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Anti-Parkinsonian Therapy:Strategies for Crossing the Blood–Brain Barrier and Nano-Biological Effects of Nanomaterials

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Nano-Micro Letters 2022年第6期14卷 350-398页

作者： guowang cheng Yujing Liu Rui Ma Guopan cheng Yucheng Guan Xiaojia Chen Zhenfeng Wu Tongkai Chen Key Laboratory of Modern Preparation of Traditional Chinese Medicine Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004People’s Republic of China Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou 510405People’s Republic of China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078People’s Republic of China

Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly prevalent.Unfortunately,there is no clinical cure for PD,and novel anti-PD drugs are therefore urgently required.However,the selective permeability of the blood–brain barrier(BBB)poses a huge challenge in the development of such drugs.Fortunately,through strategies based on the physiological characteristics of the BBB and other modifications,including enhancement of BBB permeability,nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB.Although nanomaterials are often used as carriers for PD treatment,their biological activity is ignored.Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects.In this review,we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment.Subsequently,we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects.Finally,we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field.Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.

关键词： Blood-brain barrier Parkinson’s disease Nasal delivery Biomimetic drug delivery Nano-biological effects

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Ultrasmall Coordination Polymers for Alleviating ROS-Mediated Inflammatory and Realizing Neuroprotection against Parkinson's Disease

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Research 2022年第4期2022卷 531-546页

作者： guowang cheng Xueliang Liu Yujing Liu Yao Liu Rui Ma Jingshan Luo Xinyi Zhou Zhenfeng Wu Zhuang Liu Tongkai Chen Yu Yang Key Laboratory of Modern Preparation of Traditional Chinese Medicine Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China Institute of Molecular Medicine(IMM) Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou 510405China School of Cellular and Molecular Medicine University of BristolBristol BS81THUK Institute of Functional Nano e Soft Materials Laboratory(FUNSOM) Soochow UniversitySuzhouJiangsu 215123China

Parkinson's disease(PD)is the second most common neurodegenerative disease globally,and there is currently no effective treatment for this condition.Excessive accumulation of reactive oxygen species(ROs)and neuroinflammation are major contributors to PD pathogenesis.Herein,ultrasmall nanoscale coordination polymers(NCPs)coordinated by ferric ions and natural product curcumin(Cur)were exploited,showing efficient neuroprotection by scavenging excessive radicals and suppressing neuroinflammation.In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse PD model,such ultrasmall Fe-Cur NCPs with prolonged blood circulation and BBB traversing capability could effectively alleviate oxidative stress,mitochondrial dysfunction,and inflammatory condition in the midbrain and striatum to reduce PD symptoms.Thus,this study puts forth a unique type of therapeutics-based NCPs that could be used for safe and efficient treatment of PD with potential in clinical translation.

关键词： inflammation pathogenesis clinical

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Biomimetic manganese-based theranostic nanoplatform for cancer multimodal imaging and twofold immunotherapy

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Bioactive Materials 2023年第1期19卷 237-250页

作者： Yuyue Zhao Yuanwei Pan Kelong Zou Zhou Lan guowang cheng Qiuying Mai Hao Cui Qianfang Meng Tongkai Chen Lang Rao Limin Ma Guangtao Yu Stomatological Hospital Southern Medical UniversityGuangzhou510280China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen518132China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and Faculty of EngineeringNational University of SingaporeSingapore119074Singapore Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou510405China Medical Research Center Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou510080China

The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment(TME)and inferior drug targeting.Herein,an active targeting TME nanoplatform capable of revising the immunosuppressive TME microenvironment is designed.Briefly,gold nanorods(GNRs)are covered with silica dioxide(SiO_(2))and then coated manganese dioxide(MnO_(2))to obtain GNRs@SiO_(2)@MnO_(2)(GSM).Myeloid-derived suppressor cells(MDSCs)membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO_(2)@MnO_(2)@MDSCs(GSMM).In this system,GSMM inherits active targeting TME capacity of MDSCs.The localized surface plasmon resonance of GNRs is developed in near-infraredⅡwindow by MnO_(2)layer coating,realizing NIR-Ⅱwindow photothermal imaging and photoacoustic imaging of GSMM.Based on the release of Mn^(2+)in acidic TME,GSMM can be also used for magnetic resonance imaging.In cancer cells,Mn^(2+)catalyzes H_(2)O_(2)into·OH for(chemodynamic therapy)CDT leading to activate cGAS-STING,but also directly acts on STING inducing secretion of typeⅠinterferons,pro-inflammatory cytokines and chemokines.Additionally,photothermal therapy and CDT-mediated immunogenic cell death of tumor cells can further enhance anti-tumor immunity via exposure of CRT,HMGB1 and ATP.In summary,our nanoplatform realizes multimodal cancer imaging and dual immunotherapy.

关键词： Biomimetic Manganese ions The second near-infrared window Cancer imaging Immunotherapy

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Melatonin decreases GSDME mediated mesothelial cell pyroptosis and prevents peritoneal fibrosis and ultrafiltration failure

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Science China(Life Sciences) 2024年第2期67卷 360-378页

作者： Hongxia Ruan Xuejuan Li Lina Zhou Zihan Zheng Rulin Hua Xu Wang Yuan Wang Yujie Fan Shuwen Guo Lihua Wang Shafiq ur Rahman Ziwei Wang Yuyuan Wei Shuangyan Yu Rongzhi Zhang Qian cheng Jie Sheng Xue Li Xiaoyan Liu Ruqiang Yuan Xiaoyan Zhang Lihong Chen guowang Xu Youfei Guan Jing Nie Hongqiang Qin Feng Zheng Advanced Institute for Medical Sciences Dalian Medical UniversityDalian 116044China Department of Nephrology Second HospitalDalian Medical UniversityDalian 116023China CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Chongqing International Institute for Immunology Chongqing 401320China Department of Nephrology Shenzhen HospitalSouthern Medical UniversityShenzhen 518101China Wuhu Hospital and Health Science Center East China Normal UniversityShanghai 200241China Peking University First Hospital Peking UniversityBeijing 100034China

Peritoneal fibrosis together with increased capillaries is the primary cause of peritoneal dialysis failure.Mesothelial cell loss is an initiating event for peritoneal fibrosis.We find that the elevated glucose concentrations in peritoneal dialysate drive mesothelial cell pyroptosis in a manner dependent on caspase-3 and Gasdermin E,driving downstream inflammatory responses,including the activation of macrophages.Moreover,pyroptosis is associated with elevated vascular endothelial growth factor A and C,two key factors in vascular angiogenesis and lymphatic vessel formation.GSDME deficiency mice are protected from high glucose induced peritoneal fibrosis and ultrafiltration failure.Application of melatonin abrogates mesothelial cell pyroptosis through a MT1R-mediated action,and successfully reduces peritoneal fibrosis and angiogenesis in an animal model while preserving dialysis efficacy.Mechanistically,melatonin treatment maintains mitochondrial integrity in mesothelial cells,meanwhile activating m TOR signaling through an increase in the glycolysis product dihydroxyacetone phosphate.These effects together with quenching free radicals by melatonin help mesothelial cells maintain a relatively stable internal environment in the face of high-glucose stress.Thus,Melatonin treatment holds some promise in preserving mesothelium integrity and in decreasing angiogenesis to protect peritoneum function in patients undergoing peritoneal dialysis.

关键词： melatonin mitochondria pyroptosis GSDME peritoneal fibrosis mTOR

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深度置信网络算法在公路边坡工程安全评价中的运用

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安全与环境学报 2024年第2期24卷 470-478页

作者：蒙国往程懿吴波叶华政刘家乐广西大学土木建筑工程学院南宁530004 特色金属材料与组合结构全寿命安全国家重点实验室南宁530004 东华理工大学土木与建筑工程学院南昌330013

针对传统边坡工程安全评价方法无法对边坡稳定性进行符合实际情况下工程安全评价的问题,提出一种基于深度置信网络(Deep Belief Networks,DBN)算法的公路边坡工程安全评价方法。首先,使用MATLAB建立模型;然后,对基于DBN算法的边坡稳定... 详细信息

针对传统边坡工程安全评价方法无法对边坡稳定性进行符合实际情况下工程安全评价的问题,提出一种基于深度置信网络(Deep Belief Networks,DBN)算法的公路边坡工程安全评价方法。首先,使用MATLAB建立模型;然后,对基于DBN算法的边坡稳定性安全评价方法进行研究;最后,使用DBN算法在莆炎高速公路项目中进行公路边坡工程安全评价。结果显示:(1)与反向传播(Back Propagation,BP)神经网络相比,DBN模型得到的预测值误差更小,精度更高,计算复杂度更低、可扩展性更强;(2)在实际工程中,DBN算法能够有效地对众多非线性因素共同作用下的公路边坡进行符合实际的安全评价。

关键词：安全工程边坡稳定深度置信网络(DBN)

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基于微信平台的中医内科学PCBL教学模式应用研究

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中国中医药图书情报杂志 2024年第2期48卷 221-224页

作者：程培育刘汶富琦徐咏梅杨国旺王笑民首都医科大学附属北京中医医院北京100010

探讨基于微信平台的以问题为中心(PBL)教学方法与以案例为基础(CBL)的教学方法联合使用(即PCBL教学模式)在中医内科学专业本科生教学中的应用效果。选取北京中医药大学2019级京华传承班及2020级京华传承班中医学专业本科学生共64名,分... 详细信息

探讨基于微信平台的以问题为中心(PBL)教学方法与以案例为基础(CBL)的教学方法联合使用(即PCBL教学模式)在中医内科学专业本科生教学中的应用效果。选取北京中医药大学2019级京华传承班及2020级京华传承班中医学专业本科学生共64名,分为观察组和对照组,观察组采用基于微信平台的PCBL教学模式,对照组采用传统教学方法,对2组基础理论知识和综合运用能力进行考核,并以问卷调查形式评价教学效果。结果表明,观察组基础理论知识及综合运用能力的考核成绩均优于对照组(P<0.05),观察组问卷调查满意度高于对照组(P<0.05)。基于微信平台的PCBL教学模式可激发学生学习的兴趣和主动性,有助于本科生临床思维能力的培养及教师教学水平提升。

关键词：以问题为中心的教学方法以案例为基础的教学方法微信平台中医内科学本科生教学

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A metabolome atlas of mouse brain on the global metabolic signature dynamics following short-term fasting

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4838-4849页

作者： Yaping Shao Zhenfa Fu Yanfeng Wang Zhaofei Yang Yushan Lin Song Li cheng cheng Min Wei Zheyi Liu guowang Xu Weidong Le Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases The First Affliated HospitalDalian Medical University193 Lianhe Road116021 DalianChina CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical PhysicsChinese Academy of Sciences457 Zhongshan Road116023 DalianChina Institute of Neurology Sichuan Academy of Medical Science-Sichuan Provincial HospitalMedical School of UESTC611731 ChengduChina

Calorie restriction(CR)or a fasting regimen is considered one of the most potent non-pharmacological interventions to prevent chronic metabolic disorders,ameliorate autoimmune diseases,and attenuate aging.Despite efforts,the mechanisms by which CR improves health,particularly brain health,are still not fully understood.Metabolic homeostasis is vital for brain function,and a detailed metabolome atlas of the brain is essential for understanding the networks connecting different brain regions.

关键词： fasting homeostasis diseases

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基于模糊理论的地铁深基坑非对称施工安全风险评估

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土木与环境工程学报（中英文） 2022年第5期44卷 8-15页

作者：吴波赵睿蒙国往陈辉浩黄惟刘家粱程懿广西大学土木建筑工程学院南宁530004 东华理工大学土木与建筑工程学院南昌330013 广州城建职业学院建筑工程学院广州510925

地铁深基坑非对称施工比一般深基坑工程施工难度更大、风险性更高。为合理有效地对地铁深基坑非对称施工工况进行风险评估,以广州某地铁深基坑工程为依托,构建了以围护结构、既有线车站非对称土压力、基坑环境、周围环境和现场安全管理... 详细信息

地铁深基坑非对称施工比一般深基坑工程施工难度更大、风险性更高。为合理有效地对地铁深基坑非对称施工工况进行风险评估,以广州某地铁深基坑工程为依托,构建了以围护结构、既有线车站非对称土压力、基坑环境、周围环境和现场安全管理为基准的风险评价指标体系。采用模糊层次分析法和多级模糊综合评判法,建立了地铁深基坑非对称施工的评估模型。由定量计算结果得到深基坑非对称施工在评价集中对应的风险等级,与实际工程情况相吻合。根据评估结果得到各指标所占权重大小,可采取相应措施来降低对应风险。

关键词：地铁深基坑非对称施工施工安全风险评估模糊理论

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三聚磷酸钠改性聚氨酯纳米粒子的合成及表征

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南京工业大学学报（自然科学版） 2016年第6期38卷 51-56页

作者：程爱民刁国旺扬州市职业大学生物与化工工程学院江苏扬州225009 扬州大学化学化工学院江苏扬州225002

以二苯基甲烷-4,4′-二异氰酸酯(MDI)、聚四氢呋喃醚二醇(PTMG)为主要原料,二羟基甲基丙酸(DMPA)作为功能单体,异丙醇作为封端剂,并以三乙胺中和,制得聚氨酯离聚物(PUI)。再用十二烷基硫酸钠溶液以及三聚磷酸钠(STP)溶液处理,制得表面... 详细信息

以二苯基甲烷-4,4′-二异氰酸酯(MDI)、聚四氢呋喃醚二醇(PTMG)为主要原料,二羟基甲基丙酸(DMPA)作为功能单体,异丙醇作为封端剂,并以三乙胺中和,制得聚氨酯离聚物(PUI)。再用十二烷基硫酸钠溶液以及三聚磷酸钠(STP)溶液处理,制得表面修饰的聚氨酯粒子(PUI-STP)。用透射电子显微镜(TEM)、扫描电子显微镜(SEM)、马尔文粒度分布仪、核磁共振仪(NMR)及X线光电子能谱仪(XPS)对样品进行表征。结果表明:粒子为圆球形,大小较为均一,平均粒径为179.2 nm,达到了纳米尺度,且PUI-STP中增加了大量P元素,说明三聚磷酸根已经被成功引入到聚氨酯纳米粒子表面。红细胞体外试验结果表明该纳米粒子具有良好的血液相容性,细胞毒性实验结果表明该纳米粒子具有良好的细胞相容性。

关键词：聚氨酯纳米粒子三聚磷酸钠细胞毒性实验

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SS304不锈钢焊接热输入过程中温度及残余应力分析

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铸造技术 2016年第8期37卷 1798-1800页

作者：邱国旺程文明南昌大学科学技术学院江西南昌330029 江西科技学院汽车工程学院江西南昌330098

结合高斯热源模型与圆柱热源模型,对SS304不锈钢在不同温度下的性能进行仿真和分析。在持续恒定的热输入情况下建立热源模型,通过仿真模拟焊接参数,分析焊接中温度和残余应力复杂的变化过程,得出材料在高温下的性能。

关键词： TIG焊热传导量有限元分析瞬态温度残余应力

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