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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

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Silk damping in scalar-induced gravitational waves: a novel probe for new physics

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 79-85页

作者： yan-Heng Yu Sai Wang Theoretical Physics Division Institute of High Energy Physics Chinese Academy of Sciences School of Physics University of Chinese Academy of Sciences

Silk damping is well known in the study of cosmic microwave background（CMB） and accounts for suppression of the angular power spectrum of CMB on large angular multipoles. in this article, we study the effect of Silk damping on the scalar-induced gravitational waves（SiGWs）. resulting from the dissipation of cosmic fluid, the Silk damping notably suppresses the energydensity spectrum of SiGWs on scales comparable to a diffusion scale at the decoupling time of weakly-interacting particles. The effect offers a novel observable for probing the underlying particle interaction, especially for those mediated by heavy gauge bosons beyond the standard model of particles. We anticipate that pulsar timing arrays are sensitive to gauge bosons with mass ～10～3-10～4 GeV, while space-and ground-based interferometers to those with mass ～10～7-1012GeV, leading to essential complements to on-going and future experiments of high-energy physics.

关键词： scalar-induced gravitational waves Silk damping new physics

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Neural regeneration research 2025年第2期20卷 366-377页

作者： Samuel Abokyi Dennis yan-yin Tse School of Optometry The Hong Kong Polytechnic UniversityKowloonHong Kong Special Administrative RegionChina research Center for SHArP Vision The Hong Kong Polytechnic UniversityKowloonHong Kong Special Administrative RegionChina Center for Eye and Vision research Sha TinHong Kong Special Administrative RegionChina

retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their *** comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor *** meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal *** review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal *** impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing *** vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal ***,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and *** retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in *** cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering pro

关键词： age-related macular degeneration anti-aging interventions autophagy calorie restriction diabetic retinopathy exercise glaucoma neuromodulation phagocytosis photoreceptor outer segment degradation retinal aging transcription factor EB

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The renaissance of oxo synthesis: heterogeneous rh-catalyzed hydroformylation

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Science China Chemistry 2025年

作者： Tao yan Zhi Cao State key Laboratory of Coal Conversion Institute of Coal Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences National Energy Center for Coal to Clean Fuels Synfuels China Technology Co. Ltd.

Hydroformylation could convert olefins and syngas （mixture of H2and CO） into aldehydes with a great atomic *** transformation serves as one of the most prominent processes in modern chemical industry, as it provides over 10million tons of aldehydes as feedstock for our daily essential products such as plasticizers, paints, solvents, and pharmaceuticals. This process generally requires efficient yet robust catalyst to realize decent efficacy. Compared with metals such as Co, ru, and Pd, rhodium （rh）-based catalysts stand out due to its superior activity even under mild reaction conditions, and dominate over 70%of global hydroformylation processes.

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revealing and predicting the long-term biomechanical response of orthokeratology by developing a patient-specific computational model

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 156-168页

作者： Yifeng Li Zhuoran yang Ziming yan Huibin Shi Zhanli Liu kaijie Wang Department of Engineering Mechanics School of Aerospace Engineering Tsinghua University Beijing Tongren Eye Center Beijing Tongren Hospital Capital Medical University Beijing Ophthalmology & Visual Sciences Key Lab

Orthokeratology(Ok) is widely used for effective myopia correction and control. However, the incomplete understanding of its biomechanical mechanisms makes Ok lens fitting rely heavily on clinician judgment, complicating accurate predictions of treatment outcomes. in this paper, we performed clinical experiments and numerical analysis to study corneal deformation modes and long-term changes in central corneal thickness. Clinical experiments were conducted on 194 Chinese myopic patients under Ok treatment for 3 months. Based on the experimental data, a patient-specific computational biomechanical model for Ok was established and validated. Specifically, the anisotropic mechanical properties of the cornea were incorporated into the model to describe the significant difference between its shear modulus(29.5 kPa) and tensile modulus(768.4 kPa). Additionally, a viscohyperelastic material model with a prolonged corneal relaxation time of 5.6 h was developed to capture the long-term deformation response. The results show that corneal thickness reduction in Ok is primarily due to out-of-plane shear deformation,influenced by the cornea's low shear resistance. Modeling the extended corneal relaxation time is crucial for predicting long-term biomechanical responses. The computational model effectively captures long-term changes in central corneal thickness, potentially improving Ok lens fitting accuracy.

关键词： orthokeratology computational biomechanical model long-term viscoelasticity myopia correction

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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

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Neural regeneration research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu Zhang yanyu Zhang yan Zeng Xingxing Chen Brain Science and Advanced Technology institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

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GFrF r-CNN:Object Detection Algorithm for Transmission Lines

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Computers, Materials & Continua 2025年第1期82卷 1439-1458页

作者： Xunguang yan Wenrui Wang Fanglin Lu Hongyong Fan Bo Wu Jianfeng Yu Shanghai Advanced research institute Chinese Academy of SciencesShanghai201210China University of Chinese Academy of Sciences Beijing100049China Jingwei Textile Machinery Co. Ltd.Beijing100176China

To maintain the reliability of power systems,routine inspections using drones equipped with advanced object detection algorithms are essential for preempting power-related *** increasing resolution of drone-captured images has posed a challenge for traditional target detection methods,especially in identifying small objects in high-resolution *** study presents an enhanced object detection algorithm based on the Faster regionbased Convolutional Neural Network(Faster r-CNN)framework,specifically tailored for detecting small-scale electrical components like insulators,shock hammers,and screws in transmission *** algorithm features an improved backbone network for Faster r-CNN,which significantly boosts the feature extraction network’s ability to detect fine *** region Proposal Network is optimized using a method of guided feature refinement(GFr),which achieves a balance between accuracy and *** incorporation of Generalized intersection over Union(GiOU)and region of interest(rOi)Align further refines themodel’s *** results demonstrate a notable improvement in mean Average Precision,reaching 89.3%,an 11.1%increase compared to the standard Faster *** highlights the effectiveness of the proposed algorithm in identifying electrical components in high-resolution aerial images.

关键词： Faster r-CNN transmission line object detection GiOU GFr

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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural regeneration research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza i.Torrado-Tapias iris k.Salgado Jose M.Santiago Samuel E.Ocasio rivera Dina P.Bracho-rincon Luis H.Pagan rivera Jorge D.Miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto rico Carolina CampusCarolinaPRUSA institute of Neurobiology San JuanPRUSA

in addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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Stability of triple diffusive convection in a viscoelastic fluid-saturated porous layer

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Applied Mathematics and Mechanics(English Edition) 2018年第10期39卷 1385-1410页

作者： k.r.rAGHUNATHA i.S.SHiVAkUMArA Department of Mathematics Bangalore University

The triple diffusive convection in an Oldroyd-B fluid-saturated porous layer is investigated by performing linear and weakly nonlinear stability analyses. The condition for the onset of stationary and oscillatory is derived analytically. Contrary to the observed phenomenon in Newtonian fluids, the presence of viscoelasticity of the fluid is to degenerate the quasiperiodic bifurcation from the steady quiescent state. Under certain conditions, it is found that disconnected closed convex oscillatory neutral curves occur, indicating the requirement of three critical values of the thermal Darcy-rayleigh number to identify the linear instability criteria instead of the usual single value, which is a novel result enunciated from the present study for an Oldroyd-B fluid saturating a porous medium. The similarities and differences of linear instability characteristics of Oldroyd-B, Maxwell, and Newtonian fluids are also highlighted. The stability of oscillatory finite amplitude convection is discussed by deriving a cubic Landau equation,and the convective heat and mass transfer are analyzed for different values of physical parameters.

关键词： Oldroyd-B fluid bifurcation instability perturbation method nonlinear stability heat and mass transfer

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Semantic rule Based image Visual Feature Ontology Creation

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international Journal of Automation and computing 2014年第5期11卷 489-499页

作者： r. i. Minu k. k. Thyagharajan Department of Computer Science & Engineering Jerusalem College of Engineering rMD Engineering College

Multimedia is one of the important communication channels for mankind. Due to the advancement in technology and enormous growth of mankind, a vast array of multimedia data is available today. This has resulted in the obvious need for some techniques for retrieving these data. This paper will give an overview of ontology-based image retrieval system for asteroideae flower family domain. in order to reduce the semantic gap between the low-level visual features of an image and the high-level domain knowledge, we have incorporated a concept of multi-modal image ontology. So, the created asteroideae flower domain specific ontology would have the knowledge about the domain and the visual features. The visual features used to define the ontology are prevalent color,basic intrinsic pattern and contour gradient. in prevalent color extraction, the most dominant color from the images was identified and indexed. in order to determine the texture pattern for a particular flower, basic intrinsic patterns were used. The contour gradients provide the information on the image edges with respect to the image base. These feature values are embedded in the ontology at appropriate slots with respect to the domain knowledge. This paper also defines some of the query axioms which are used to retrieve appropriate information from the created ontology. This ontology can be used for image retrieval system in semantic web.

关键词： information and knowledge computer vision intelligent computing feature extraction ontology

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