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Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia lu Sijia Tian Yanmei Zhao Wenjie Ren Institute of Disaster and Emergency Medicine Tianjin UniversityTianjinChina Key Laboratory for Disaster Medicine Technology TianjinChina Henan Medical Key Laboratory for Research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical Center of Tissue Engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina Institutes of Health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells

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Identifying the dynamic behaviors in complete reconstruction of Co-based complex precatalysts during electrocatalytic oxygen evolution

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Journal of Energy Chemistry 2025年第1期100卷 226-233页

作者： Jingfang Zhang Danyang Wu Linke Cai Youluan lu Fanpeng Cheng Lijuan Shi Qun Yi Yao Liu Yi Huang Key Laboratory of Green Chemical Engineering Process of Ministry of Education Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education Hubei Key Laboratory of Novel Reactor and Green Chemical Technology School of Chemical Engineering & Pharmacy Wuhan Institute of Technology Key Laboratory of Pesticide & Chemical Biology of Ministry of Education Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction of Ministry of Education College of Chemistry Central China Normal University College of Materials Science and Engineering Fuzhou University

Transition metal-based nanomaterials have emerged as promising electrocatalysts for oxygen evolution reaction（OER）. Considerable research efforts have shown that self-reconstruction occurs on these nanomaterials under operating conditions of OER process. However, most of them undergo incomplete reconstruction with limited thickness of reconstruction layer, leading to low component utilization and arduous exploration of real catalytic mechanism. Herein, we identify the dynamic behaviors in complete reconstruction of Co-based complexes during OER. The hollow phytic acid（PA） cross-linked CoFe-based complex nanoboxes with porous nanowalls are designed because of their good electrolyte penetration and mass transport ability, in favor of the fast and complete reconstruction. A series of experiment characterizations demonstrate that the reconstruction process includes the fast substitution of PA by OH-to form Co（Fe）(OH)xand subsequent potential-driven oxidation to Co（Fe）OOH. The obtained CoFeOOH delivers a low overpotential of 290 mV at a current density of 10 mA cm-2and a long-term *** experiment results together with theory calculations reveal that the Fe incorporation can result in the electron rearrangement of reconstructed CoFeOOH and optimization of their electronic structure,accounting for the enhanced OER activity. The work provides new insights into complete reconstruction of metal-based complexes during OER and offers guidelines for rational design of high-performance electrocatalysts.

关键词： Complete reconstruction Co-based complex Precatalysts Oxygen evolution reaction

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岑溪地区10000名中学生心理健康现状及影响因素分析

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中国当代医药 2024年第24期31卷 131-134页

作者：唐华成赖飞翔李剑友林丽华卢贤萍广西壮族自治区岑溪市第三人民医院精神科广西岑溪543299

目的对岑溪地区10000名中学生的心理健康现状进行调查,并分析其影响因素,为中学生的心理健康干预提供依据。方法于2021年10月至2023年10月筛选岑溪地区10000名中学生作为研究对象,应用“石都心港”心理健康服务软件平台,采用90项症状清... 详细信息

目的对岑溪地区10000名中学生的心理健康现状进行调查,并分析其影响因素,为中学生的心理健康干预提供依据。方法于2021年10月至2023年10月筛选岑溪地区10000名中学生作为研究对象,应用“石都心港”心理健康服务软件平台,采用90项症状清单(SCL90)、患者健康问卷(PHQ-9)、焦虑自评量表(SAS)对入选的在校中学生进行心理测评,对所有研究对象的测评数据及时进行整理、汇总、记录,采用多元线性回归分析影响心理状态的因素。结果岑溪地区10000名中学生心理健康各量表得分总体偏高,SCL90评分为(62.35±4.21)分、PHQ-9评分(10.35±1.34)分、SAS评分为(58.34±4.69)分。不同年龄、性别、年级学生的SCL90、PHQ-9、SAS评分比较,差异有统计学意义(P<0.05)。多元线性回归分析结果显示,年龄≥15岁、女生、高中是中学生心理健康(SAS评分、SCL90得分、PHQ-9评分)的独立影响因素(P<0.05)。结论需重视中学生的心理健康,加强关注具有上述影响因素的学生,制订针对性、个性化干预措施。

关键词：中学生心理健康影响因素岑溪地区

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Efficacy and safety of chiglitazar,a novel peroxisome proliferatoractivated receptor pan-agonist,in patients with type 2 diabetes:a randomized,double-blind,placebo-controlled,phase 3 trial(CMAP)

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Science Bulletin 2021年第15期66卷 1571-1580,M0004页

作者： Linong Ji Weihong Song Hui Fang Wei Li Jianlin Geng Yangang Wang Lian Guo Hanqing Cai Tao Yang Hongmei Li Gangyi Yang Qifu Li Kuanzhi Liu Shuying Li Yanjun Liu Fuyan Shi Xinsheng Li Xin Gao Haoming Tian Qiuhe Ji Qing Su Zhiguang Zhou Wenbo Wang Zunhai Zhou Xuejun Li Yancheng Xu Zhiqiang Ning Haixiang Cao Desi Pan He Yao xianping lu Weiping Jia Peking University People’s Hospital Beijing 100044China Chenzhou No.1 People’s Hospital Chenzhou 423000China Tangshan Gongren Hospital Tangshan 063000China The Affiliated Hospital of Xuzhou Medical College Xuzhou 221006China Harrison International Peace Hospital Hengshui 053000China The Affiliate Hospital of Qingdao University Qingdao 266003China Chongqing Three Gorges Central Hospital Chongqing 404000China The Second Hospital of Jilin University Changchun 130041China Jiangsu Province Hospital Nanjing 210029China China Meitan General Hospital Beijing 100028China The Second Affiliate Hospital of Chongqing Medical University Chongqing 400010China The First Affiliate Hospital of Chongqing Medical University Chongqing 400016China The Third Hospital of Hebei Medical University Shijiazhuang 050051China Tianjin Medical University General Hospital Tianjin 300052China The 306th Hospital of PLA Beijing 100101China Baogang Hospital of Inner Mongolia Baotou 014010China Cangzhou’s Central Hospital Cangzhou 031706China Zhongshan Hospital Fudan University Shanghai 200032China Huaxi Hopsital of Sichuan University Chengdu 610041China The First Affiliated Hospital of The 4th Military Medical University Xi’an 710000China Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai 200092China The Second Xiangya Hospital of Central South University Changsha 410008China Peking University Shougang Hospital Beijing 100144China The Central Hospital of Yangpu District of Shanghai Shanghai 200090China The First Affiliate Hospital of Xiamen University Xiamen 361003China Zhongnan Hospital of Wuhan University Wuhan 430071China Shenzhen Chipscreen Biosciences Co. Ltd.Shenzhen 518057China Shanghai 6th People’s Hospital Shanghai 200233China

Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical *** randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise *** patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once *** primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over *** results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;Pluding glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar *** overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the *** incidences of mild edema and body weight gain were reported in the chiglitazar dose *** results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

关键词： Chiglitazar Carfloglitazar PPAR pan-agonist

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A Novel Self-Supervised Learning Network for Binocular Disparity Estimation

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 209-229页

作者： Jiawei Tian Yu Zhou Xiaobing Chen Salman A.AlQahtani Hongrong Chen Bo Yang Siyu lu Wenfeng Zheng Department of Computer Science and Engineering Major in Bio Artificial IntelligenceHanyang UniversityAnsan-si15577Republic of Korea School of Electrical and Computer Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of Computer Engineering College of Computer and Information SciencesKing Saud UniversityRiyadh11574Saudi Arabia School of Automation University of Electronic Science and Technology of ChinaChengdu610054China

Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical *** study proposes a novel end-to-end disparity estimation model to address these *** approach combines a Pseudo-Siamese neural network architecture with pyramid dilated convolutions,integrating multi-scale image information to enhance robustness against lighting *** study introduces a Pseudo-Siamese structure-based disparity regression model that simplifies left-right image comparison,improving accuracy and *** model was evaluated using a dataset of stereo endoscopic videos captured by the Da Vinci surgical robot,comprising simulated silicone heart sequences and real heart video *** results demonstrate significant improvement in the network’s resistance to lighting interference without substantially increasing ***,the model exhibited faster convergence during training,contributing to overall performance *** study advances endoscopic image processing accuracy and has potential implications for surgical robot applications in complex environments.

关键词： Parallax estimation parallax regression model self-supervised learning Pseudo-Siamese neural network pyramid dilated convolution binocular disparity estimation

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对产后抑郁症相关问题的探讨

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护理研究 2004年第2期18卷 109-111页

作者：黄仙萍王国兴鲁建英陈亚娜山东省济南市中心医院

随着围产医学的发展,孕产妇的心理保健已成为围产保健中一个不可忽视的部分.妊娠虽然是育龄妇女的一种正常、自然的生理现象,但对孕妇来说,毕竟是一次巨大的生理变化和心理应激过程.她们在经历怀孕、分娩、产后恢复及哺乳等一系列生理... 详细信息

随着围产医学的发展,孕产妇的心理保健已成为围产保健中一个不可忽视的部分.妊娠虽然是育龄妇女的一种正常、自然的生理现象,但对孕妇来说,毕竟是一次巨大的生理变化和心理应激过程.她们在经历怀孕、分娩、产后恢复及哺乳等一系列生理过程中,会产生各种心理、生理的变化,一旦某些改变的程度和性质超越了正常的变异界限,则成为病理性的改变.产后抑郁越来越受到人们的普遍关注.

关键词：产后抑郁症发病率抑郁症状产妇

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Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

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Neural Regeneration Research 2025年第8期20卷 2373-2381页

作者： Lifang Zhao Mingkai Zhang Qimeng Li Xuemin Wang Jie lu Ying Han Yanning Cai Department of Clinical Biobank Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Geriatric Medical Research Center BeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Radiology and Nuclear Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics BeijingChina Key Laboratory of Neurodegenerative diseases Ministry of EducationBeijingChina School of Biomedical Engineering Hainan UniversityHaikouHainan ProvinceChina Center of Alzheimer’s Disease Beijing Institute for Brain DisordersBeijingChina National Clinical Research Center for Geriatric Diseases BeijingChina Institute of Biomedical Engineering Shenzhen Bay LaboratoryGaoke Innovation CenterShenzhenGuangdong ProvinceChina Department of Neurobiology Xuanwu HospitalCapital Medical UniversityBeijingChina

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative ***,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°*** aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large *** samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline *** samples were stored at-80°C for up to 6 years before being used in this *** results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage ***,the level of total tau showed a negative correlation with sample storage ***,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage *** was not observed in individuals with cognitive ***,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage ***,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's ***,in cohort studies,it is important to consider the impact of storage time on the overall results.

关键词： Alzheimer’s disease amyloid-β diagnostic ability glial fibrillary acidic protein neurodegeneration neurofilament light chain plasma biomarkers single molecule array storage time tau

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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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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin lu Jianzhong Hu Yong Cao Chengjun Li Department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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High Fe‑Loading Single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

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Nano-Micro Letters 2025年第2期17卷 187-203页

作者： Si Chen Fang Huang Lijie Mao Zhimin Zhang Han Lin Qixin Yan Xiangyu lu Jianlin Shi Department of Cardiology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200092People’s Republic of China Shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 200050People’s Republic of China Shanghai Frontiers Science Center of Nanocatalytic Medicine School of MedicineTongji UniversityShanghai 200092People’s Republic of China

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site ***,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with *** constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial ***,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading ***,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/*** addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)*** in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound *** work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

关键词： Nanocatalytic medicine Single-atom catalysts Reactive oxygen species(ROS) High metal loading Oxidase catalysis

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