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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani Christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

Dynamic Multi-Graph Spatio-Temporal Graph Traffic Flow Prediction in Bangkok:An Application of a Continuous Convolutional Neural Network

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 579-607页

作者： Pongsakon Promsawat Weerapan Sae-dan Marisa Kaewsuwan Weerawat Sudsutad Aphirak Aphithana Department of Civil Engineering Faculty of EngineeringRamkhamkaeng UniversityBangkok10240Thailand Department of Computer Engineering Faculty of EngineeringRamkhamkaeng UniversityBangkok10240Thailand Department of Statistics Faculty of ScienceRamkhamkaeng UniversityBangkok10240Thailand

The ability to accurately predict urban traffic flows is crucial for optimising city ***,various methods for forecasting urban traffic have been developed,focusing on analysing historical data to understand complex mobility *** learning techniques,such as graph neural networks(GNNs),are popular for their ability to capture spatio-temporal ***,these models often become overly complex due to the large number of hyper-parameters *** this study,we introduce Dynamic Multi-Graph Spatial-Temporal Graph Neural Ordinary Differential Equation Networks(DMST-GNODE),a framework based on ordinary differential equations(ODEs)that autonomously discovers effective spatial-temporal graph neural network(STGNN)architectures for traffic prediction *** comparative analysis of DMST-GNODE and baseline models indicates that DMST-GNODE model demonstrates superior performance across multiple datasets,consistently achieving the lowest Root Mean Square Error(RMSE)and Mean Absolute Error(MAE)values,alongside the highest *** the BKK(Bangkok)dataset,it outperformed other models with an RMSE of 3.3165 and an accuracy of 0.9367 for a 20-min interval,maintaining this trend across 40 and 60 ***,on the PeMS08 dataset,DMST-GNODE achieved the best performance with an RMSE of 19.4863 and an accuracy of 0.9377 at 20 min,demonstrating its effectiveness over longer *** Los_Loop dataset results further emphasise this model’s advantage,with an RMSE of 3.3422 and an accuracy of 0.7643 at 20 min,consistently maintaining superiority across all time *** numerical highlights indicate that DMST-GNODE not only outperforms baseline models but also achieves higher accuracy and lower errors across different time intervals and datasets.

关键词： Graph neural networks convolutional neural network deep learning dynamic multi-graph spatio-temporal

Synergistic effect of bonding heterogeneity and phonon localization in introducing excellent thermoelectric properties in layered heteroanionic NdZnSbO material

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Journal of Energy Chemistry 2025年第1期100卷 259-272页

作者： Da Wan Shuwei Tang Shulin Bai Xiaodong Li Peng Ai Wanrong Guo Tuo Zheng College of Materials Science and Engineering Liaoning Technical University faculty of Chemistry Northeast Normal University

Layered rare-earth metal oxides, harnessing the dual properties of oxides and two-dimensional layered materials, exhibit remarkable thermal stability and quantum confinement effects. Therefore, this work adopts the first-principles calculation combined with the Boltzmann transport theory to predict the thermoelectric properties of NdZnSbO compound. The coexistence of weak interlayer van der Waals interactions, robust intralayer ionic bonding, and partial covalent bonding leads to remarkable bonding heterogeneity, which engenders pronounced phonon scattering and imposes constraints on thermal transport along the out-of-plane direction. The weakened chemical bonds induced by the antibonding states, together with the rattling-like behavior of the Zn atom, culminate in the profound anharmonicity in the layered NdZnSbO compound. The weakening bond and heavy element contribute to the softness of phonon modes, which significantly diminishes the phonon group velocity. The redistribution-dominated four-phonon scattering process spans a large optical gap, which effectively reduces the lattice thermal conductivity. The NdZnSbO compound exhibits direct semiconductor characteristic with a bandgap of 0.73 e V by adopting the Heyd-Scuseria-Ernzerhof(HSE06) functional in combination with spin–orbit coupling(SOC) effect. The multi-valley feature of NdZnSbO compound augur favorably for band degeneracy, thus amplifying the power factor. Consequently, an optimal figure-of-merit(ZT) of 3.40 at 900 K is achieved for the n-type NdZnSbO compound. The present study delves deeply insights into the origins for the low thermal conductivity of NdZnSbO compound and proposes an optimization scheme to enhance overall thermoelectric performance.

关键词： Bond strength (chemical)

Proteostasis failure:at the intersection between aging and Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3221-3222页

作者： Natalia Poblete Claudio Hetz Center for Geroscience Brain Health and MetabolismSantiagoChile Biomedical Neuroscience Institute Faculty of MedicineUniversity of ChileSantiagoChile Program of Cellular and Molecular Biology Institute of Biomedical SciencesFaculty of MedicineUniversity of ChileSantiagoChile Buck Institute for Research on Aging NovatoCAUSA

Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of *** we have gained important insights into the pathogenic mechanisms of AD,only palliative care is available to *** is characterized by the abnormal deposition of protein aggregates in the brain formed by amyloid β and hyper-phosphorylated,Tau in addition to neuroinflammation.

关键词： Alzheimer amyloid stasis

Genistein:a possible solution for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第10期20卷 2903-2905页

作者： Karolina Pierzynowska Bartosz Karaszewski Grzegorz Węgrzyn Department of Molecular Biology University of GdanskGdanskPoland Gdansk Polandand Department of Adult NeurologyFaculty of MedicineMedical University of GdanskGdanskPoland

Neurodegenerative diseases are defined as disorders resulting from the slow and progressive loss of function and eventual death of neural cells that result from the primary pathology of nervous *** can lead to severe nervous system dysfunction,eventually affecting multiple organs and *** hundred neurodegenerative diseases have been described,and owing to their prevalence,severity.

关键词： organs Alzheimer death

Understanding activity of butyrate at a cellular level

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Neural Regeneration Research 2025年第8期20卷 2323-2324页

作者： Prapti Chakraborty Angela S.Laird Macquarie university Motor Neuron Disease Research Centre Macquarie Medical SchoolFaculty of MedicineHealth and Human SciencesMacquarie UniversitySydneyAustralia

Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the *** the years,butyrate has attracted ... 详细信息

关键词： carbons butyrate fiber

Acquired sensorineural hearing loss,oxidative stress,and microRNAs

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Neural Regeneration Research 2025年第9期20卷 2513-2519页

作者： Desmond A.Nunez Ru C.Guo Division of Otolaryngology–Head&Neck Surgery Department of SurgeryFaculty of MedicineThe University of British ColumbiaVancouverBCCanada Division of Otolaryngology–Head&Neck Surgery Gordon&Leslie Diamond Health Care CentreVancouver General HospitalVancouverBCCanada faculty of medicine–The university of British Columbia VancouverBCCanada

Hearing loss is the third leading cause of human ***-related hearing loss,one type of acquired sensorineural hearing loss,is largely responsible for this escalating global health ***-induced,ototoxic,and idiopathic sudden sensorineural are other less common types of acquired hearing *** etiology of these conditions is complex and multi-fa ctorial involving an interplay of genetic and environmental *** stress has recently been proposed as a likely linking cause in most types of acquired sensorineural hearing *** non-coding RNA sequences known as microRNAs(miRNAs)have increasingly been shown to play a role in cellular hypoxia and oxidative stress responses including promoting an apoptotic *** hair cell death is a central histopathological finding in sensorineural hearing *** these cells do not regenerate in humans,it underlies the irreversibility of human age-related hearing *** EMBASE,Ovid MEDLINE,Web of Science Core Collection,and *** databases over the period August 1,2018 to July 31,2023 were searched with"hearing loss,""hypoxamiRs,""hypoxia,""microRNAs,""ischemia,"and"oxidative stress"text words for English language primary study publications or registered clinical *** red clinical trials known to the senior author we re also assessed.A total of 222studies were thus *** excluding duplicates,editorials,retra ctions,secondary research studies,and non-English language articles,39 primary studies and clinical trials underwent full-text *** resulted in 11 animal,in vitro,and/or human subject journal articles and 8 registered clinical trial database entries which form the basis of this narrative *** miR-34a and miR-29b levels increase with age in *** miRNAs were demonstrated in human neuroblastoma and murine cochlear cell lines to target Sirtuin 1/peroxisome proliferato r-activated receptor gamma coactivator-1-alpha(SIRT1/P GC-1α),SIRT

关键词： hearing loss hypoxia microRNAs oxidative stress sensorineural

Potential of non-Western medicines in chemoradiotherapy for cervical cancer

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World Journal of Clinical Cases 2025年第2期13卷 21-23页

作者： Takashi Ono Masashi Koto Department of Radiation Oncology Faculty of MedicineYamagata UniversityYamagata 990-9585Japan

This editorial explores the potential integration of non-Western medicine into radiotherapy for cervical *** radiotherapy remains a radical treatment for cervical cancer,its associated toxicity and decline in quality of life can significantly impact patients’***,most treatments are supportive,with no specific treatment options available in Western ***-Western medicine,often less toxic and easier to administer,has shown promising results when used alongside radiotherapy for cervical *** these potential benefits,challenges such as limited evidence and restricted application areas *** non-Western medicines may offer potential improvements in chemoradiotherapy outcomes for cervical cancer,further research is necessary to substantiate these benefits.

关键词： Cervical cancer Radiotherapy Non-Western medicine Kampo Herbal medicine

Dynamic stress concentration in an infinitely long cylindrical cavity due to a point spherical source embedded within a fluid-saturated poroelastic formation of infinite extent

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 139-156页

作者： H.HOSSEINI O.BALILASHAKI Department of Mechanical Engineering Faculty of EngineeringGolestan University

The effects of a harmonically exciting monopole source on an infinitely long cylindrical cavity embedded entirely within a fluid-saturated poroelastic formation of infinite extent are examined theoretically. It is assumed that the source is located outside the cavity at a specified distance from the borehole axis. The magnitudes of the hoop and radial stresses beside the pore pressures exerted on the interface and inside the porous medium surrounding the borehole are calculated and discussed. Biot's poroelastic modeling along with three types of boundary conditions for the cylindrical interface including the ideal fluid, empty borehole, and rigid inclusion with a hard boundary is employed for the analysis. Utilizing a proper translational addition theorem for expressing the incident spherical wave in terms of cylindrical wave expansions, the proposed boundary conditions at the interface are satisfied. Stresses are formulated by means of wave potential functions in a three-dimensional(3D) manner. The effects of the frequency and the radial distance between the source and borehole on the induced stresses are examined for the first cylindrical modes over frequency spectra. Two permeability conditions for the interface and three types of soils for the porous formation are considered throughout the analysis. To give an overall outline of the study, a numerical example is presented. The results clearly indicate that the distance is a key parameter and has considerable effects on the induced stress values. In addition, the interface permeability condition and soil characteristics play an important role in determining the dynamic response of the borehole. Finally,the obtained results are compared with the relevant analyses existing in the literature for some limit cases, and good agreement is achieved.

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