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Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases

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Nano-Micro Letters 2024年第12期16卷 233-284页

作者： Qingdong bao Xiaoting Zhang Zhankun Hao Qinghua Li Fan Wu Kaiyuan wang yang Li Wenlong Li Hua Gao State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyEye Institute of Shandong First Medical UniversityQingdao 266071People’s Republic of China State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002People’s Republic of China Eye Hospital of Shandong First Medical University Jinan 250021People’s Republic of China College of Ophthalmology Shandong First Medical UniversityJinan 250000People’s Republic of China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore

The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal *** drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and *** microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug ***,a comprehensive review of PSMNs in ophthalmology has not been published to *** this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug *** provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and *** also describe recent advances and the performance of various PSMNs in both research and clinical ***,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

关键词： Ocular delivery Polysaccharide Microneedles Drug administration

Hydrodynamic resistance of pore–throat structures and its effect on shale oil apparent permeability

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International Journal of Coal Science & Technology 2024年第2期11卷 101-110页

作者： Wendong wang Qian Zhang Jilong Xu Da Zheng lifeng Liu Yuliang Su Key Laboratory of Unconventional Oil and Gas Development Ministry of EducationQingdao 266580China School of Petroleum Engineering China University of Petroleum(East China)Qingdao 266580ShandongChina Petrochina Oil Gas and New Energies CompanyBeijing 100083China Research institute of Petroleum Exploration and Development PetroChinaBeijing 100083China

Oil transport is greatly affected by heterogeneous pore–throat structures present in *** is therefore very important to accurately characterize pore–throat ***,it remains unclear how pore–throat structures affect oil transport *** this paper,using finite element(FE)simulation and mathematical modeling,we calculated the hydrodynamic resistance for four pore–throat *** addition,the influence of pore throat structure on shale oil permeability is *** to the results,the hydrodynamic resistance of different pore throat structures can vary by 3.0%.The contribution of additional resistance caused by streamline bending is also in excess of 40%,even without slip ***-thermore,Pore–throat structures can affect apparent permeability by more than 60%on the REV scale,and this influence increases with heterogeneity of pore size distribution,organic matter content,and organic matter ***,modeling shale oil flow requires consideration of porous–throat structure and additional resistance,otherwise oil recovery and flow capacity may be overestimated.

关键词： Pore–throat structure Hydrodynamic resistance Apparent permeability REV-scale Shale oil

A new method of identifying and locating gross errors——Quasi-accurate detection

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chinese Science Bulletin 1999年第23期44卷 2200-2204页

作者： OU Jikuninstitute of geodesy and geophysics , IMboratory of Dynamical geodesy , chinese academy of Sciences , wuhan 43.077 , china institute of geodesy and geophysics Laboratory of Dynamical Geodesy Chinese Academy of Sciences Wuhan 430077 China

A new idea and a distinctive method have been proposed, which concern real errors and their estimators. By using the idea of 'Quasi-Stable Adjustment' created by Prof. Zhou Jiangwen for reference, the rank-deficient equations on real errors are resolved by adding the conditions under which the minimum of the norm of the real errors of the quasi-accurate observations is restrained.

关键词： least squares (LS) detection of gross errors (or outliers) hypothesis test robust estimation real errors.

Multi-level coarse-grained discrete element method modeling of cylinder particle flow in a rotating drum

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Particuology 2024年第5期88卷 218-238页

作者： Lei Xu Xiukai Wu Shuai wang Shiyi bao institute of Process Equipment and Control Engineering Zhejiang University of TechnologyHangzhou 310023China Engineering Research Center of Process Equipment and Remanufacturing Ministry of EducationZhejiang University of TechnologyHangzhou 310023China College of Mechanical Engineering Zhejiang University of TechnologyHangzhou 310023China State Key Laboratory of Clean Energy Utilization Zhejiang UniversityHangzhou 310027China

The coarse-grained discrete element method(DEM)is probably a feasible option for simulating an actual drum-type biomass boiler,which contains over 10 million cylinder particles.A multi-level study was conducted based on particle and coarse-grained level data to evaluate the adequacy of the coarse-grained approach in terms of geometrical characteristics,kinematic features,and dynamic *** scaling laws for contact parameters were used and compared during the *** results show that the coarse-grained approach can accurately predict the positions of the free surface and active-passive interface,the mixing index,and the orientation *** in the velocity fields may occur due to the worse flowability of coarse-grained particles near the free *** efficiency is significantly improved by the coarse-grained model compared with the corresponding original case(the same DEM code without a coarse-grained model was used for the original simulations).

关键词： Coarse-grained method Discrete element method(DEM) Cylinder particle Rotating drum Granular flow

Low-latitude hydroclimate changes related to paleomagnetic variations during the Holocene in coastal southern china

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Frontiers of Earth Science 2024年第2期18卷 324-335页

作者： Tingwei ZHANG Xiaoqiang yang Jian YIN Qiong CHEN Jianfang HU lu wang Mengshan JU Qiangqiang wang School of Earth Science and Engineering/Guangdong Provincial Key Laboratory of Geodynamics and Geohazards/Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Sun Yat-sen UniversityGuangzhou 510275China institute of Cultural Heritage Shandong UniversityQingdao 266237China State Key Laboratory of Organic Geochemistry Guangzhou Institute of GeochemistryChinese Academy of SciencesGuangzhou 510640China College of Urban and Environmental Sciences Peking UniversityBeijing 100871China institute of Oceanology Chinese Academy of SciencesQingdao 266071China

The variations in precipitation have displayed a complex pattern in different regions since the *** formation processes may have a significant impact on precipitation,especially during the tropical marine processes and summer monsoon which convey abundant water vapor to coastal southern china and inland ***,we use two 7500 year sedimentary records from the Pearl River Delta and the closed Maar Lake,respectively,in coastal southern china to reconstruct the mid-to-late-Holocene humidity variability and explore its possible relationship with cloud cover modulated by the Earth’s magnetic fields(EMF).Our proxy records document an apparent increase in wetness in coastal southern china between 3.0 and 1.8 kyr *** apparent increase in humidity appears to be consistent with the lower virtual axial dipole moments and,in turn,with a lower *** correlation suggests that the EMF might have been superimposed on the weakened monsoon to regulate the mid-to-late-Holocene hydroclimate in coastal southern china through the medium of galactic cosmic rays,aerosols,and cloud ***,further investigations are needed to verify this interaction.

关键词： hydroclimate variations Earth’s magnetic field coastal southern china the Holocene epoch

Generation of mitochondrial replacement monkeys by female pronucleus transfer

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Zoological Research 2024年第2期45卷 292-298页

作者： Chun-yang Li Xing-Chen Liu Yu-Zhuo Li Yan wang Yan-Hong Nie Yu-Ting Xu Xiao-Tong Zhang yong {3. Qiang Sun institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Genetic Evolution and Animal Models Chinese Academy of SciencesKunming 650201China University of chinese academy of Sciences Beijing 100049China

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe *** replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA *** pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously *** this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear *** individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during *** successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

关键词： Non-human primates Mitochondrial replacement Female pronuclear transfer

Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai bao lu Xu yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian {3. Shipeng Guo Jing Zhang Zhe {3. Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

Hierarchical crystalline-amorphous nanocomposites with high strength and large deformability enabled by elemental diffusion

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Journal of Materials Science & Technology 2024年第4期171卷 150-161页

作者： Liqiang wang Heyi wang Xin Zhou Huangliu Fu James Utama Surjadi Shuo Qu Xu Song Rong Fan yang lu Department of Mechanical Engineering City University of Hong KongHong KongChina Nano-Manufacturing Laboratory(NML) Shenzhen Research Institute of City University of Hong KongShenzhen 518057China Chengdu Research institute City University of Hong KongChengdu 610200China Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China Department of Mechanical and Automation Engineering The Chinese University of Hong KongHong KongChina Department of Mechanical Engineering The University of Hong KongHong KongChina

Amorphous/nanocrystalline dual-phase structures have recently emerged as an effective way for over-coming the strength-ductility trade-offand breaking the limitation of the reverse Hall-Petch ***,we proposed a new strategy to develop a hierarchical and interconnected amorphous-crystalline nanocomposite arising from the nanoscale elemental interdiffusion and oxygen adsorption behavior dur-ing thermal treatment *** nanocomposite consisted of a three-dimensional(3.)hierarchical network structure where the crystalline phase(Cr-Co-Ni-Al)was embedded into the Al-O-based amor-phous phase network with critical feature sizes encompassing three orders of magnitude(from microm-eter to nanometer scale).It can achieve ultrahigh compression yield strength of-3.6 GPa with large homogeneous deformation of over 50%*** massive interstitial atoms induced lattice distortion and hierarchical amorphous phase boundary contributed to the strength *** situ Uniaxial compression inside a transmission electron microscope(TEM)revealed that the exceptional deformability of the nanocomposites resulted from the homogenous plastic flow of nano-sized amorphous phase and the plastic co-deformation behavior restricted by the nano-architected dual-phase *** proposed dual-phase synthesis approach can outperform conventional nanolaminates design strategies in terms of the mechanical properties achievable while providing a pathway to easily tune the microstructure of these nanolaminates.

关键词： Nanolaminates Dual-phase nanocomposites In situ transmission electron microscopy Multi-component alloy

Optimization of Gas-Flooding Fracturing Development in Ultra-Low Permeability Reservoirs

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Fluid Dynamics & Materials Processing 2024年第3期20卷 595-607页

作者： lifeng Liu Menghe Shi Jianhui wang Wendong wang Yuliang Su Xinyu Zhuang Tight Oil Research institute PetroChina Research Institute of Petroleum Exploration&DevelopmentBeijing100083China Key Laboratory of Unconventional Oil&Gas Development China University of Petroleum(East China)Qingdao266580China Oil&Gas Technology Research institute Changqing Oilfield CompanyXi’an710018China

Ultra-low permeability reservoirs are characterized by small pore throats and poor physical properties, which areat the root of well-known problems related to injection and production. In this study, a gas injection floodingapproach is analyzed in the framework of numerical simulations. In particular, the sequence and timing of fracturechanneling and the related impact on production are considered for horizontal wells with different fracturemorphologies. Useful data and information are provided about the regulation of gas channeling and possible strategiesto delay gas channeling and optimize the gas injection volume and fracture parameters. It is shown that inorder to mitigate gas channeling and ensure high production, fracture length on the sides can be controlled andlonger fractures can be created in the middle by which full gas flooding is obtained at the fracture location in themiddle of the horizontal well. A Differential Evolution (DE) algorithm is provided by which the gas injectionvolume and the fracture parameters of gas injection flooding can be optimized. It is shown that an improvedoil recovery factor as high as 6% can be obtained.

关键词： Ultra-low permeability reservoir gas injection flooding component simulation fracture parameters intelligent optimization differential evolution