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Viral-mediated gene therapy in pediatric neurological disorders

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World Journal of Pediatrics 2024年第6期20卷 533-555页

作者： Jing Peng Wei-Wei Zou Xiao-Lei Wang Zhi-Guo Zhang Ran Huo Li yang Department of Pediatrics Clinical Research Center for Chidren Neurodevelopmental disablities of Hunan ProvinceXiangya HospitalCentral South UniversityChangsha 410008China Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefeiChina State Key Laboratory of Reproductive Medicine Nanjing Medical UniversityNanjingChina

Background Due to the broad application of next-generation sequencing,the molecular diagnosis of genetic disorders in pediatric neurology is no longer an unachievable ***,treatments for neurological genetic disorders in children remain primarily *** the other hand,with the continuous evolution of therapeutic viral vectors,gene therapy is becoming a clinical *** this perspective,we wrote this review to illustrate the current state regarding viral-mediated gene therapy in childhood neurological *** sources We searched databases,including PubMed and Google Scholar,using the keywords"adenovirus vector,""lentivirus vector,"and"AAv"for gene therapy,and"immunoreaction induced by gene therapy vectors,""administration routes of gene therapy vectors,"and"gene therapy"with"NCL,""SMA,""DMD,""congenital myopathy,""MPS""leukodystrophy,"or"pediatric metabolic disorders".We also screened the database of *** using the keywords"gene therapy for children"and then filtered the results with the ones aimed at neurological *** time range of the search procedure was from the inception of the databases to the *** We presented the characteristics of commonly used viral vectors for gene therapy for pediatric neurological disorders and summarized their merits and drawbacks,the administration routes of each vector,the research progress,and the clinical application status of viral-mediated gene therapy on pediatric neurological *** Viral-mediated gene therapy is on the brink of broad clinical ***-mediated gene therapy will dramatically change the treatment pattern of childhood neurological disorders,and many children with incurable diseases will meet the dawn of a ***,the vectors must be optimized for better safety and efficacy.

关键词： Gene therapy Neurological disorders Pediatrics Viral vectors

Genetic lineage tracing identifies adaptive mechanisms of pancreatic islet β cells in various mouse models of diabetes with distinct age of initiation

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Science China(Life Sciences) 2024年第3期67卷 504-517页

作者： Qi Fu Yu Qian Hemin Jiang Yunqiang He Hao Dai yang Chen Zhiqing Xia Yucheng Liang Yuncai Zhou Rui Gao Shuai Zheng Hui Lv Min Sun Kuanfeng Xu Tao yang Department of Endocrinology the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China

During the pathogenesis of type 1 diabetes(T1D) and type 2 diabetes(T2D), pancreatic islets, especially the β cells, face significant challenges. These insulin-producing cells adopt a regeneration strategy to compensate for the shortage of insulin, but the exact mechanism needs to be defined. High-fat diet(HFD) and streptozotocin(STZ) treatment are well-established models to study islet damage in T2D and T1D respectively. Therefore, we applied these two diabetic mouse models, triggered at different ages, to pursue the cell fate transition of isletβ cells. Cre-LoxP systems were used to generate islet cell type-specific(α, β, or δ) green fluorescent protein(GFP)-labeled mice for genetic lineage tracing, thereinto β-cell GFP-labeled mice were tamoxifen induced. Single-cell RNA sequencing(scRNA-seq) was used to investigate the evolutionary trajectories and molecular mechanisms of the GFP-labeled β cells in STZ-treated mice. STZ-induced diabetes caused extensive dedifferentiation of β cells and some of which transdifferentiated into α or δ cells in both youth-and adulthood-initiated mice while this phenomenon was barely observed in HFD models. β cells in HFD mice were expanded via self-replication rather than via transdifferentiation from α or δ cells, in contrast, α or δ cells were induced to transdifferentiate into β cells in STZ-treated mice(both youthand adulthood-initiated). In addition to the re-dedifferentiation of β cells, it is also highly likely that these “α or δ” cells transdifferentiated from pre-existing β cells could also re-trans-differentiate into insulin-producing β cells and be beneficial to islet recovery. The analysis of ScRNA-seq revealed that several pathways including mitochondrial function, chromatin modification, and remodeling are crucial in the dynamic transition of β cells. Our findings shed light on how islet β cells overcome the deficit of insulin and the molecular mechanism of islet recovery in T1D and T2D pathogenesis.

关键词： islet regeneration lineage tracing high fat diet(HFD) streptozotocin(STZ)

基于生态本底-格局-潜力框架的国土空间生态修复分区研究——以粤港澳大湾区为例

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热带地理 2024年第2期44卷 212-225页

作者：张伟龙闹李盛港王龙北京工业大学城市建设学部北京100124 广州市城市规划勘测设计研究院广州510060 广州市资源规划和海洋科技协同创新中心广州510060 广东省城市感知与监测预警企业重点实验室广州510060

文章以粤港澳大湾区为例,在生态系统服务评价、生态安全格局构建的基础上,尝试将生态恢复潜力、修复效率纳入研究范畴,建构了生态本底-格局-潜力的国土空间生态修复分区框架,通过生态优先修复区的识别实现修复效率的提升。结果表明:2010... 详细信息

文章以粤港澳大湾区为例,在生态系统服务评价、生态安全格局构建的基础上,尝试将生态恢复潜力、修复效率纳入研究范畴,建构了生态本底-格局-潜力的国土空间生态修复分区框架,通过生态优先修复区的识别实现修复效率的提升。结果表明:2010—2020年大湾区生态系统服务水平显著下降,自然恢复力良好与保护政策支持强的地区存在空间错配。以乡镇为单元进行生态修复分区,发现:1)生态维持区占总面积的7.7%,应以综合改善为主,促进经济与生态的可持续。2)生态保护区面积占44.5%,作为生态安全的底线区域,应以保护为主,加大政策管制力度。3)生态提升区面积占11.9%,应通过多样化、持续的维育措施为主,以强化区域生态网络的冗余度。4)生态修复区面积占35.9%,此中,优先修复区是拥有较高的自然恢复力与政策扶持的地区,应以实施长期、渐进式的修复工程为主;协同修复区拥有较高的自然恢复力,但政策支持力度不足,应当协同上级政府或区域联合治理,提升区域整体修复效率。

关键词：国土空间生态修复生态修复分区生态系统服务生态安全格局粤港澳大湾区

白骨顶的种内巢寄生行为及对不同类型寄生卵的反应

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野生动物学报 2024年第1期45卷 95-102页

作者：赵紫寒渠畅杨月周永青宗诚程鲲东北林业大学野生动物与自然保护地学院哈尔滨150040 生态环境部南京环境科学研究所南京210042 黑龙江三环泡国家级自然保护区管理局富锦156100

种内巢寄生是鸟类的条件性繁殖策略,具有特定的进化历史和地域特征。白骨顶(Fulica atra)作为古北界广泛分布的湿地水禽,其种内巢寄生和反寄生行为策略对于巢寄生理论假说的验证具有重要意义。通过模型卵和真卵放置试验,探究白骨顶对不... 详细信息

种内巢寄生是鸟类的条件性繁殖策略,具有特定的进化历史和地域特征。白骨顶(Fulica atra)作为古北界广泛分布的湿地水禽,其种内巢寄生和反寄生行为策略对于巢寄生理论假说的验证具有重要意义。通过模型卵和真卵放置试验,探究白骨顶对不同类型寄生卵的识别能力,并分析其繁殖期不同阶段的寄生防御策略。结果表明:白骨顶具有较高的种内巢寄生频率,拒卵行为包括埋卵、将寄生卵排出巢外等,对模型卵有较强的识别能力,尤其是深色模型卵未出现错误拒卵,而对于真卵的识别能力相对较弱,模型卵和真卵的拒卵成功率差异显著(χ^(2)=4.304,p=0.038)。不同繁殖阶段白骨顶的拒卵反应差别很大,在产卵期拒卵强度高于孵卵后,两个阶段的拒卵成功率差异极显著(χ^(2)=9.580,p=0.002)。白骨顶通过寄生卵识别和拒卵行为,减少种内巢寄生的影响,同时又权衡拒卵防御成本,在不同繁殖阶段采取有利于自身适合度的行为适应策略。

关键词：白骨顶种内巢寄生寄生卵模型卵卵识别

Dimensional regulation in gigantic molybdenum blue wheels featuring{(W)Mo_(5)}motifs for enhanced proton conductivity

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Nano Research 2024年第9期17卷 8261-8268页

作者： Yu-Lun Wu Jing Du Hai-Ying Zhang Ming-Jun Hou Qiao-Yue Li Wei-Chao Chen Kui-Zhan Shao Bo Zhu Chao Qin Xin-long Wang Zhong-Min Su Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education Department of ChemistryNortheast Normal UniversityChangchun 130024China Hebei Key Laboratory of Organic Functional Molecules National Demonstration Center for Experimental Chemistry EducationTesting and Analysis CenterCollege of Chemistry and Materials ScienceHebei Normal UniversityShijiazhuang 050024China State Key Laboratory of Supramolecular Structure and Materials Institute of Theoretical ChemistryCollege of ChemistryJilin UniversityChangchun 130021China

Dimensional regulation in polyoxometalates is an effective strategy during the design and synthesis of polyoxometalates-based high proton conductors,but it is not available to ***,the precise regulation of dimensionality has been realized in an unprecedented gigantic molybdenum blue wheel family featuring pentagonal{(W)Mo5}motifs through optimizing the molar ratio of Mo/W,including[Gd_(2)Mo_(124)W_(14)O_(422)(H_(2)O)62]38-(0D-{Mo_(124)W_(14)},1),[Mo_(126)W_(14)O441(H_(2)O)51]^(70-)(1D-{Mo_(126)W_(14)}n,2),and[Mo_(124)W_(14)O_(430)(H_(2)O)50]60-(2D-{Mo_(124)W_(14)}n,3).Such important{(W)Mo5}structural motif brings new reactivity into gigantic Mo blue *** are different numbers and sites of{Mo2}defects in each wheel-shaped monomer in 1-3,which leads to the monomers of 2 and 3 to form 1D and 2D architectures via Mo-O-Mo covalent bonds driven by{Mo2}-mediated H_(2)O ligands substitution process,respectively,thus achieving the controllable dimensional *** expected,the proton conductivity of 3 is 10 times higher than that of 1 and 1.7 times higher than that of *** continuous proton hopping sites in 2D network are responsible for the enhanced proton conductivity with lower activation *** study highlights that this dimensional regulation approach remains great potential in preparing polyoxometalates-based high proton conductive materials.

关键词： polyoxometalate molybdenum blue wheels Mo/W mixed-addenda polyoxometalates dimensional regulation proton conduction

Biomimetic fibril-like injectable hydrogels for wound management

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Biomedical Engineering Communications 2024年第2期3卷 26-27页

作者： Bo-Han Li Jin-Gai Jiang Si-Wen Du Hui-Juan cheng Yan-Ni Song Wei Shi Dong-Liang yang Key Laboratory of Flexible Electronics and Institute of Advanced Materials School of Physical and Mathematical SciencesNanjing Tech UniversityNanjing 211816China

Soft tissue repair and regeneration present a significant clinical *** hydrogels have emerged as a promising solution for promoting stem cell differentiation and facilitating soft tissue formation[1].Various materials,including synthetic polymers like polydimethyl siloxane and natural polymers like proteins,have been be used as hydrogel matrix for hydrogel preparation[2,3].However,the limited biodegradability,inhomogeneous network structure,and inadequate mechanical properties of these hydrogels hinder their long-term application in complex environments in *** by the nanostructure of collagen fibrils,Li et *** a strategy for creating injectable nanofibrillar hydrogels by combining self-assembly and chemical crosslinking of nanoparticles[4].Moreover,injectable hydrogels offer advantages as implantable materials,including better defect filling and reduced risk of infection compared to prefabricated hydrogels[5].

关键词： hydrogel inhomogeneous crosslinking

Conservation genomic investigation of an endangered conifer,Thuja sutchuenensis,reveals low genetic diversity but also low genetic load

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Plant Diversity 2024年第1期46卷 78-90页

作者： Tongzhou Tao Richard IMilne Jialiang Li Heng yang Shiyang Wang Sihan Chen Kangshan Mao Key Laboratory for Bio-Resource and Eco-Environment of Ministry of Education&Sichuan Zoige Alpine Wetland Ecosystem National Observation and Research Station College of Life ScienceSichuan UniversityChengduChina Institute of Molecular Plant Science School of Biological ScienceUniversity of EdinburghEdinburgh EH93BFUK College of Science Tibet UniversityLhasa 850000Xizang Autonomous RegionPR China

Endangered species generally have small populations with low genetic diversity and a high genetic *** sutchuenensis is an endangered conifer endemic to southwestern *** was once considered extinct in the wild,but in 1999 was ***,little is known about its genetic *** collected 67 individuals from five wild,isolated *** populations,and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in *** to delineate the conservation units of ***,based on whole transcriptome sequencing data,as well as target capture sequencing *** found that populations of *** could be divided into three *** groups had low levels genetic diversity and were moderately genetically *** findings also indicate that *** suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial *** Thuja species,*** presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying ***,distribution of fitness effects analysis indicated a high extinction risk for *** lines of evidence identified three management units for *** *** possesses a low genetic load,low genetic diversity,suboptimal fitness,and anthropogenic pressures all present an extinction risk for this rare *** might also hold true for many endangered plant species in the mountains all over the world.

关键词： Sichuan Arborvitae Genetic load Deleterious mutations Demographic history Conservation genomics

Effect of Meteorological Data Assimilation on Regional Air Quality Forecasts over the Korean Peninsula

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Journal of Meteorological Research 2024年第2期38卷 262-284页

作者： Yunjae CHO Hyun Mee KIM Eun-Gyeong yang Yonghee LEE Jae-Bum LEE Soyoung HA Department of Atmospheric Sciences Yonsei UniversitySeoul 03722Republic of Korea Air Quality Forecasting Center National Institute of Environmental ResearchIncheon 22689Republic of Korea National Center for Atmospheric Research BoulderCO 80305USA University of Maryland Baltimore County BaltimoreMD 21250USA Global Modeling and Assimilation Office NASA Goddard Space Flight CenterGreenbeltMD 20771USA

The Weather Research and Forecasting model coupled with Chemistry(WRF-Chem),a type of online coupled chemistry-meteorology model(CCMM),considers the interaction between air quality and meteorology to improve air quality *** data assimilation(DA)can be used to reduce uncertainty in meteorological field,which is one factor causing prediction uncertainty in the *** this study,WRF-Chem and three-dimensional variational DA were used to examine the impact of meteorological DA on air quality and meteorological forecasts over the Korean *** nesting model domains were configured over East Asia(outer domain)and the Korean Peninsula(inner domain).Three experiments were conducted by using different DA domains to determine the optimal model domain for the meteorological *** the meteorological DA was performed in the outer domain or both the outer and inner domains,the root-mean-square error(RMSE),bias of the predicted particulate matter(PM)concentrations,and the RMSE of predicted meteorological variables against the observations were smaller than those in the experiment where the meteorological DA was performed only in the inner *** indicates that the improvement of the synoptic meteorological fields by DA in the outer domain enhanced the meteorological initial and boundary conditions for the inner domain,subsequently improving air quality and meteorological *** to the experiment without meteorological DA,the RMSE and bias of the meteorological and PM variables were smaller in the experiments with *** effect of meteorological DA on the improvement of PM predictions lasted for approximately 58-66 h,depending on the ***,the uncertainty reduction in the meteorological initial condition by the meteorological DA contributed to a reduction of the forecast errors of both meteorology and air quality.

关键词： meteorological data assimilation regional air quality forecast particulate matter concentration optimal model domain forecast error WRF-Chem

All-inorganic nitrate electrolyte for high-performance lithium oxygen battery

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Nano Research 2024年第5期17卷 4163-4170页

作者： Dongyue yang Jiayi Du Kai Chen Haoran Zhang Gang Huang Tong Liu Xinbo Zhang Hongjie Zhang State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China

Lithium-oxygen(Li-O_(2))batteries have been regarded as an expectant successor for next-generation energy storage systems owing to their ultra-high theoretical energy ***,the comprehensive properties of the commonly utilized organic salt electrolyte are still unsatisfactory,not to mention their expensive prices,which seriously hinders the practical production and application of Li-O_(2) ***,we have proposed a low-cost all-inorganic nitrate electrolyte(LiNO_(3)-KNO_(3)-DMSO)for Li-O_(2) *** inorganic nitrate electrolyte exhibits higher ionic conductivity and a wider electrochemical stability window than the organic salt *** existence of K+can stabilize the O_(2)-intermediate,promoting the discharge process through the solution pathway with an enlarged *** at an ultra-low concentration of 0.01 M,the K+can still remain stable to promote the solution discharge process and also possess a new function of inhibiting the dendrite growth by electrostatic shielding,further enhancing the battery stability and contributing to the long cycle *** a result,in the 0.99 M LiNO_(3)-0.01 M KNO_(3)-DMSO electrolyte,the Li-O_(2) batteries exhibit prolonged cycling performance(108 cycles)and excellent rate performance(2 A·g^(-1)),significantly superior to the organic salt one.

关键词： Li-O_(2)batteries potassium ions inorganic nitrate electrolyte solution pathway mechanism