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Amyloid-β-induced disruption of axon-initial-segment mitochondria localization:consequences for TAU missorting in Alzheimer's disease pathology

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Neural Regeneration Research 2025年第5期20卷 1407-1408页

作者： Daniel adam Felix Langerscheidt Hans Zempel Institute of Human Genetics University Hospital CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany

TAU is a neuronal microtubule-associated protein preferentially located in *** a battery of neurodegenerative diseases termed"tauopathies,"including Alzheimer's disease (AD),TAU is missorted and abnormally phosphorylated,leading to filamentous accumulations of hyperphosphorylated TAU,a pathological hallmark and potential disease driver of AD and related tauopathies (Zempel,2024).

关键词： Alzheimer tau diseases

A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan Cuccia Rachael Coates Blake Nassar Ethan Littlefield Elizabeth C.Martin adam T.Melvin Cain Department of Chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of Chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural Engineering Louisiana State UniversityBaton RougeLA 70803USA Department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to *** is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause *** this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(Fss)found in human vasculature was designed and *** device provides a platform to evaluate the effects of Fss on MCF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the *** of the effects of Fss on MCF-7 cells was carried out utilizing two approaches:single cell analysis and bulk *** single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an Fss magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell *** understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKT,and JAK/*** demonstrated that after shearing the cells phosphorylation of p-AKT,p-mTOR,and p-sTAT3 were ***,there was no change in p-ERK1/*** is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were *** together these results demonstrate that Fss can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer *** findin

关键词： fluid breast estrogen

Multinuclear MR and MRI study of lithium-ion cells using a variable field magnet and a fixed frequency RF probe

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Magnetic Resonance Letters 2024年第1期4卷 10-20页

作者： Andrés Ramírez Aguilera Florin Marica Kevin J.sanders Md Al Raihan C.adam Dyker Gillian R.Goward Bruce *** UNB MRI Centre Department of PhysicsUniversity of New BrunswickFrederictonNew BrunswickE3B 5A3Canada Department of Chemistry McMaster UniversityHamiltonOntarioL8S 4L8Canada Department of Chemistry University of New BrunswickFrederictonNew BrunswickE3B 5A3Canada

An exploratory multinuclear magnetic resonance(MR)and magnetic resonance imaging(MRI)study was performed on lithium-ion battery cells with ^(7)Li,^(19)F,and ^(1)H measurements.A variable field superconducting magnet with a fixed frequency parallel-plate radiofrequency(RF)probe was employed in the *** magnetic field was changed to set the resonance frequency of each nucleus to the fixed RF probe frequency of 33.7 *** cartridge-like lithium-ion cells,with graphite anodes and LiNi_(0.5)Mn_(0.3)Co_(0.2)O_(2)(NMC)cathodes,were *** cell was pristine,and one was charged to a cell voltage of 4.2 *** results presented demonstrate the great potential of the variable field magnet approach in multinuclear measurement of lithium-ion *** methods open the door for developing faster and simpler methods for detecting,quantifying,and interpreting MR and MRI data from lithium-ion and other batteries.

关键词： Multinuclear MR/MRI Variable field magnet Lithium-ion battery Parallel-plate rf probe

Detection and clearance in Alzheimer’s disease: leading with illusive chemical, structural and morphological features of the targets

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Neural Regeneration Research 2024年第3期19卷 497-498页

作者： Luís Gales i3s−Instituto de Investigação e Inovação em saúde Rua Alfredo AllenPortoPortugal(Gales L)IBMC−Instituto de Biologia Molecular e CelularUniversidade do PortoRua Alfredo AllenPortoPortugal ICBAs−Instituto de Ciências Biomédicas Abel salazar Rua de Jorge Viterbo FerreiraPortoPortugal

Highly specific interactions between biomolecules,such as antigen-antibody,protein-ligand,or nucleic acid base pair complementary are on the basis of the organization of complex *** same principles may be tentatively used in molecular medicine for diagnosis and therapeutics.A molecule can be designed to selectively bind a protease and thereby inhibit the production of a peptide that forms toxic aggregates in the brain or an antibody may be produced to bind specifically to that peptide for detection or clearance ***,interference in biological systems is not that *** a start there is the inhibition of the physiological role of the protease;moreover,several cleavage fragments may be produced,which may continue to diverge due to putative post-translational modification and self-assembly processes,hiding the toxic target in a“soup”of peptide species varying in size,structure and chemical composition.A perspective of the current status and challenges in targeting peptide species for diagnosis and treatment in the context of Alzheimer’s disease is given.

关键词： Alzheimer diagnosis thereby

Photometric and spectroscopic study of Ten Low Mass Ratio Contact Binary systems: Orbital stability, O'Connell Effect and Infrared Calcium Line Filling

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Research in Astronomy and Astrophysics 2024年第8期24卷 214-224页

作者： surjit s.Wadhwa adam Popowicz Raúl Michel Petar Kosti? Oliver Vince Nick F.H.Tothill Ain Y.De Horta Miroslav D.Filipovi? school of science Western Sydney University Department of Electronics Electrical Engineering and MicroelectronicsSilesian University of Technology Instituto de Astronomía Astronomical Observatory

Low mass ratio contact binary systems are more likely to have unstable orbits and potentially *** addition,such systems exhibit characteristics such as starspots and high energy emissions (UV) suggestive of chromospheric and magnetic *** curve modeling of ten contact binary systems is *** were found to be of extreme low mass ratio ranging from 0.122 to 0.24 and three were found to be potentially unstable and possible merger *** of the infrared calcium absorption lines is a marker of increased chromospheric *** use the available Large sky Area Multi-Object Fiber spectroscopic Telescope spectra along with matched standard spectra (broadened for rotation) to measure the excess filling of the central core depression flux of the two main infrared calcium absorption linesλ8542 andλ*** find that all reported contact binaries have excess filling of the core flux in the infrared calcium *** of the systems reported were also observed by the Galaxy Evolution Explorer mission and we find that all three have features of excess ultraviolet emissions further adding evidence for increased chromospheric activity in low mass ratio contact *** of both orbital stability and absorption line filling is dependent on the determination of geometric and absolute parameters from light curve *** an insignificant number of contact binary light curves exhibit the O’Connell effect,usually attributed to *** discuss the inclusion of starspots in light curve solutions and how they influence the geometric and absolute parameters.

关键词： (stars:) binaries: eclipsing stars: chromospheres techniques: photometric

seroprevalence survey of HIV and Hepatitis B Virus and Behavioral Characteristics among Heavy Truck Drivers along Port sudan-Khartoum Highways

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Open Journal of Medical Microbiology 2024年第1期14卷 11-22页

作者： sara s. Osman adam A. Mattar Omnia M. Hamid Faculty of Public Health Alzaiem Alazhari University Khartoum Sudan Faculty of Medical Laboratory sciences University of Medical Sciences & Technology Khartoum Sudan

The prevalence of human immunodeficiency virus (AIDs) and hepatitis B virus among heavy truck drivers and their assistants has been well documented globally in correlation with their behavioral characteristics. The present study aimed to screen for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and behavioral characteristics among heavy truck drivers in Port sudan. A cross-sectional study was conducted on 274 heavy truck drivers and their assistants who used the highway Port sudan-Khartoum in Port sudan city during 2019-2021. Data on behavioral characteristics and substance use habits were collected using a structured questionnaire, and an ELIsA test was used to screen for HIV and HBV infections in the study participants. The chi-square test, odds ratio, and confidence intervals were used to find the association between behavioral characteristics and seropositive HIV/HBV. Of the 274 enrolled participants, the seroprevalence rates of HIV were 2.7% and HBV was 23.7%. Ninety-four (34.3%) of them had a history of high-risk sexual behavior outside of marriage;only two (0.7%) used condoms;14.2% of participants reported alcohol use;and 1.1% reported drug use. Univariate analysis revealed that having a sex history outside of marriage with ≥1 sex partner and never using a condom with a spouse or casual partner were significant risk factors for HIV and HBV among drivers. Fortunately, we found that most of the drivers reported low alcohol and drug use. Concerning this study, the seroprevalence of HIV and HBV is highly associated with a history of having sex outside of marriage and sexual behavior among truck drivers and assistances. Additional studies are needed to further investigate other sTIs and behavioral characteristics associated with factors in truck drivers/assistance in different truck stop regions in sudan.

关键词： sexual Transmitted Infection Port sudan Truck Drivers/Assistance

Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing

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Cellular & Molecular Immunology 2024年第4期21卷 362-373页

作者： Zeguang Wu Qiezhong Lamao Meichao Gu Xuanxuan Jin Ying Liu Feng Tian Ying Yu Pengfei Yuan shuaixin Gao Thomas s.Fulford adam P.Uldrich Catherine C.L Wong Wensheng Wei Biomedical Pioneering Innovation Center Peking-Tsinghua Center for Life SciencesPeking University Genome Editing Research CenterState Key Laboratory of Protein and Plant Gene ResearchSchool of Life SciencesPeking University100871BeijingChina EdiGene Inc. Life Science ParkChangping District102206BeijingChina Center for Precision Medicine Multi-Omics Research Peking University Health Science CenterPeking University100191BeijingChina Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity The University of MelbourneParkvilleVIC3010Australia Cancer Immunology Program Peter MacCallum Cancer CentreMelbourneVICAustralia state Key Laboratory for Complex Severe and Rare DiseasesClinical Research InstitutePeking Union Medical College HospitalChinese Academy of Medical Science&Peking Union Medical CollegePeking-Tsinghua Center for Life Sciences100871BeijingChina

Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate *** our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRIsPR screening of cancer *** found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T *** coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX ***,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer *** our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T ***,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.

关键词： Butyrophilin Vγ9Vδ2 T-cell Cancer-specific immune evasion Glutaminyl-peptide cyclotransferase-like Pyrophosphate metabolite Immunotherapy

Machine learning-guided accelerated discovery of structure-property correlations in lean magnesium alloys for biomedical applications

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Journal of Magnesium and Alloys 2024年第6期12卷 2267-2283页

作者： sreenivas Raguraman Maitreyee sharma Priyadarshini Tram Nguyen Ryan McGovern Andrew Kim adam J.Griebel Paulette Clancy Timothy P.Weihs Department of Materials science and Engineering Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A Hopkins Extreme Materials Institute Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A Department of Chemical and Biomolecular Engineering Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A Translational Tissue Engineering Center Johns Hopkins School of Medicine400 N BroadwayBaltimore21231MDU.S.A Department of Biomedical Engineering Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A Research and Development Fort Wayne Metals Research ProductsLLC9609 Ardmore AveFort Wayne46809INU.S.A Department of Mechanical Engineering Johns Hopkins University3400 N Charles StBaltimore21218MDU.S.A

Magnesium alloys are emerging as promising alternatives to traditional orthopedic implant materials thanks to their biodegradability,biocompatibility,and impressive mechanical ***,their rapid in-vivo degradation presents challenges,notably in upholding mechanical integrity over *** study investigates the impact of high-temperature thermal processing on the mechanical and degradation attributes of a lean Mg-Zn-Ca-Mn alloy,*** rapid,cost-efficient characterization methods like X-ray diffraction and optical microscopy,we swiftly examine microstructural changes post-thermal *** Pearson correlation coefficient analysis,we unveil the relationship between microstructural properties and critical targets(properties):hardness and corrosion ***,leveraging the least absolute shrinkage and selection operator(LAssO),we pinpoint the dominant microstructural factors among closely correlated *** findings underscore the significant role of grain size refinement in strengthening and the predominance of the ternary Ca_(2)Mg_(6)Zn_(3)phase in corrosion *** suggests that achieving an optimal blend of strength and corrosion resistance is attainable through fine grains and reduced concentration of ternary *** thorough investigation furnishes valuable insights into the intricate interplay of processing,structure,and properties in magnesium alloys,thereby advancing the development of superior biodegradable implant materials.

关键词： Magnesium alloys Machine learning Corrosion Mechanical properties Rapid characterization

Astrophysical s-factor and reaction rate for 15N(p,γ)16O within the modified potential cluster model

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Chinese Physics C 2024年第4期48卷 130-145页

作者： s.B.Dubovichenko A.s.Tkachenko R.Ya.Kezerashvili N.A.Burkova B.M.Yeleusheva Fesenkov Astrophysical Institute 050020 AlmatyKazakhstan New York City College of Technology City University of New YorkBrooklyn11201 New YorkUSA Graduate school and University Center City University of New York10016 New YorkUSA al-Farabi Kazakh National University 050040 AlmatyKazakhstan

We study radiative p^(15)N capture on the ground state of ^(16)O at stellar energies within the framework of a modified potential cluster model(MPCM)with forbidden states,including low-lying *** investigation of the ^(15)N(p,γ0)^(16)O reaction includes the consideration of ^(3)s_(1) resonances due to E1 transitions and the contribution of the ^(3)P_(1) scattering wave in the p+^(15)N channel due to the ^(3)P_(1)→^(3)P_(0)M1 *** calculated the astrophysical low-energy s-factor,and the extrapolated s(0)turned out to be within 34.7−40.4 keV·*** important role of the asymptotic constant(AC)for the ^(15)N(p,γ0)16O process with interfering ^(3)s_(1)(312)and ^(3)s_(1)(962)resonances is elucidated.A comparison of our calculation for the s-factor with existing experimental and theoretical data is addressed,and a reasonable agreement is *** reaction rate is calculated and compared with the existing *** has negligible dependence on the variation of AC but shows a strong impact of the interference of ^(3)s_(1)(312)and ^(3)s_(1)(962)resonances in reference to the CNO Gamow windows,especially at low *** estimate the contribution of cascade transitions to the reaction rate based on the exclusive experimental data from ***.C.85,065810(2012).The reaction rate enhancement due to the cascade transitions is observed from T_(9)>0.3 and reaches the maximum factor~1.3 at T_(9)=*** present the Gamow energy window and a comparison of rates for radiative proton capture reactions ^(12)N(p,γ)^(13)O,^(13)N(p,γ)^(14)O,^(14)N(p,γ)^(15)O,and ^(15)N(p,γ)^(16)O obtained in the framework of the MPCM and provide the temperature windows,prevalence,and significance of each process.

关键词： low and astrophysical energies p^(15)N system thermonuclear reaction rate potential cluster model CNO-cycle