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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

Three-dimensional models:from cell culture to Patient-Derived Organoid and its application to future liposarcoma research

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Oncology Research 2025年第1期33卷 1-13页

作者： SAYUMI TAHARA SYDNEY RENTSCH FERNANDA COSTAS CASAL DE FARIA PATRICIA SARCHET ROMA KARNA FEDERICA CALORE RAPHAEL E.POLLOCK Department of Surgery Division of Surgical OncologyThe James Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusOH 43210USA Department of Cancer Biology and genetics The James Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusOH 43210USA

Liposarcoma is one of the most common soft tissue sarcomas,however,its occurrence rate is still rare compared to other *** to its rarity,in vitro experiments are an essential approach to elucidate liposarcoma *** cell culture-based research(2D cell culture)is still playing a pivotal role,while several shortcomings have been recently under *** vivo,mouse models are usually adopted for pre-clinical analyses with expectations to overcome the issues of 2D cell ***,they do not fully recapitulate human dedifferentiated liposarcoma(DDLPS)***,three-dimensional(3D)culture systems have been the recent research focus in the cell biology field with the expectation to overcome at the same time the disadvantages of 2D cell culture and in vivo animal models and fill in the gap between *** the liposarcoma rarity,we believe that 3D cell culture techniques,including 3D cell cultures/co-cultures,and Patient-Derived tumor Organoids(PDOs),represent a promising approach to facilitate liposarcoma investigation and elucidate its molecular mechanisms and effective therapy *** this review,we first provide a general overview of 3D cell cultures compared to 2D cell *** then focus on one of the recent 3D cell culture applications,Patient-Derived Organoids(PDOs),summarizing and discussing several PDO ***,we discuss the current and future applications of PDOs to sarcoma,particularly in the field of liposarcoma.

关键词： Cell culture Liposarcoma Patient-Derived Organoid(PDO) Spheroid Three-dimensional(3D)cell culture

ImSpiRE: image feature-aided spatial resolution enhancement method

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Science China Life Sciences 2025年第1期68卷 272-283页

作者： Yuwei Hua Yizhi Zhang Zhenming Guo Shan Bian Yong Zhang State Key Laboratory of cardiovascular Diseases and Medical Innovation center Institute for Regenerative MedicineDepartment of NeurosurgeryShanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji University

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with extending the gene expression profiles into unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

关键词： spatial transcriptome histological images spatial resolution enhancement

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

Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon Choi genetics and Aging Research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance center for Brain Health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第9期20卷 2556-2570页

作者： Yongting Lv Hongfu Li Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Medical genetics and center for Rare disease Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Nanhu Brain-Computer Interface Institute HangzhouZhejiang Province

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely *** principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial *** biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even *** these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and *** light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and ***,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal *** fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration *** DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related *** is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease *** the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable *** review summarizes the lat

关键词： amyotrophic lateral sclerosis biomarker blood biomarkers diagnosis glial fibrillary acidic protein neurofilament light chain prognosis TAR DNA-binding protein 43

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Evaluating the impacts of converting grain to vegetable fields on nitrate transport in the deep vadose zone of the North China Plain

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Journal of Geographical Sciences 2025年第1期35卷 189-212页

作者： LIU Meiying MIN Leilei WU Lin ZHANG Yucui QI Yongqing WANG Shiqin LIU Binbin GENG Di SHEN Yanjun Hebei Key Laboratory of Water-Saving Agriculture Key Laboratory of Agricultural Water ResourcesCenter for Agricultural Resources ResearchInstitute of Genetics and Developmental BiologyCAS School of Advanced Agricultural Sciences University of Chinese Academy of Sciences

Nitrate （NO3-） accumulation and transport processes in the thick vadose zone affect the evolution of the groundwater NO3-content in intensive agricultural *** land-use change （ALUC）,typically accompanied by substantial alterations in nitrogen fertilizer application and irrigation practices,is an important influencing *** study evaluated the changes in NO3-accumulation and transport in the deep vadose zone （DVZ,below the root zone）,and the groundwater NO3-content associated with ALUC from grain to vegetable fields in the North China Plain （NCP）.The ALUC from grain to vegetable resulted in nitrate–nitrogen （NO3--N） accumulation in DVZ increased by 235.5 kg ha-1m-1（163.2%） in the piedmont plain and 224.9 kg ha-1m-1（102.7%） in the central plain,*** change accelerated downward transport velocity in the DVZ (from 0.81±0.47 to 0.89±0.55 m yr-1in the piedmont plain,and from 0.24±0.12 to 0.92±0.12 m yr-1in the central plain) and increased NO3-leaching *** transport velocity and leaching fluxes resulted in chemical N-fertilizer entering the aquifer in several areas in the piedmont *** impact of the agricultural activity intensity changes,accompanied by the ALUC,on groundwater quantity and quality should be considered in similar regions.

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Rational design of lipid-activatable NIR-II probes for precisely imaging atherosclerotic plaque

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Science China Chemistry 2025年

作者： Xinyu Xu Yuan Ma Hui Cao Li Xu Haoming Chen Sulai Liu Wei Sun Guosheng Song Xiaobing Zhang State Key Laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical EngineeringHunan University Department of Hepatobiliary Surgery/Central Laboratory Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) Department of Cardiology the First Affiliated Hospital of Nanjing Medical University Key Laboratory of Targeted Intervention of cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical University Shenzhen Research Institute of Hunan University

Atherosclerosis(AS) is a prevalent condition associated with cardiovascular and cerebrovascular diseases, featuring lipid-laden plaque; however, the insufficient resolution and low sensitivity of traditional medical imaging techniques limit their application in lipid imaging. Currently, the second near-infrared(NIR-II) fluorescence imaging offers promising sensitivity and convenience. However, existing probes have limitations in terms of signal-to-background ratio, penetration depth, and tissue scattering. Herein, we use a molecular regulatory strategy to design a lipid-activatable probe Rh-965 with high specificity and NIR-II emission for improved imaging potential in deep tissues. The potential of Rh-965 for imaging plaque lipids in mice with AS is demonstrated by localizing carotid artery plaques using NIR-II imaging. The development of more stable lipid-activated NIR-II probes can significantly enhance atherosclerosis diagnosis and facilitate in vivo imaging in deeper tissues.

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