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Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease

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Neural Regeneration Research 2024年第8期19卷 1759-1767页

作者： Zihang Zhou Yalong yan Heng gu Ruiao Sun Zihan Liao Ke Xue Chuanxi Tang Department of Neurobiology Xuzhou Key Laboratory of NeurobiologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive impairment.One common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive functioning.Executive functions help us plan,organize,and control our actions based on our goals.The brain area responsible for executive functions is called the prefrontal co rtex.It acts as the command center for the brain,especially when it comes to regulating executive functions.The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine.However,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s disease.In this article,the authors review the latest research on this topic.They start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive dysfunction.Then,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal cortex.The authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive issues.This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.

关键词： dopamine dopamine receptor dopamine transporter executive dysfunction neural network neural oscillation prefrontal cortex synaptic plasticity

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Influence of transcatheter arterial embolization on symptom distress and fatigue in liver cancer patients

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 810-818页

作者： Xu-Min yang Xu-yan yang Xin-Yu Wang Yue-Xia gu Department of Nursing The First Affiliated Hospital of Naval Medical University(Changhai Hospital)Shanghai 200433China Department of Thyroid Breast and Vascular SurgeryShanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China Department of Nursing Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China

BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignancy,and transcatheter arterial embolization(TAE)has emerged as a pivotal therapeutic modality.How-ever,TAE may induce symptom distress and fatigue,adversely affecting the quality of life of patients.AIM To investigate symptom distress,fatigue,and associated factors in HCC patients undergoing TAE.METHODS We used a cross-sectional design and purposive sampling to enroll HCC patients who underwent TAE at our institution from January to December 2022.Question-naires were utilized to collect data on symptom distress and fatigue scores from the first to the third day after TAE.RESULTS Our study revealed a significant reduction in fatigue and symptom distress among patients after TAE.Pain,fatigue,insomnia,fever and abdominal dis-tension were the most common symptoms troubling patients during the first 3 d post-TAE.Marital status,presence of family support,physical functional status,age,and symptom distress were identified as predictors of fatigue in patients.CONCLUSION Healthcare professionals should educate HCC patients on symptom distress and INTRODUCTION Hepatocellular carcinoma(HCC)ranks as the fifth most prevalent cancer and the third leading cause of cancer-related mortality globally.Surgical intervention remains the cornerstone of HCC treatment;however,due to the challenges associated with early diagnosis and the lack of specific diagnostic markers,a considerable proportion of patients are diagnosed at advanced stages,rendering them ineligible for surgical interventions.Transcatheter arterial embolization(TAE)is an interventional therapeutic approach involving the insertion of a fine catheter via the femoral artery to reach the vasculature near the tumor site.TAE aims to obstruct the arterial supply to the tumor by deploying embolic agents,thereby inducing necrosis in cancer cells.This procedure is suitable for patients with good liver function and overall health,particularly those with large HCCs that have not invaded the portal vein[1,2].Nonetheless,

关键词： Transcatheter arterial embolization Fatigue Symptom distress Hepatocellular carcinoma Influencing factors

Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO yan-fang gu Shu-xiao CHAI Xin-lou School of Traditional Chinese Medicine Beijing University of Chinese Medicine

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol(LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor(LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9(PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

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Neural Regeneration Research 2025年第4期20卷 917-935页

作者： Dian Jiao Lai Xu Zhen gu Hua yan Dingding Shen Xiaosong gu Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjinChina Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang UniversityHangzhouZhejiang ProvinceChina Affiliated Hospital of Nantong University NantongJiangsu ProvinceChina

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

关键词： diagnosis drug treatment electroencephalography epilepsy monitoring epilepsy nerve regeneration neurostimulation non-drug interventions pathogenesis prediction

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Tau truncation in the pathogenesis of Alzheimer's disease: a narrative review

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Neural Regeneration Research 2024年第6期19卷 1221-1232页

作者： Dandan Chu Xingyue yang Jing Wang yan Zhou Jin-Hua gu Jin Miao Feng Wu Fei Liu Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products Coinnovation Center of Neuroregeneration Nantong University 2. Department of Pharmacology School of Pharmacy Nantong University 3. Department of Biochemistry and Molecular Biology School of Medicine Nantong University 4. Department of Clinical Pharmacy Affiliated Maternity and Child Health Care Hospital of Nantong University Nantong University 5. Laboratory of Animal Center Nantong University Department of Neurochemistry Inge Grundke-Iqbal Research Floor New York State Institute for Basic Research in Developmental Disabilities

Alzheimer’s disease is characterized by two major neuropathological hallmarks—the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubuleassociated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer’s disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics. In addition, Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner. This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments, investigates the role of specific truncations in physiological and pathological states of Alzheimer’s disease, and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer’s disease.

关键词： Alzheimer’s disease cleavage site diagnosis marker neurofibrillary tangles phosphorylation Tau Tau aggregation therapy truncation

Preparation and Characterization of Biobased Dehydroabietyl Polyethylene Glycol Glycidyl Ether-Grafted Hydroxyethyl Cellulose with High Emulsifying Property

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Journal of Renewable Materials 2024年第1期12卷 103-117页

作者： Zhengqing Ding Quan yang Xinyan yan Feng gu Xujuan Huang Zhaosheng Cai School of Chemical and Chemistry Yancheng Institute of TechnologyYancheng224051China

Dehydroabietyl polyethylene glycol glycidyl ether-grafted hydroxyethyl cellulose(HEC)polymer surfactant(DA(EO)5GE-g-HEC)was prepared using ring-opening polymerization with biobased rosin and hydroxyethyl cellulose as feedstocks.Dehydroabietyl polyethylene glycol glycidyl ether(DA(EO)5GE)was formed by condensation of dehydroabietyl alcohol polyoxyethylene ether(Rosin derivative:DA(EO)5H)and epichlorohydrin.The grafting degree of DA(EO)5GE-g-HEC was manipulated by adjusting the mass ratio of HEC and DA(EO)5GE and confirmed by EA.According to the formula,when m(HEC)/m(DA(EO)2GE)was 1:1~1:5,the grafting rate of DA(EO)5GE in DA(EO)5GE-g-HEC varied from 34.43%to 38.33%.The surface activity and foam properties of DA(EO)5GE-g-HEC aqueous solution were studied.The results showed that with the increase in grafting rate,the critical micellar concentration(CMC)in aqueous solution changed from 1.28 to 0.96 g/L.The results of the thermogravimetric analysis showed that the temperature range of the main stage of mass loss of DA(EO)5GE-g-HEC was 310°C~410°C,and the thermal decomposition processes of the samples with five mass ratios were similar.An oil in water emulsion was prepared by choosing cyclohexane as the oil phase and DA(EO)5GE-g-HEC as the emulsifier.The effect of DA(EO)5GE-g-HEC mass fraction on emulsion particle size and stability was analyzed.The results suggested that when the oil-water ratio was 8:2 with 0.4%emulsifier,the emulsion droplets were the smallest in terms of particle size and were the most stable.The rheological test results showed that the apparent viscosity decreased with the increase in shear rate and showed a typical elastic gel phenomenon.

关键词： Rosin hydroxyethyl cellulose surfactant emulsion rheological behaviour

Recombinant adeno-associated virus 8 vector in gene therapy:Opportunities and challenges

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Genes & Diseases 2024年第1期11卷 283-293页

作者： Liyuan Zhao Zixuan yang Minhui Zheng Lei Shi Mengyun gu Gang Liu Feng Miao yan Chang Fanghua Huang Naping Tang Anhui University of Traditional Chinese Medicine HefeiAnhui 230000China yangtze Delta Drug Advanced Research Institute Yangtze Delta Pharmaceutical CollegeNantongJiangsu226133China Shanghai Innostar Bio-Technology Co. LtdChina State Institute of Pharmaceutical IndustryShanghai 201203China Innostar Bio-tech Nantong Co. Ltd.NantongJiangsu 226133China Center for Drug Evaluation National Medical Products AdministrationBeijing 100022China

In recent years,significant breakthroughs have been made in the field of gene ther-apy.Adeno-associated virus(AAV)is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of interest.Among the AAV vectors,AAV serotype 8(AAv8)has attracted much attention for its efficient and stable gene transfection into specific tissues.Currently,recombinant AAv8 has been widely used in gene therapy research on a va-riety of diseases,including genetic diseases,cancers,autoimmune diseases,and viral diseases.

关键词： AAV8 Adeno-associated virus Gene therapy Primates

An endophytic fungus interacts with the defensinlike protein OsCAL1 to regulate cadmium allocation in rice

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Molecular Plant 2024年第2期17卷 312-324页

作者： Tianyu gu Ziai Qi Yating Wang Siying Chen Jing yan Huapeng Qiu yanxuan Yu Zjun Fang Junmin Wang Jiming Gong National Key Laboratory of Plant Molecular Genetics Shanghai Center for Plant Stress BiologyCAS Center for Excellence in Molecular Plant SciencesChinese AcademyofSciencesShanghai200032China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China University of the Chinese Academy of Sciences Beijing 100049China Hunan Key Laboratory of Economic Crops Genetic Improvement and Integrated Utilization College of Life ScienceHunan University of Science and TechnologyXiangtan411201China State Key Laboratory of Crop Stress Adaptation and Improvement School of Life SciencesHenan UniversityKaifeng 475004China Institute of Crops and Nuclear Technology Utilization Zhejiang Academy of Agricultural SciencesHangzhou 310021China

Defensin-like proteins are conserved in multicellular organisms and contribute to innate immune re-sponses against fungal pathogens.In rice,defensins play a novel role in regulating cadmium(Cd)efflux from the cytosol.However,whether the antifungal activity of defensins correlates with Cd-efflux function remains unknown.In this study,we isolated an endophytic Fusarium,designed Fo1o,by a comparative mi-crobiome analysis of rice plants grown in a paddy contaminated with Cd.Fo10 is tolerant to high levels of Cd,but is sensitive to the defensin-like protein OsCAL1,which mediates Cd efflux to the apoplast.We found that Fo10 symbiosis in rice is regulated by OsCAL1 dynamics,and Fo10 coordinates multiple plant pro-cesses,including Cd uptake,vacuolar sequestration,efflux to the environment,and formation of Fe pla-ques in the rhizosphere.These processes are dependent on the salicylic acid signaling pathway to keep Cd levels low in the cytosol of rice cells and to decrease Cd levels in rice grains without any yield penalty.Fo10 also plays a role in Cd tolerance in the poaceous crop maize and wheat,but has no observed effects in the eudicot plants Arabidopsis and tomato.Taken together,these findings provide insights into the mech-anistic basis underlying how afungal endophyte and host plant interact to control Cd accumulation in host plants by adapting defense responses to promotethe establishment ofa symbiosis that permits adaptation to high-Cd environments.

关键词： defensin-like protein Fusarium oxysporum endophyte cadmium allocation

Tunable VO_(2) cavity enables multispectral manipulation from visible to microwave frequencies

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Light(Science & Applications) 2024年第3期13卷 510-518页

作者： Hang Wei Jinxin gu Tao Zhao Zhiyuan yan He-Xiu Xu Shuliang Dou Cheng-Wei Qiu Yao Li Center for Composite Materials and Structure Harbin Institute of TechnologyHarbin 150001China National University of Singapore Department of Electrical&Computer EngineeringSingapore 117583Singapore School of Chemical Engineering and Technology Harbin Institute of TechnologyHarbin 150001China Suzhou Laboratory Suzhou 215123China

Optical materials capable of dynamically manipulating electromagnetic waves are an emerging field in memories,optical modulators,and thermal management.Recently,their multispectral design preliminarily attracts much attention,aiming to enhance their efficiency and integration of functionalities.However,the multispectral manipulation based on these materials is challenging due to their ubiquitous wavelength dependence restricting their capacity to narrow wavelengths.In this article,we cascade multiple tunable optical cavities with selective-transparent layers,enabling a universal approach to overcoming wavelength dependence and establishing a multispectral platform with highly integrated functions.Based on it,we demonstrate the multispectral(ranging from 400 nm to 3 cm),fast response speed(0.9 s),and reversible manipulation based on a typical phase change material,vanadium dioxide.Our platform involves tandem VO_(2)-based Fabry–Pérot(F-P)cavities enabling the customization of optical responses at target bands independently.It can achieve broadband color-changing capacity in the visible region(a shift of~60 nm in resonant wavelength)and is capable of freely switching between three typical optical models(transmittance,reflectance,and absorptance)in the infrared to microwave regions with drastic amplitude tunability exceeding 0.7.This work represents a state-of-art advance in multispectral optics and material science,providing a critical approach for expanding the multispectral manipulation ability of optical systems.

关键词： spectral microwave visible