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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

The impact of alpha-fetoprotein(AFP),child-turcotte-pugh(CTP)score and disease staging on the survival of hepatocellular carcinoma(HCC)patients:a retrospective cohort from single oncology center

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Oncology Research 2025年第1期33卷 149-160页

作者： NASSER MULLA YOUSEF KATIB ASIM M.ALMUGHAMSI DUAA S.ALKHAYAT MOHAMED MOSAAD SAMIR T.ALFOTIH RAWAN ALAOFI Department of Internal medicine Faculty of MedicineTaibah UniversityMadinah42278Saudi Arabia Department of Radiology Faculty of MedicineTaibah UniversityMadinah42278Saudi Arabia Department of Surgery Faculty of MedicineTaibah UniversityMadinah42278Saudi Arabia Department of Endemic and Infectious Diseases Suez Canal UniversityIsmailia41522Egypt King Salman bin Abdulaziz Medical City Madinah42311Saudi Arabia Prince Mohammed Bin Abdulaziz Hospital Madinah41511Saudi Arabia

Background:Hepatocellular carcinoma(HCC)is the most common cause of cancer-related death in Saudi *** study aimed to investigate the patterns of HCC and the effect of TNM staging,Alfa-fetoprotein(AFP),and Child-Turcotte Pugh(CTP)on patients’overall survival(OS).Methods:A retrospective analysis was conducted on 43 HCC patients at a single oncology center in Saudi Arabia from 2015 to *** patients had to fulfill one of the following criteria:(a)a liver lesion reported as definitive HCC on dynamic imaging and/or(b)a biopsy-confirmed ***:The mean patient age of all HCC cases was 66.8 with a male-to-female ratio of 3.3:*** patients were stratified into two groups:viral HCC(n=22,51%)and non-viral HCC(n=21,49%).Among viral-HCC patients,55%were due to HBV and 45%due to *** was diagnosed in 79%of *** and sex did not significantly statistically differ in OS among viral and non-viral HCC patients(p-value>0.05).About 65%of patients had tumor size>5 cm during the diagnosis,with a significant statistical difference in OS(p-value=0.027).AFP was>400 ng/ml in 45%of the *** was a statistically significant difference in the OS in terms of AFP levels(p-value=0.021).A statistically significant difference was also observed between the CTP score and OS(p-value=0.02).CTP class B had the longest *** was the most common treatment provided to HCC patients followed by sorafenib *** was a significant statistical difference in OS among viral and non-viral HCC patients(p-value=0.008).Conclusions:The most common predictors for OS were the underlying cause of HCC,AFP,and tumor *** having non-viral etiology,a tumor size>5 cm,an AFP>400 ng/mL,and a CTP score class C were all negatively associated with OS.

关键词： Hepatocellular carcinoma Pattern Alpha-fetoprotein(AFP) Child-turcotte-pugh Progression free survival

Effect of gamification applications on success of dentistry students

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World Journal of Methodology 2025年第1期15卷 80-87页

作者： Hatice Ahsen Deniz Elif Polat Balkan Burak İncebeyaz Kıvanç Kamburoğlu Department of Dentomaxillofacial Radiology Ankara University Faculty of DentistryAnkara 06500Türkiye

BACKGROUND Gamification,the use of game materials in education,has been used in several scientific fields,and studies have demonstrated its effectiveness in student *** To evaluate whether the success of 4th-and 5th-grade dentistry students increases when using the gamification applications Kahoot!and *** An experimental design was used to measure the effect of gamification applications on students who were taught using the traditional *** this purpose,Mentimeter and Kahoot!applications were used in this experimental *** groups of 4th-and 5th-grade students were formed:Mentimeter,Kahoot!,and control *** effect of gamification applications on achievement was evaluated by administering a post-test to these groups after the instructional ***-way analysis of variance and t-tests were used for statistical *** A total of 35.5%of the students were in the Mentimeter group,29.8%in the Kahoot!group,and 34.6%in the control *** the total number of students,54.8%were female and 45.2%were male,while 52.2%were 5th-grade students and 47.8%were 4th-grade *** overall grade point average was found to be 66.65(range,24-100).There was a statistically significant difference in average success scores between students of different groups(P=0.003<0.05)and grades(P=0.036<0.05).The average success score was the highest in the Mentimeter group(71.64)and the lowest in the Kahoot!group(62.15).In the control group,this score was *** average success score was higher for students in the 5thgrade(68.16)and for female students(68.84).CONCLUSION Gamification has a great potential in the education of dentomaxillofacial radiology *** outperformed both the Kahoot!and the traditional method in terms of average student success rates.

关键词： Gamification Mentimeter Kahoot! Education Dentistry

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

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)

Fatigue Strength Analysis of Dissimilar Aluminum Alloy TIG Welds

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Journal of Wuhan university of Technology(Materials Science) 2025年第1期40卷 265-274页

作者： LIAO Xiangyun WANG Ruijie LIU Guoshou ZHAO Pinglin faculty of Mechanical and Electrical Engineering Kunming University of Science and TechnologyKunming 650500China faculty of Civil Engineering and Mechanics Kunming University of Science and TechnologyKunming 650500China

The constant amplitude loading fatigue tests were carried out on the 6061/7075 aluminum alloy TIG fillet welded lap specimens in this study,and the weld seam cross-section hardness was *** experimental results show that most specimens mainly failed at the 7075 side weld toes even though the base material tensile strength of 7075 is higher than that of *** maximum stress-strain concentration in the two finite element models is located at the 7075 side weld toe,which is basically consistent with the actual fracture *** weld zone on the 7075 side experiences severe material softening,with a large ***,the Vickers hardness value on the 6061 side negligibly changes and fluctuates around 70 *** obvious defects are found on the fatigue fracture,but a large number of secondary cracks *** germinate from the weld toe and propagate in the direction of the plate *** reinforcement has a serious impact on fatigue *** life will decrease exponentially as the weld reinforcement increases under low *** is found that the notch stress method can give a better fatigue life prediction for TIG weldments,and the errors of the predicted results are within the range of two factors,while the prediction accuracy decreases under low *** equivalent structural stress method can also be used for fatigue life prediction of TIG weldments,but the errors of prediction results are within the range of three factors,and the accuracy decreases under high stress.

关键词： TIG welding notch stress method equivalent structural stress method fatigue life finite element analysis