from geologic field *** particular,metamorphic core complexes in eastern Nevada are comprised of well-documented~12-15 km thick Neoproterozoic-paleozoic stratigraphy of Laurentia’s western passive margin,which allows for critical characterization of field *** this contribution we focus on the Ruby Mountain-East Humboldt Range-Wood Hills-pequop Mountains(REWp)metamorphic core complex of northeast Nevada to explore reported peak pressure estimates versus geologic field relationships that appear to prohibit deep *** high pressure estimates of 6-8 kbar(23-30 km depth,if lithostatic)from the lower section of the Neoproterozoic-paleozoic passive margin sequence require burial and or repetition of the passive margin sequence by 2-3×stratigraphic *** observations from the least migmatized and/or mylonitized parts of this complex,including field observations,a transect of peak-temperature(T_(p))estimates,and critical evaluation of proposed thickening/burial mechanisms cannot account for such deep *** Neoproterozoic-Cambrian(€)rocks part of a continuous stratigraphic section that transitions~8 km upsection to unmetamorphosed permian strata that were not buried,we obtained new quartz-in-garnet barometry via Raman analysis that suggest pressures of~7 kbar(~26 km).A T_(p)traverse starting at the same basal€rocks reveals a smooth but hot geothermal gradient of≥40℃/km that is inconsistent with deep *** observation is clearly at odds with thermal gradients implied by high p-T estimates that are all≤25℃/*** similar discrepancies between pressure estimates and field observations have been discussed for the northern Snake Range metamorphic core complex,~200 km to the *** argue that

关键词： Non-lithostatic pressure Tectonic overpressure North American Cordillera Ruby Mountain-East Humboldt Range peak temperature Geothermal gradient

potential hydrodynamic origin of frictional transients in sliding mesothelial tissues

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Friction 2013年第2期1卷 163-177页

作者： stephen H.LORING James p.BUTLER Department of Anesthesia Critical Care and Pain MedicineBeth Israel Deaconess Medical Center and Harvard Medical SchoolBoston MA 02215USA Department of Medicine Division of Sleep MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBoston MA 02215USA

Steady-state and transient variations in frictional force observed in tribological experiments of mesothelial tissues sliding in lubricant were analyzed with a mathematical model to test the hypothesis that such phenomena are manifestations of elastohydrodynamic lubrication and,importantly,do not require physical contact between the sliding *** model incorporates three phenomena characteristic of elastohydrodynamic lubrication:thinning of the liquid layer between sliding surfaces under a normal load(“squeeze-out”),thickening of the liquid layer due to hydrodynamic pumping,and smoothing of the elastic surfaces caused by hydrodynamic pressure *** in soft mesothelial tissues sliding in lubricant showed variations in steady state friction with velocity,load,and lubricant *** non-steady sliding,the decay rate of frictional transients at the start of rotation varied with velocity,the amplitudes of these transients varied with the preceding periods without rotation,and frictional force varied during sinusoidal *** simulations were qualitatively similar to experimental results,supporting these *** lubricant viscosity increased lubricating layer thickness and lowered friction at low speeds and increased friction at high speeds,supporting hydrodynamic *** conclude that the frictional variations seen with sliding mesothelial tissues are consistent with elastohydrodynamic lubrication without contact between the sliding surfaces.

关键词： pleural space breathing pericardium lubrication model