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High-resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer's disease mice

National Science Review 2019年第6期6卷 1223-1238页

作者： Xiaochuan Zhang xianzhen yin Jingjing Zhang Anan Li Hui Gong Qingming Luo Haiyan Zhang Zhaobing Gao Hualiang Jiang School of Pharmacy East China University of Science and Technology CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and Technology MoE Key Laboratory for Biomedical Photonics School of Engineering Sciences Huazhong University of Science and Technology Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and TechnologyShanghai Tech University

Accumulating evidence indicates the critical importance of cerebrovascular dysfunction in the pathogenesis of Alzheimer’s disease(AD). However, systematic comparative studies on the precise brain vasculature of wild-type and AD model mice are still rare. Using an image-optimization method for analysing Micro-Optical Sectioning Tomography(MOST) data, we generated cross-scale whole-brain 3 D atlases that cover the entire vascular system from large vessels down to smallest capillaries at submicron resolution,for both wild-type mice and a transgenic(APP/PS1) mouse model of AD. In addition to distinct vascular patterns in different brain regions, we found that the main vessels of the molecular layer of the hippocampal dentate gyrus(DG-ml) undergo abrupt changes in both diameter and branch angle, spreading a unique comb-like pattern of capillaries. By using a quantitative analysis workflow, we identified in the hippocampus of AD mice an overall reduction of the mean vascular diameter, volume fraction and branch angle, with most significant impairment in the DG-ml. In addition, virtual endoscopy revealed irregular morphological features in the vessel lumen of the AD mice, potentially contributing to the impairment of blood flow. Our results demonstrate the capability of high-resolution cross-scale evaluation of brain vasculature and underscore the importance of studying hippocampal microcirculation for understanding AD pathogenesis.

关键词： Micro-Optical Sectioning Tomography image optimization Alzheimer’s disease impaired hippocampal vasculature virtual vascular endoscopy

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Simultaneous 3D Visualization of the Microvascular and Neural Network in Mouse Spinal Cord Using Synchrotron Radiation Micro-Computed Tomography

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Neuroscience Bulletin 2021年第10期37卷 1469-1480页

作者： Liyuan Jiang Chengjun Li Miao Li xianzhen yin Handing Wu Chunyue Duan Yong Cao Hongbin Lu Jianzhong Hu Department of Spine Surgery Xiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangsha 410008China Department of Sports Medicine Xiangya HospitalCentral South UniversityChangsha 410008China Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre Changsha 410008China Hunan Engineering Research Center of Sport and Health Changsha 410008China Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with ***,ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still *** this study,we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography(SRμCT)to visualize the 3D neurovascular network in the mouse spinal *** our method,the 3D neurons,nerve fibers,and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive ***,we found that the 3D morphology of neurons,nerve fiber tracts,and vasculature visualized by SRjiCT were highly consistent with that visualized using the histological ***,the 3D neurovascular structure could be quantitatively evaluated by the combined *** method shown here will be useful in fundamental neuroscience studies.

关键词： Srμct 3D High-resolution Neurovascular Spinal cord

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Multi-dimensional visualization for the morphology of lubricant stearic acid particles and their distribution in tablets

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Asian Journal of Pharmaceutical Sciences 2020年第1期15卷 60-68页

作者： Liu Zhang Shailendra Shakya Li Wu Jiangtao Wang Guanghui Jin Huimin Sun xianzhen yin Lixin Sun Jiwen Zhang School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Weihai Disu Pharmaceutical Manufacturer Weihai 264200China National Institutes for Food and Drug Control Beijing 100050China

The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid(SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional(3 D) information of SA particles in tablets was detected by a quantitative and non-invasive 3 D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography(SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA(GUT), reprocessed SA(GRT), as well as reference listed drug(RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.

关键词： Stearic acid Morphology Spatial distribution SR-μCT Glipizide tablets

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Three dimensional distribution of surfactant in microspheres revealed by synchrotron radiation X-ray microcomputed tomography

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Asian Journal of Pharmaceutical Sciences 2017年第4期12卷 326-334页

作者： Li Wu Manli Wang Vikramjeet Singh Haiyan Li Zhen Guo Shuangying Gui Peter York Tiqiao Xiao xianzhen yin Jiwen Zhang Center for Drug Delivery Systems Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201210China School of Pharmaceutical Sciences Anhui University of Chinese MedicineHefei 230038China Institute of Pharmaceutical Innovation University of BradfordBradfordWest Yorkshire BD7 1DPUnited Kingdom Shanghai Synchrotron Radiation Facility Shanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201204China

This study investigated the formulation mechanism of microspheres via internal surfactant distribution. Eudragit L100 based microspheres loaded with bovine serum albumin were prepared by solid in oil in oil emulsion solvent evaporation method using acetone and liquid paraffin system containing sucrose stearate as a surfactant. The fabricated microspheres were evaluated for encapsulation efficiency, particle size, production yield, and in vitro release characteristics. The internal structures of microspheres were characterized using synchrotron radiation X-ray microcomputed tomography(SR-μCT). The enhanced contrast made the sucrose stearate distinguished from Eudragit to have its three dimensional(3D) distribution. Results indicated that the content and concentration determined the state of sucrose stearate and had significant influences on the release kinetics of protein. The dispersity of sucrose stearate was the primary factor that controlled the structure of the microspheres and further affected the encapsulation efficiency, effective drug loading, as well as in vitro release behavior. In conclusion, the 3D internal distribution of surfactant in microspheres and its effects on protein release behaviors have been revealed for the first time. The highly resolved 3D architecture provides new evidence for the deep understanding of the microsphere formation mechanism.

关键词： Three dimensional Synchrotron radiation X-ray microcomputed tomography Distribution Microsphere Sucrose stearate

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Synchrotron radiation-based Fourier-transform infrared spectromicroscopy for characterization of the protein/peptide distribution in single microspheres

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Acta Pharmaceutica Sinica B 2015年第3期5卷 270-276页

作者： Manli Wang Xiaolong Lu xianzhen yin Yajun Tong Weiwei Peng Li Wu Haiyan Li Yan Yang Jingkai Gu Tiqiao Xiao Min Chen Jiwen Zhang School of Pharmaceutical Sciences Anhui University of Chinese Medicine Center for Pharmaceutical Preparations Shanghai Institute of Materia MedicaChinese Academy of Sciences School of Mechanical Engineering Shanghai Institute of Technology Shanghai Synchrotron Radiation Facility Shanghai Institute of Applied PhysicsChinese Academy of Sciences College of Life Sciences Jilin University

The present study establishes a visualization method for the measurement of the distribution and localization of protein/peptide constituents within a single poly-lactide-co-glycolide (PLGA) microsphere using synchrotron radiation based Fourier-transform infrared speciiomlcroscopy (SR-FTIR). The representative infrared wavenumbers specific for protein/peptide (Exenatide) and excipient (PLGA) were identified and chemical maps at the single microsphere level were generated by measuring and plotting the intensity of these specific bands. For quantitative analysis of the distribution within microspheres, Matlab soft are was used to transform the map file into a 3D matrix and the matiix values specific for the drug and excipient were extracted. Comparison of the normalized SR- FM maps of PLGA and Exenatide indicated that PLGA was unit-on-lily distributed, while Exenatide was relatively non-uniformly distributed in the microspheres. In conclusion, SR-FTIR is a rapid, nondestructive and sensitive detection technology to provide the distribution of chemical constituents and functional groups in microparticles and microspheres. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia 'Medico, Chinese Academy of 'Medical Sciences. Production and hosting by Elsevier B.V.

关键词： Fourier-transform infrared spectromicroscopy Micerosphere Exenatide PLGA

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Optimization of taste-masking on ibuprofen microspheres with selected structure features

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Asian Journal of Pharmaceutical Sciences 2019年第2期14卷 174-182页

作者： Wei Qin Yuanzhi He Zhen Guo Liu Zhang Li Wu xianzhen yin Shailendra Shakya Abi Maharjan Yan Tang Weifeng Zhu Jiwen Zhang Ministry of Education Jiangxi University of Traditional Chinese Medicine Shanghai Institute of Materia Medica Chinese Academy of Sciences School of Pharmacy Shenyang Pharmaceutical University School of Pharmacy University of Chinese Academy of Sciences

The microsphere was a primary particulate system for taste-masking with unique structural features defined by production process. In this article, ibuprofen lipid microspheres of octadecanol and glycerin monostearate were prepared to mask the undesirable taste of ibuprofen via three kinds of spray congealing processes, namely, air-cooling, water-cooling and citric acid solution-cooling. The stereoscopic and internal structures of ibuprofen microspheres were quantitatively analyzed by synchrotron radiation X-ray micro-computed tomography(SR-μCT) to establish the relationship between the preparation process and microsphere architectures. It was found that the microstructure and morphology of the microspheres were significantly influenced by preparation processes as the primary factors to determine the release profiles and taste-masking effects. The sphericity of ibuprofen microspheres congealed in citric acid solution was higher than that of other two and its morphology was more regular than that being congealed in air or distilled water, and the contact angles between congealing media and melted ibuprofen in octadecanol and glycerin monostearate well demonstrated the structure differences among microspheres of three processes which controlled the release characteristics of the microspheres. The structure parameters like porosity, sphericity, and radius ratio from quantitative analysis were correlated well with drug release behaviors. The results demonstrated that the exterior morphology and internal structure of microspheres had considerable influences on the drug release behaviors as well as taste-masking effects.

关键词： Ibuprofen microsphere Spray congealing Internal structure Synchrotron radiation X-ray micro-computed tomography

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Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2568-2577页

作者： Abi Maharjan Hongyu Sun Zeying Cao Ke Li Jinping Liu Jun Liu Tiqiao Xiao Guanyun Peng Junqiu Ji Peter York Balmukunda Regmi xianzhen yin Jiwen Zhang Li Wu Center for Drug Delivery System Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationYantai UniversityYantai 264005China University of Chinese Academy of Sciences Beijing 100049China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China Shanghai Synchrotron Radiation Facility/Zhangjiang Lab Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201204China Hefei Lifeon Medication Group Hefei 230088China Center for MOST and Image Fusion Analysis Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201210China Maharajgung Medical Campus Institute of MedicineTribhuvan UniversityKathmandu 44606Nepal

Defining and visualizing the three-dimensional(3 D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3 D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography(SR-μCT). In situ formed 3 D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3 D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral“roadways”. Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed3 D microstructures, a “subterranean river model” for the drug release mechanism has been defined to explain the drug release mechanism.

关键词： Bilayer osmotic pump tablet Synchrotron radiation micro-computed tomography Three-dimensional microstructure Release kinetics Void formation Peripheral“roadways” Push-pull model Subterranean river model

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Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats

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Acta Pharmaceutica Sinica B 2022年第1期12卷 326-338页

作者： Hongyu Sun Siyu He Li Wu Zeying Cao Xian Sun Mingwei Xu Shan Lu Mingdi Xu Baoming Ning Huimin Sun Tiqiao Xiao Peter York Xu Xu xianzhen yin Jiwen Zhang School of Chemical and Environmental Engineering Shanghai Institute of TechnologyShanghai 201418China Center for Drug Delivery System Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China School of Materials Science and Engineering Center for Supramolecular Chemistry and CatalysisDepartment of ChemistryShanghai UniversityShanghai 200444China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China National Institutes for Food and Drug Control Beijing 100050China Shanghai Synchrotron Radiation Facility/Zhangjiang Lab Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201204China Center for MOST and Image Fusion Analysis Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201210China

Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic *** this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of *** structures of pellets in solid state and in vitro compendium media were *** in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium ***,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in *** sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,*** adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,*** magnesium pellets behaved *** structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.

关键词： Internal 3D structure 3D reconstruction Structural parameter Enteric coated pellets Synchrotron radiation X-ray micro computed tomography In vivo and in vitro structure correlation Esomeprazole magnesium Omeprazole magnesium

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Structural and functional imaging of brains

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Science China Chemistry 2023年第2期66卷 324-366页

作者： Zhichao Liu ying Zhu Liming Zhang Weiping Jiang Yawei Liu Qiaowei Tang Xiaoqing Cai Jiang Li Lihua Wang Changlu Tao xianzhen yin Xiaowei Li Shangguo Hou Dawei Jiang Kai Liu Xin Zhou Hongjie Zhang Maili Liu Chunhai Fan Yang Tian Shanghai Key Laboratory of Green Chemistry and Chemical Processes School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai200241China Interdisciplinary Research Center Shanghai Synchrotron Radiation FacilityZhangjiang LaboratoryShanghai Advanced Research InstituteChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai201210China State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Chinese Academy of SciencesWuhan National Laboratory for OptoelectronicsWuhan430071China State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun130022China Department of Chemistry Tsinghua UniversityBeijing100084China School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative MoleculesInstitute of Translational MedicineShanghai Jiao Tong UniversityShanghai200240China Interdisciplinary Center for Brain Information Brain Cognition and Brain Disease InstituteShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen518055China Lingang Laboratory Shanghai201602China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai200240China Institute of Systems and Physical Biology Shenzhen Bay LaboratoryShenzhen518055China Department of Nuclear Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Analyzing the complex structures and functions of brain is the key issue to understanding the physiological and pathological *** neuronal morphology and local distribution of neurons/blood vessels in the brain have been known,the subcellular structures of cells remain challenging,especially in the live *** addition,the complicated brain functions involve numerous functional molecules,but the concentrations,distributions and interactions of these molecules in the brain are still poorly *** this review,frontier techniques available for multiscale structure imaging from organelles to the whole brain are first overviewed,including magnetic resonance imaging(MRI),computed tomography(CT),positron emission tomography(PET),serial-section electron microscopy(ss EM),light microscopy(LM)and synchrotron-based X-ray microscopy(XRM).Specially,XRM for three-dimensional(3D)imaging of large-scale brain tissue with high resolution and fast imaging speed is ***,the development of elegant methods for acquisition of brain functions from electrical/chemical signals in the brain is *** particular,the new electrophysiology technologies for neural recordings at the single-neuron level and in the brain are also *** also focus on the construction of electrochemical probes based on dual-recognition strategy and surface/interface chemistry for determination of chemical species in the brain with high selectivity and long-term stability,as well as electrochemophysiological microarray for simultaneously recording of electrochemical and electrophysiological signals in the ***,the recent development of brain MRI probes with high contrast-to-noise ratio(CNR)and sensitivity based on hyperpolarized techniques and multi-nuclear chemistry is ***,multiple optical probes and instruments,especially the optophysiological Raman probes and fiber Raman photometry,for imaging and biosensing in live brain are emphas

关键词： brain structure brain function brain chemistry chemical signal biosensing and bioimaging

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家乡的龙王山

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中国土族 2010年第3期 21-22页

作者：殷咸珍

在绵延起伏、莽莽苍苍的祁连山东麓,便是横亘于滔滔大通河南岸的大坂山。这里有一座巍峨嶙峋的高山,它就是大阪山的支脉——位于我家乡的龙王山。龙王山海拔4242米,是离我家最近也是最高的一座大山。在我二十五岁的时候,曾陪着父亲和叔... 详细信息

在绵延起伏、莽莽苍苍的祁连山东麓,便是横亘于滔滔大通河南岸的大坂山。这里有一座巍峨嶙峋的高山,它就是大阪山的支脉——位于我家乡的龙王山。龙王山海拔4242米,是离我家最近也是最高的一座大山。在我二十五岁的时候,曾陪着父亲和叔叔,攀登过它的峰顶。三十五年过去了,父亲和叔叔都已作古。

关键词：龙王山父亲土观活佛天池金刚寺森林公园宗教改革原生态大坂山锯子北山峡谷泽林卧龙佑宁寺

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