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Search for microglia-specific peptides:advances in the discovery toolbox

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Neural Regeneration Research 2025年第2期20卷 471-472页

作者： Ivan Sarabia Kyle M.Koss Department of Surgery University of ArizonaTucsonAZUSA

Uncontrolled and chronic inflammatory states in the central nervous system(CNS)are the hallmark of neurodegenerative pathology and every injury or stroke-related *** key mediators of these neuroinflammatory states are glial cells known as microglia,the resident immune cell at the core of the inflammatory event,and astroglia,which encapsulate inflammatory insults in proteoglycan-rich scar *** gliotic scar blocks significant portions of healthy axonal networking,preventing *** most neuroinflammation is exclusively based on the responses of said microglia,their phenotypes are suggested to follow those of macrophages;M1 and M2 are opposites of pro-and ***,microglial phenotypes have been identified to be on an inflammatory spectrum encompassing developmental,homeostatic,and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation.

关键词： inflammation pathology death

MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

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Neural Regeneration Research 2025年第5期20卷 1431-1444页

作者： Yuehua Cui Xiaokuang Ma Jing Wei Chang Chen Neha Shakir Hitesch Guirram Zhiyu Dai Trent Anderson Deveroux Ferguson Shenfeng Qiu Basic Medical Sciences University of Arizona College of Medicine-PhoenixPhoenixAZUSA Department of Medicine University of Arizona College of Medicine-PhoenixPhoenixAZUSA

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse *** have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine *** investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing *** found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection *** findings are further corroborated by increased synaptic activity and transient generation of immature silent *** MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and *** data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult *** findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

关键词： aging circuit connectivity cortical circuits molecular mechanisms neural regeneration neurodegeneration synapses

A simple model for reconstructing geomagnetic field intensity with (10)~Be production rate and its application in Loess studies

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Science China Earth Sciences 2008年第6期51卷 855-861页

作者： J. Warren BECK nsf-ams Laboratory University of Arizona

A simple model for reconstructing the paleomagnetic field intensity with (10)~Be production rate was used for the first time in Loess (10)~Be studies of Luochuan profile. Using the LGM (Last Glacial Maxmium) method, the climatic effects and geomagnetic modulation effects on loess (10)~Be was separated and in turn the 80 ka geomagnetic excursion sequence reconstructed, of which the globally remarkable geomagnetic excursion events such as the Laschamp (42 ka), Mono Lake (32 ka) during the Last Glacial period were revealed and the paleo-geomagnetic intensity curve from Loess (10)~Be over the past 80 ka was quantitatively reconstructed. The reconstructed paleo-intensity fits well with the paleo-intensity curves (SINT200 and NAPIS75), which indicates the significance of global criterion of the (10)~Be paleo- intensity curve and the future direction of loess (10)~Be tracing studies. Results show the irregular vari-ability of the East Asian monsoon precipitation in Loess Plateau is the main cause that has resulted in the ambiguity of the geomagnetic modulation of the (10)~Be record in the loess, and the intrinsic source component of the loess (10)~Be and inherited fraction of magnetic susceptibility (SUS) are characterized by the 'quasi-homogeneous distribution' manner.

关键词： (10)~Be LGM geomagnetic excursion paleointensity quasi-homogeneous distribution

The mean value concept in mono-linear regression of multi-variables and its application to trace studies in geosciences

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Science China Earth Sciences 2007年第12期50卷 1828-1834页

作者： A J T JULL nsf-ams laboratory University of Arizona

The "mean value concept" in a mono-linear regression of multi-variables is *** applications to reconstruction of the past 90-year salinity of the sea surface water in Xisha Islands and to tracing the past 80 ka paleo-geomagnetic events from the Luochuan loess 10Be record are introduced in detail,which show the significance and the potential of the "mean value concept" in geoscience research.

关键词： mean value concept, linear regression, trace, reconstruction

High-resolution peat records for Holocene monsoon history in the eastern Tibetan Plateau

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Science China Earth Sciences 2006年第6期49卷 615-621页

作者： Lars G. Franzen A.J.Tim Jull Department of Earth Sciences Goteborg University P.O. Box 460 SE-405 30 Goteborg Sweden nsf-ams facility University of Arizona Arizona AZ85721 USA

The variations of summer and winter monsoons during the Holocene in theeastern Tibetan Plateau are shown to follow two basic models based on the reliable dating andhigh-resolution monsoon proxies determinations, one being a synchronous model in that both summerand winter monsoons are strengthening or decreasing, and the other to form a complementary *** two different patterns evenly interact with each other on different time scales and togethercompose a complicated monsoon climatic model in this region. The climatic condition integrated bywinter and summer monsoons is synchronous to the global pattern, which also shows the instability ofthe Holocene climate on centennial-millennial timescale. The abrupt monsoon event in about 6.2 kacat. BP is much more severe than that in ca. 8.0 ka cal. BP, which indicates the regional characterof the Asian monsoon and that the Asian monsoon climate is indeed a window on the global climatesystem.

关键词： eastern Tibetan Plateau, Holocene, winter and summer monsoons, asynchronous, peat, climate instability.

Biological records of paleoclimate and paleoenvironment changes from Guanzhong area, Shaanxi Province during the last glacial maximum

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Chinese Science Bulletin 2000年第9期45卷 853-857页

作者： J.Head A.J.T.Jull State Key Laboratory of Loess and Quaternary Geology Xi'an 710054ChinaNSF-AMS Facility Department of PhysicsUniversity of ArizonaAZ 85721USA

We have collected a suite of Paleoloxodon naumanni-Coelodonta antiquitatis fossils from a river terrace profile between Xi’an and Xianyang cities in Guanzhong Area, Shaanxi Province. A detailed examination of the fossils, together with 14C determinations and pollen analyses, have enabled us to reconstruct preliminary features of climate and environment changes and their evolutionary processes, within the last glacial maximum (LGM): about 20 ka ago, the climate was basically cool and wet, and was favourable for the existence of Paleoloxodon naumanni-Coelodonta antiquitatis fauna. This was followed by a cold, dry phase which was no longer suitable for this type of faunal suite, causing the death of a large number of mammalian assemblages. The available evidence indicates the existence of cold-dry and cool-wet climate and environment fluctuations during the LGM. The cool-wet stage within the LGM reflects a Heinrich event occurring in the high latitude areas, proving the existence of a teleconnection

关键词： Guanzhong of Shaanxi Province Paleoloxodon naumanni-Coelodonta antiguitatis fauna last glacial maximum paleomonsoon precipitation.

Correlation of climatic events between East Asia and Norwegian Sea during last deglaciation

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Science China Earth Sciences 1997年第5期40卷 496-501页

作者：周卫建安芷生 S.C.Porter D.Donahue A.J.T.Jull Department of Geology Northwest University Xi'an 710069 China State Key Laboratory of Loess and Quaternary Geology Chinese Academy of Sciences Xi'an 710054 China Quaternary Research Center University of Washington Seattle 98195 USA nsf-ams-facility University of Arizona Tucson 85721 USA

Using a high resolution 14C chronology, Sl C values and organic carbon content, from loess/paleosol and peat profiles in China, we can demonstrate century scale warm-cold East Asian monsoon paleoclimatic fluctuation events and significant precipitation variability within the last deglaciation. The major climatic events recognized are the Boiling (1 300-12 500 a B. P.), Older Dryas (12 500-11 750 a B. P. ), Allerod (11 750-11 200 a B. P.) and Younger Dryas (11 200-10 000 a B.P. ). The stratigraphic structure of the last deglaciation sediments is characterized by frequent changes in sedimentation phases reflecting climatic instability. These high frequency, rapid climatic events can correlate with fluctuations recorded by sea surface temperatures in the Norwegian Sea. This indicates a pale-oclimate teleconnection between polar, high latitude areas and East Asian monsoon areas through westerlies and the related atmospheric pressure system.

关键词： last rieglaciation East Asian monsoon paleoclimatic fluctuation loess-paleosol

Assembly of multicomp on ent structures from hundreds of micron-scale building blocks using optical tweezers

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Microsystems & Nanoengineering 2021年第3期7卷 163-171页

作者： Jeffrey E.Melzer Euan McLeod Wyant College of Optical Sciences The University of ArizonaTucsonArizona85721USA

The fabrication of three-dimensional(3D)microscale structures is critical for many applications,including strong and lightweight material development,medical device fabrication,microrobotics,and photonic *** 3D microfabrication has seen progress over the past decades,complex multicomponent integration with small or hierarchical feature sizes is still a *** this study,an optical positioning and linking(OPAL)platform based on optical tweezers is used to precisely fabricate 3D microstructures from two types of micron-scale building blocks linked by biochemical interactions.A computer-controlled interface with rapid on-the-fly automated recalibration routines main tains accuracy eve n after placi ng many buildi ng *** achieves a 60-nm positional accuracy by optimizing the molecular functionalization and laser power.A two-component structure consisting of 4481-pm building blocks is assembled,representing the largest number of building blocks used to date in 3D optical tweezer *** optical tweezers have previously been used for microfabrication,those results were generally restricted to single-material structures composed of a relatively small number of larger-sized building blocks,with little discussion of critical process *** is anticipated that OPAL will enable the assembly,augmentation,and repair of microstructures composed of specialty micro/nanomaterial building blocks to be used in new photonic,microfluidic,and biomedical devices.

关键词： hundreds blocks sized

Building bioorthogonal click-release capable artificial receptors on cancer cell surface for imaging,drug targeting and delivery

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Acta Pharmaceutica Sinica B 2023年第6期13卷 2736-2746页

作者： Jing Chen Peng Ji Giri Gnawali Mengyang Chang Feng Gao Hang Xu Wei Wang Department of Pharmacology and Toxicology University of ArizonaTucsonAZ 85721USA Department of Chemistry and Biochemistry University of ArizonaTucsonAZ 85721USA BIO5 Institute and University of Arizona Cancer CenterUniversity of ArizonaTucsonAZ 85721USA

The current targeting drug delivery mainly relies on cancer cell surface ***,in many cases,binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not *** from conventional targeting strategies,we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans.A new tetrazine(Tz)functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as“overexpressed”biomarker through a metabolic glycan *** from the reported bioconjugation for drug targeting,the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release *** studies have demonstrated that the new drug targeting strategy enables local activation of prodrug,which ultimately leads to effective and safe cancer therapy.

关键词： Artificial receptor Click and release Local activation Protein degradation