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Interplay between the glymphatic system and neurotoxic proteins in Parkinson’s disease and related disorders:current knowledge and future directions

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Neural Regeneration research 2024年第9期19卷 1973-1980页

作者： Yumei Yue Xiaodan Zhang Wen Lv Hsin-Yi Lai Ting Shen Department of Neurology of Sir Run Run Shaw Hospital Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Emergency Medicine The University of Hong KongHong Kong Special Administrative RegionChina Department of Neurology of the Second Affiliated Hospital and School of Brain science and Brain Medicine Interdisciplinary Institute of Neuroscience and TechnologyKey Laboratory of Medical Neurobiology of Zhejiang ProvinceZhejiang University School of MedicineHangzhouZhejiang ProvinceChina College of Biomedical Engineering and Instrument science Zhejiang UniversityHangzhouZhejiang ProvinceChina MOE Frontier science Center for Brain science and Brain-Machine Integration State Key Laboratory of Brain-machine IntelligenceSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina

Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.

关键词： atypical parkinsonism glymphatic system magnetic resonance imaging neurotoxic proteins Parkinson’s disease

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Utility of real-time 3D visualization system in the early stage of phacoemulsification training

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 577-582页

作者： Zhe Xu Dan Chen Jing-Wei Xu Yi-Xuan Feng Ce Shi Li Zhang Wen Xu Eye Center the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009Zhejiang ProvinceChina zhejiang Provincial Key Laboratory of Ophthalmology Hangzhou 310009Zhejiang ProvinceChina zhejiang Provincial Clinical research Center for Eye Diseases Hangzhou 310009Zhejiang ProvinceChina zhejiang Provincial Engineering institute on Eye Diseases Hangzhou 310009Zhejiang ProvinceChina

●AIM:To determine the teaching effects of a real-time three dimensional(3D)visualization system in the operating room for early-stage phacoemulsification training.●METHODS:A total of 10 ophthalmology residents of the first-year postgraduate were included.All the residents were novices to cataract surgery.Real-time cataract surgical observations were performed using a custom-built 3D visualization system.The training lasted 4wk(32h)in all.A modified International Council of Ophthalmology’s Ophthalmology Surgical Competency Assessment Rubric(ICO-OSCAR)containing 4 specific steps of cataract surgery was applied.The self-assessment(self)and expert-assessment(expert)were performed through the microsurgical attempts in the wet lab for each participant.●RESULTS:Compared with pre-training assessments(self 3.2±0.8,expert 2.5±0.6),the overall mean scores of posttraining(self 5.2±0.4,expert 4.7±0.6)were significantly improved after real-time observation training of 3D visualization system(P<0.05).Scores of 4 surgical items were significantly improved both self and expert assessment after training(P<0.05).●CONCLUSION:The 3D observation training provides novice ophthalmic residents with a better understanding of intraocular microsurgical techniques.It is a useful tool to improve teaching efficiency of surgical education.

关键词： 3D visualization system phacoemulsification training wet lab

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Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3β Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第7期30卷 588-599页

作者： JIANG Yu-xia ZHAO Yan-na YU Xiao-ling YIN Li-ming Department of Hematology Tongde Hospital of Zhejiang Province institute of Hematology research the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)

Objective: To investigate the role of ginsenoside Rd（GRd） in acute myeloid leukemia（AML） cell differentiation. Methods: AML cells were treated with GRd（25, 50, 100 and 200 μg/mL）, retinoic acid（RA, 0.1g/L） and PD98059（20 mg/mL） for 72 h, cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays, and cell cycle was detected by flow cytometry. Cell morphology and differentiation were observed by Wright-Giemsa staining, peroxidase chemical staining and cellular immunochemistry assay, respectively. The protein expression levels of GATA binding protein 1（GATA-1）, purine rich Box-1（PU.1）, phosphorylated-extracellular signal-related kinase（p-ERK）, ERK, phosphorylated-glycogen synthase kinase-3β（p-GSK3β）, GSK3β and signal transducer and activator of transcription 1（STAT1） were detected by Western blot. Thirty-six mice were randomly divided into 3 groups using a random number table: model control group（non-treated）, GRd group [treated with 200 mg/（kg·d） GRd] and homoharringtonine（HTT） group [treated with 1 mg/（kg·d） HTT]. A tumor-bearing nude mouse model was established, and tumor weight and volume were recorded. Changes of subcutaneous tumor tissue were observed after hematoxylin and eosin staining. WT1 and GATA-1 expressions were detected by immunohistochemical staining. Results: The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1cell arrest（P<0.05）. GRd treatment induced leukemia cell differentiation, showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation（P<0.05）. GRd treatment elicited upregulation of p-ERK, p-GSK-3β and STAT1 expressions in cells, and reversed the effects of PD98059 on inhibiting the expressions of peroxidase, GATA-1 and PU.1（P<0.05）. After GRd treatment, tumor weight and volume of mice were decreased, and tumor cells underwent massive apoptosis and necrosis（P<0.05）. WT1 level was decreased, and GATA-1 level was significantly increased in subcutaneous tumor

关键词： ginsenoside Rd myeloid leukemia survival differentiation extracellular signal-related kinase signaling pathway

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Influencing Factors of Healthy Aging Risk Assessed Using Biomarkers:A Life Course Perspective

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China CDC weekly 2024年第11期6卷 219-224,I0014-I0017页

作者： Cedric Zhang Bo Lua Yajie Gao Jinming Li Xingqi Cao Xinwei Lyu Yinuo Tu Shuyi Jin Zuyun Liu Center for Clinical Big Data and Analytics of the Second Affiliated Hospital and Department of Big Data in Health Science School of Public Healththe Key Laboratory of Intelligent Preventive Medicine of Zhejiang ProvinceZhejiang University School of MedicineHangzhou CityZhejiang ProvinceChina institute of Epidemiology and Health Care University College LondonLondonUK College of Chemical and Biological Engineering Zhejiang UniversityHangzhou CityZhejiang ProvinceChina

Assessing individual risks of healthy aging using biomarkers and identifying associated factors have become important areas of research.In this study,we conducted a literature review of relevant publications between 2018 and 2023 in both Chinese and English databases.Previous studies have predominantly used single biomarkers,such as C-reactive protein,or focused on specific life course stages and factors such as socioeconomic status,mental health,educational levels,and unhealthy lifestyles.By summarizing the progress in this field,our study provides valuable insights and future directions for promoting healthy aging from a life course perspective.

关键词： such insight directions

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PDGFR in PDGF-BB/PDGFR Signaling Pathway Does Orchestrates Osteogenesis ina Temporal Manner

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research 2024年第1期2023卷 33-48页

作者： Fangqian Wang Yuxiao Ye Zengjie Zhang Wangsiyuan Teng Hangxiang Sun Xupeng Chai Xingzhi Zhou Jiayu Chen Haochen Mou Yinwang Eloy Xiaoqiang Jin Liang Chen Zhenxuan Shao Yan Wu Yue Shen An Liu Peng Lin Jianwei Wang Xiaohua Yu Zhaoming Ye Department of Orthopedic Surgery the Second Affiliated HospitalZhejang University School of MedicineHangzhou CityZhejiang ProvincePR China Orthopedics research institute of Zhejang University Hangzhou CityZhejiang ProvincePR China Key Laboratory of Motor System Disease research and Precision Therapy of zhejiang province Hangzhou CityZhejiang ProvincePR China School of Material science and Engineering University of New South WalesSydney 2052Australia

Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.

关键词： healing sized implantation

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A feedback control method for phase signal demodulation in fber-optic hydrophones

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Applied Mathematics and Mechanics(English Edition) 2024年第3期45卷 515-528页

作者： Zhiqiang LIU Lei XIA Qiangfeng LYU Bin WU Ronghua HUAN Zhilong HUANG Department of Mechanics Key Laboratory of Soft Machines and Smart Devices of Zhejiang ProvinceZhejiang UniversityHangzhou 310000China Huanjiang Laboratory Zhuji 311899Zhejiang ProvinceChina Advanced Technology research institute Zhejiang UniversityHangzhou 310000China

In the realm of acoustic signal detection,the identification of weak signals,particularly in the presence of negative signal-to-noise ratios,poses a significant challenge.This challenge is further heightened when signals are acquired through fiber-optic hydrophones,as these signals often lack physical significance and resist clear systematic modeling.Conventional processing methods,e.g.,low-pass filter(LPF),require a thorough understanding of the effective signal bandwidth for noise reduction,and may introduce undesirable time lags.This paper introduces an innovative feedback control method with dual Kalman filters for the demodulation of phase signals with noises in fiber-optic hydrophones.A mathematical model of the closed-loop system is established to guide the design of the feedback control,aiming to achieve a balance with the input phase signal.The dual Kalman filters are instrumental in mitigating the effects of signal noise,observation noise,and control execution noise,thereby enabling precise estimation for the input phase signals.The effectiveness of this feedback control method is demonstrated through examples,showcasing the restoration of low-noise signals,negative signal-to-noise ratio signals,and multi-frequency signals.This research contributes to the technical advancement of high-performance devices,including fiber-optic hydrophones and phase-locked amplifiers.

关键词： feedback control method fiber-optic hydrophone acoustic signal detection phase signal

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Response of ocean acidification to atmospheric carbon dioxide removal

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Journal of environmental sciences 2024年第6期140卷 79-90页

作者： Jiu Jiang Long Cao Xiaoyu Jin Zechen Yu Han Zhang Jianjie Fu Guibin Jiang School of Environment Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China State Key Laboratory of environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Key Laboratory of Geoscience Big Data and Deep Resources of zhejiang province School of Earth SciencesZhejiang UniversityHangzhou 310058China zhejiang Climate Center Hangzhou 310052China

Artificial CO_(2)removal from the atmosphere(also referred to as negative CO_(2)emissions)has been proposed as a potential means to counteract anthropogenic climate change.Here we use an Earth system model to examine the response of ocean acidification to idealized atmospheric CO_(2)removal scenarios.In our simulations,atmospheric CO_(2)is assumed to increase at a rate of 1%per year to four times its pre-industrial value and then decreases to the pre-industrial level at a rate of 0.5%,1%,2%per year,respectively.Our results show that the annual mean state of surface ocean carbonate chemistry fields including hydrogen ion concentration([H^(+)]),pH and aragonite saturation state respond quickly to removal of atmospheric CO_(2).However,the change of seasonal cycle in carbonate chemistry lags behind the decline in atmospheric CO_(2).When CO_(2)returns to the pre-industrial level,over some parts of the ocean,relative to the pre-industrial state,the seasonal amplitude of carbonate chemistry fields is substantially larger.Simulation results also show that changes in deep ocean carbonate chemistry substantially lag behind atmospheric CO_(2)change.When CO_(2)returns to its pre-industrial value,the whole-ocean acidity measured by[H^(+)]is 15%-18%larger than the pre-industrial level,depending on the rate of CO_(2)decrease.Our study demonstrates that even if atmospheric CO_(2)can be lowered in the future as a result of net negative CO_(2)emissions,the recovery of some aspects of ocean acidification would take decades to centuries,which would have important implications for the resilience of marine ecosystems.

关键词： Carbon dioxide removal Net negative CO_(2)emission Ocean acidification Climate change Earth system modeling

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Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

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Neural Regeneration research 2024年第10期19卷 2132-2143页

作者： Chengfu Zhang Mengsheng Qiu Hui Fu Center for Cognition and Brain Disorders The Affiliated Hospital of Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Psychiatry National Clinical Research Center for Mental Disordersand National Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina institute of Life sciences Key Laboratory of Organ Development and Regeneration of Zhejiang ProvinceCollege of Life and Environment SciencesHangzhou Normal UniversityHangzhouZhejiang ProvinceChina Key Laboratory of Aging and Cancer Biology of zhejiang province School of Basic Medical SciencesHangzhou Normal UniversityHangzhouZhejiang ProvinceChina

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

关键词： astrocyte central nervous system disease CXC chemokine cytokine interferonγ interleukin microglia oligodendrocyte oligodendrocyte precursor cell tumor necrosis factorα

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Tuning mechanical behaviors of highly entangled hydrogels with the random distribution of mobile entanglements

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Applied Mathematics and Mechanics(English Edition) 2024年第2期45卷 277-294页

作者： Jinlong LIU Di LU Bin CHEN Department of Engineering Mechanics Zhejiang UniversityHangzhou 310027China Beijing System design institute of Electro-Mechanic Engineering Beijing 100854China Intelligent Robotic research Center Zhejiang LaboratoryHangzhou 310027China Key Laboratory of Soft Machines and Smart Devices of zhejiang province Hangzhou 311100China

Highly entangled hydrogels exhibit excellent mechanical properties,including high toughness,high stretchability,and low hysteresis.By considering the evolution of randomly distributed entanglements within the polymer network upon mechanical stretches,we develop a constitutive theory to describe the large stretch behaviors of these hydrogels.In the theory,we utilize a representative volume element(RVE)in the shape of a cube,within which there exists an averaged chain segment along each edge and a mobile entanglement at each corner.By employing an explicit method,we decouple the elasticity of the hydrogels from the sliding motion of their entanglements,and derive the stress-stretch relations for these hydrogels.The present theoretical analysis is in agreement with experiment,and highlights the significant influence of the entanglement distribution within the hydrogels on their elasticity.We also implement the present developed constitutive theory into a commercial finite element software,and the subsequent simulations demonstrate that the exact distribution of entanglements strongly affects the mechanical behaviors of the structures of these hydrogels.Overall,the present theory provides valuable insights into the deformation mechanism of highly entangled hydrogels,and can aid in the design of these hydrogels with enhanced performance.

关键词： highly entangled hydrogel constitutive theory entanglement gamma distribution

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Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

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World Journal of Hepatology 2024年第4期16卷 601-611页

作者： Shuai-Jun Ren Jia-Ting Feng Ting Xiang Cai-Lian Liao Yu-Ping Zhou Rong-Rong Xuan Department of Obstetrics and Gynecology The First Affiliated Hospital of Ningbo UniversityNingbo 315100Zhejiang ProvinceChina Health science Center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Ningbo UniversityNingbo 315211Zhejiang ProvinceChina institute of Digestive Disease Ningbo UniversityNingbo 315020Zhejiang ProvinceChina

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.

关键词： Intrahepatic cholestasis of pregnancy Short-chain fatty acids Maternal serum Cord blood Caproic acid

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