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Recent Strategies and Advances in Hydrogel-Based Delivery Platforms for Bone Regeneration

NANO-MICRO LETTERS 2025年第1期17卷 1-51页

作者： Wang, Xiao zeng, Jia Gan, Donglin Ling, Kun He, Mingfang Li, Jianshu Lu, Yongping Guangyuan Cent Hosp Sci & Technol Innovat Ctr Biomed Mat & Clin Res Guangyuan Key Lab Multifunct Med Hydrogel Guangyuan 628000 Peoples R China Nanjing Normal Univ Jiangsu Collaborat Innovat Ctr Biomed Funct Mat Sch Chem & Mat Sci Jiangsu Key Lab Biofunct Mat Nanjing 210023 Peoples R China Sichuan Univ Coll Polymer Sci & Engn State Key Lab Polymer Mat Engn Chengdu 610065 Peoples R China

Recent advances in the combined delivery platform that integrate nano-/microscale carriers and with 3D hydrogel network for bone regeneration are *** strategies for bioactive molecules delivery involving nanoparticles, nanosheets, and microspheres, along with extra stimuli such as near-infrared light, temperature changes, ultrasonication, and inflammatory conditions, are *** prospects and challenges for the clinical translation and the development of nano-/microscale incorporated hydrogel-based delivery platform are discussed. Bioactive molecules have shown great promise for effectively regulating various bone formation processes, rendering them attractive therapeutics for bone regeneration. However, the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo. Hydrogels have emerged as ideal carriers to address these challenges, offering the potential to prolong retention times at lesion sites, extend half-lives in vivo and mitigate side effects, avoid burst release, and promote adsorption under physiological conditions. This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration, encompassing applications in cranial defect repair, femoral defect repair, periodontal bone regeneration, and bone regeneration with underlying diseases. Additionally, this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery, carrier-assisted delivery, and sequential delivery. finally, this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.

关键词： Hydrogel Bone regeneration Bioactive molecules Drug delivery Nano-/microscale carriers

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Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

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Neural Regeneration Research 2025年第3期20卷 821-835页

作者： Jing Wang Bing Zhang Lanfang Li Xiaomei Tang Jinyu zeng Yige Song Chao Xu Kai Zhao Guoqiang Liu Youming Lu Xinyan Li Kai Shu Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Neurosurgery Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Pathophysiology School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Institute for Brain Research Wuhan Center of Brain ScienceHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Graduate Student Chongqing Medical UniversityChongqingChina Department of Basic Medicine School of Medical ScienceHubei University for NationalitiesEnshiHubei ProvinceChina Department of Anatomy School of Basic Medicine and Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive ***,the mechanism underlying this neurogenesis impairment remains *** this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain *** results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and *** with repetitive traumatic brain injuryalso showed deficits in spatial memory ***,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was *** inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological *** findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

关键词： complement C1 dendrite dentate gyrus hippocampus neural stem cell neurogenesis neuroinflammation neurological function neuron traumatic brain injury

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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

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Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

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Neural Regeneration Research 2025年第11期20卷 3193-3206页

作者： Ling-Xiao Yi Hui Ren Woon Genevieve Saw Li zeng Eng King Tan Zhi Dong Zhou National Neuroscience Institute Singapore Nanyang Technology University Singapore Department of Neurology Singapore General HospitalSingapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

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The potential mechanism and clinical application value of remote ischemic conditioning in stroke

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Neural Regeneration Research 2025年第6期20卷 1613-1627页

作者： Yajun Zhu Xiaoguo Li Xingwei Lei Liuyang Tang Daochen Wen Bo zeng Xiaofeng Zhang Zichao Huang Zongduo Guo The first Affiliated Hospital of Chongqing Medical University ChongqingChina

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

关键词： Akt apoptosis autophagy cerebral perfusion cerebral vascular stenosis clinical transformation hemorrhagic stroke ischemic stroke neuroinflammation neuroprotection Notch1 PI3K remote ischemic conditioning stroke

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Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 557-573页

作者： Jiewen Chen Xiaolin zeng Le Wang Wenwu Zhang Gang Li Xing Cheng Peiqiang Su Yong Wan Xiang Li Department of Spine Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Province Key Laboratory of Orthopedics and Traumatology GuangzhouGuangdong ProvinceChina

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord *** and astrocytes play key roles in the spinal cord injury micro-environment and share a close ***,the mechanisms involved remain *** this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming *** expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord *** vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between *** further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling ***,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling *** vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function ***,Gas6 may play a role in the treatment of spinal cord *** can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

关键词： astrocytes Axl cell polarization Gas6 Hippo signal inflammatory micro-environment intercellular interaction microglia single-cell sequencing spinal cord injury

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Mesospheric tide comparisons at low latitudes observed by two collocated meteor radars

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Earth and Planetary Physics 2025年第1期9卷 54-68页

作者： Jian Li Wen Yi XiangHui Xue Jie zeng HaiLun Ye JianYuan Wang JinSong Chen Na Li TingDi Chen Chinese Academy of Sciences(CAS)Key Laboratory of Geospace Environment Department of Geophysics and Planetary SciencesUniversity of Science and Technology of ChinaHefei 230026China CAS Center for Excellence in Comparative Planetology Anhui Mengcheng Geophysics National Observation and Research StationUniversity of Science and Technology of ChinaHefei 230026China Hefei National Laboratory University of Science and Technology of ChinaHefei 230026China Collaborative Innovation Center of Astronautical Science and Technology Harbin 150001China National Key Laboratory of Electromagnetic Environment China Research Institute of Radiowave PropagationQingdao 266107China Yunnan Kunming Electromagnetic Environment National Observation and Research Station Qujing Kunming 655000China

Accurate knowledge of mesospheric winds and waves is essential for studying the dynamics and climate in the mesosphere and lower thermosphere(MLT)*** this study,we conduct a comparative analysis of the mesosphere tidal results obtained from two adjacent meteor radars at low latitudes in Kunming,China,from November 2013 to December *** two radars operate at different frequencies of 37.5 MHz and 53.1 MHz,***,overall good agreement is observed between the two radars in terms of horizontal winds and tide *** results show that the dominant tidal waves of the zonal and meridional winds are diurnal and semidiurnal ***,we conduct an exhaustive statistical analysis to compare the tidal amplitudes and vertical wavelengths recorded by the dual radar systems,which reveals a high degree of alignment in tidal *** investigation includes variances and covariances of tidal amplitudes,which demonstrate remarkable consistency across measurements from both *** finding highlights clear uniformity in the mesospheric tidal patterns observed at low latitudes by the two neighboring meteor *** of the comparative analysis specifically underscore the significant correlation in vertical wavelength measurements,validating the robustness of radar observations for tidal research.

关键词： mesosphere and lower thermosphere region meteor radar mesospheric winds tides

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Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration Research 2025年第11期20卷 3259-3272页

作者： Huidong Li faqin Li Zhaoyi Chen Erwen Wu Xiaoxi Dai Danni Li Haojie An Shiyi zeng Chunyan Wang Li Yang Cheng Long School of Life Sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of Life Sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission

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Potassium ions and cyano group modified g-C3N4 for effective generation of H2O2 through two-electron oxygen reduction

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Science China Chemistry 2025年第1期 192-200页

作者： Dongying Wang Shulan Pu Yongmin Chen Ke Lei Yujie Duan Linjiao Mao Xuhui zeng Xi Luo Yuntao Zhang Yuqin Dong Jin Zhong Zhang Yan Sun School of Mechanical Engineering Chengdu University Department of Chemistry and Biochemistry University of California

Potassium ions （K+） doped graphitic carbon nitride （g-C3N4） was prepared by a thermal etching method using potassium hydroxide （KOH） as an ion *** transform infrared spectroscopy （fTIR） and X-ray photoelectron spectroscopy （XPS）results showed that the generation of the cyano group was detected while introducing K+.Under simulated sunlight irradiation,the sample with a K+doping amount of 10%showed the highest hydrogen peroxide （H2O2） generation rate of2,140.2μmol *** apparent quantum yield （AQY） at 400 nm and the solar-to-chemical conversion （SCC） are 4.35%and1.23%,respectively.K+acted as a bridge between g-C3N4layers,which enhanced charge transfer ***,the cyano group enhanced the adsorption capacity of protons （H+） and promoted the yield of *** catalyst exhibited excellent photocatalytic stability based on four-cycle *** addition,a mechanism study showed that superoxide radicals （·O2-）were the most important active species in the reaction *** production of H2O2was achieved through consecutive single-electron *** study deepens the understanding of the oxygen reduction reaction process and opens up a new venue for improving H2O2generation.

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实体法视角下低龄未成年人“核准追诉”的理解与展开

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河南财经政法大学学报 2025年第1期40卷 129-143页

作者：曾聪中国政法大学刑事司法学院北京100088

《刑法》第十七条第三款规定的“核准追诉”并非纯粹的程序法要件,而是同时具备实体法意涵。就逻辑前提而言,立法者并未以“个别下调刑事责任年龄”的法律拟制路径改变应负刑事责任的“一般人形象”,只是在极端个案中赋予司法机关具体... 详细信息

《刑法》第十七条第三款规定的“核准追诉”并非纯粹的程序法要件,而是同时具备实体法意涵。就逻辑前提而言,立法者并未以“个别下调刑事责任年龄”的法律拟制路径改变应负刑事责任的“一般人形象”,只是在极端个案中赋予司法机关具体证明个别刑事责任年龄以下者具备刑事责任能力的权力。就权力性质而言,核准追诉权不是以“是否有必要惩罚低龄未成年人”的需罚性考量为中心的自由裁量权,而是以“惩罚低龄未成年人是否正当”的应罚性判断为中心的例外反证权。实体法要件不能独立解决应罚性问题,多数观点完全切割程序法要件与实体法要件的做法不能成立,司法机关应当根据低龄未成年人是否在家庭、学校等具体场景进行充足的法律社会化为根据,补足刑事责任能力的具体证明,这正是“核准追诉”在实体法有责性层面的具体意涵。

关键词：低龄未成年人核准追诉实体法意涵例外反证说法律社会化

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