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Nanoparticles for the treatment of spinal cord injury

Neural Regeneration Research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun Department of Orthopedic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

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Versatile and efficient mammalian genome editing with Type I-C CRISPR System of Desulfovibrio vulgaris

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Science China Life Sciences 2024年

作者： Pan Li Dingcai Dong Fei Gao Yuyang Xie Honglin Huang Siwei Sun Zhao Ma Cheng He Jinsheng Lai Xuguang Du Sen wu State Key Laboratory of Animal Biotech Breeding College of Biological SciencesNational Engineering Laboratory for Animal BreedingFrontiers Science Center for Molecular Design BreedingChina Agricultural University College of Veterinary Medicine China Agricultural University Sanya Institute of China Agricultural University State Key Laboratory of Maize Bio-breeding National Maize Improvement CenterDepartment of Plant Genetics and BreedingChina Agricultural University Frontiers Science Center for Molecular Design Breeding China Agricultural University Center for Crop Functional Genomics and Molecular Breeding China Agricultural University

CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a *** type I CRISPR systems in Class I may offer greater specificity and versatility,they are not well-developed for genome ***,we present an alternative type I-C CRISPR system from Desulfovibrio vulgaris (Dvu) for efficient and precise genome editing in mammalian cells and *** optimized the Dvu type I-C editing complex to generate precise deletions at multiple loci in various cell lines and pig primary fibroblast cells using a paired PAM-in crRNA *** edited pig cells can serve as donors for generating transgenic cloned *** Dvu type I-C editor also enabled precise large fragment replacements with homology-directed ***,we adapted the Dvu-Cascade effector for cytosine and adenine base editing,developing Dvu-CBE and Dvu-ABE *** systems efficiently induced C-to-T and A-to-G substitutions in human genes without double-strand ***-target analysis confirmed the high specificity of the Dvu type I-C *** findings demonstrate the Dvu type I-C editor′s potential for diverse mammalian genome editing applications,including deletions,fragment replacement,and base editing,with high efficiency and specificity for biomedicine and agriculture.

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Luteolin， a common flavone in vegetables， acts as a hormetin possessing neurotrophic function: signaling mediated by inducing mitochondrial stress

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Food Science and Human Wellness 2024年

作者： Alex Xiong Gao Tracy Chenxi Xia Maggie Suisui Guo Gary Kawing Yuen Kevin Qiyun wu Tina Tingxia Dong Karl Wah-Keung Tsim Shenzhen Key Laboratory of Edible and Medicinal Bioresources， HKUST Shenzhen Research Institute Division of Life Science and Center for Chinese Medicine， The Hong Kong University of Science and Technology

This study aims to uncover the hormetic process of luteolin， a common dietary flavone， in neuronal cells through its role in inducing mitochondrial stress. In rat pheochromocytoma PC12 cells， luteolin at low concentrations caused a mild and reversible loss of mitochondrial membrane potential (MMP)， while high concentrations of luteolin triggered intense and sustained depolarization of MMP. The MMP disturbance was shown to have a close association with the trophic and/or toxic effects triggered by luteolin; because the common mitochondrial uncouplers shared similar bi-phase dose-response on cell viability， as that of luteolin. Along with the induced MMP pertubation， luteolin triggered the development of autophagy and mitophagy， as determined by mCherry-GFP-LC3B tandem protein， and by the co-localization of mitochondrial/lysosomal staining. Subsequent application of autophagy inhibitors in the cultures blocked the luteolin-induced neurotrophic activities and sensitized the cells to be less resistant to luteolin-mediated cytotoxicity. Other flavonoids also displayed similar properties in the cultures， indicating that these compounds act as hormetic pharmacological inducers that stimulate cells to become more resilient and adapt to threats. This study provides a unifying mechanistic explanation for the neuro-beneficial effects of luteolin and other flavonoids.

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RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3-and FADD-mediated cell death

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Cellular & Molecular Immunology 2024年第1期21卷 80-90页

作者： Xiaoxue Deng Lingxia Wang Yunze Zhai Qiuyue Liu Fengxue Du Yu Zhang Wenxing Zhao Tingtao wu Yiwen Tao Jie Deng Yongbing Cao Pei Hao Jiazi Ren Yunli Shen Zuoren Yu Yuejuan Zheng Haibing Zhang Haikun Wang State Key Laboratory of Cardiology Shanghai East HospitalTongji University School of MedicineShanghai200120China CAS Key Laboratory of Molecular Virology and Immunology Shanghai Institute of Immunity and InfectionChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai200031China CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200031China The Research Center for Traditional Chinese Medicine Shanghai Institute of Infectious Diseases and BiosecurityShanghai University of Traditional Chinese MedicineShanghai201203China Institute of Vascular Disease Shanghai TCM-Integrated HospitalShanghai University of Traditional Chinese MedicineShanghai200433China

Regulatory T(T_(reg))cells play an essential role in maintaining immune balance across various physiological and pathological ***,the mechanisms underlying T_(reg)homeostasis remain incompletely ***,we report that RIPK1 is crucial for T_(reg) cell survival and *** generated mice with T_(reg) cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell *** conventional T cells,Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent ***,simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death ***,our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis,thereby providing novel insights into the mechanisms of Treg cell homeostasis.

关键词： Treg cell Homeostasis Apoptosis Necroptosis

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钢壳沉管隧道耐火极限标准与防火保护技术研究——以深中通道沉管隧道为例

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隧道建设（中英文） 2024年第2期44卷 257-265页

作者：吴梦军吴庆良宋神友曹鹏招商局重庆交通科研设计院有限公司重庆400067 公路隧道国家工程研究中心重庆400067 西南大学工程技术学院重庆400715 深中通道管理中心广东中山528400

为提高我国超大断面钢壳沉管隧道火灾防控水平,以深中通道海底沉管隧道为例,采用热力耦合模拟和材性试验等方法开展钢壳沉管隧道耐火极限标准研究,考虑到龙骨、拼缝等防火构造薄弱环节,进行管节结构和管节接头耐火试验,并提出相应的防... 详细信息

为提高我国超大断面钢壳沉管隧道火灾防控水平,以深中通道海底沉管隧道为例,采用热力耦合模拟和材性试验等方法开展钢壳沉管隧道耐火极限标准研究,考虑到龙骨、拼缝等防火构造薄弱环节,进行管节结构和管节接头耐火试验,并提出相应的防火保护技术方案。主要结论如下:1)管节结构的耐火极限标准为火灾时,应将结构内侧钢壳最高温度控制在300℃以内;2)OMEGA橡胶管节接头的耐火极限标准为OMEGA橡胶超过70℃的时间小于2 h,超过100℃的时间小于1 h,且最高温度不得超过150℃;3)GINA橡胶管节接头的耐火极限标准为GINA橡胶超过100℃的时间小于1 h,且最高温度不得超过150℃;4)管节结构可采用35 mm单层防火板L型拼缝,对接面涂热膨胀胶;5)管节接头可采用35 mm防火板+50 mm陶瓷纤维毯双层防火保护体系,龙骨自由端取500 mm,拼缝处采用防火胶封堵。

关键词：深中通道沉管隧道钢壳混凝土结构耐火极限耐火试验防火保护

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α1-COP modulates plasmodesmata function through sphingolipid enzyme regulation

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Journal of Integrative Plant Biology 2024年第8期66卷 1639-1657页

作者： Arya Bagus Boedi Iswanto Minh Huy Vu Jong Cheol Shon Ritesh Kumar Shuwei wu Hobin Kang Da-Ran Kim Geon Hui Son Woe Yoen Kim Youn-Sig Kwak Kwang Hyeon Liu Sang Hee Kim Jae-Yean Kim Division of Applied Life Science(BK21 FOUR Program) Plant Molecular Biology and Biotechnology Research CenterGyeongsang National UniversityJinju 52828Korea College of Pharmacy and Research Institute of Pharmaceutical Sciences Kyungpook National UniversityDaegu 702-701Korea Departement of Plant Medicine Gyeongsang National UniversityJinju 52828Korea Division of Life Science Gyeongsang National UniversityJinju 52828Korea

Callose,aβ-1,3-glucan plant cell wall polymer,regulates symplasmic channel size at plasmodesmata(PD)and plays a crucial role in a variety of plant ***,elucidating the molecular mechanism of PD callose homeostasis is *** screened and identified an Arabidopsis mutant plant with excessive callose deposition at PD and found that the mutated gene wasα1-COP,a member of the coat protein I(COPI)coatomer *** report that loss of function ofα1-COP elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme Pd *** process is linked to the functions of ERH1,an inositol phosphoryl ceramide synthase,and glucosylceramide synthase through physical interactions with theα1-COP ***,the loss of function ofα1-COP alters the subcellular localization of ERH1 and GCS proteins,resulting in a reduction of Glc Cers and Glc HCers molecules,which are key sphingolipid(SL)species for lipid raft *** findings suggest thatα1-COP protein,together with SL modifiers controlling lipid raft compositions,regulates the subcellular localization of GPI-anchored PDBG2 proteins,and hence the callose turnover at PD and symplasmic movement of *** findings provide the first key clue to link the COPI-mediated intracellular trafficking pathway to the callose-mediated intercellular signaling pathway through PD.

关键词： callose coatomer proteins membrane-bound vesicle plasmodesmata sphingolipid enzymes

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Autocatalytic bifunctional supramolecular hydrogels for osteoporotic bone repair

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National Science Review 2024年第07期 263-278页

作者： Zhihui Han Xiang Gao Yuanjie Wang Cheng Huang Hao Song Shuning Cheng Xiaoyuan Yang Xiaoliang Cui Jie wu Kailu Wei Liang Cheng Institute of Functional Nano&Soft Materials(FUNSOM) Collaborative Innovation Center of Suzhou Nano Science and TechnologySoochow University Department of Orthopedics The Second Affiliated Hospital of Soochow University Macao Institute of Materials Science and Engineering Macau University of Science and Technology

Conventional bone scaffolds, which are mainly ascribed to highly active osteoclasts and an inflammatory microenvironment with high levels of reactive oxygen species and pro-inflammatory factors, barely satisfy osteoporotic defect repair. Herein, multifunctional self-assembled supramolecular fiber hydrogels(Ce–Aln gel) consisting of alendronate(Aln) and cerium(Ce) ions were constructed for osteoporotic bone defect repair. Based on the reversible interaction and polyvalent cerium ions, the Ce–Aln gel, which was mainly composed of ionic coordination and hydrogen bonds, displayed good injectability and autocatalytic amplification of the antioxidant effect. In vitro studies showed that the Ce–Aln gel effectively maintained the biological function of osteoblasts by regulating redox homeostasis and improved the inflammatory microenvironment to enhance the inhibitory effect on osteoclasts. Ribonucleic acid(RNA) sequencing further revealed significant downregulation of various metabolic pathways, including apoptosis signaling,hypoxia metabolism and tumor necrosis factor-alpha(TNF-α) signaling via the nuclear factor kappa-B pathway after treatment with the Ce–Aln gel. In vivo experiments showed that the clinical drug-based Ce–Aln gel effectively promoted the tissue repair of osteoporotic bone defects by improving inflammation and inhibiting osteoclast formation at the defect. Notably, in vivo systemic osteoporosis was significantly ameliorated, highlighting the strong potential of clinical translation for precise therapy of bone defects.

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Self-Adaptive and Electric Field-Driven Protective Layer with Anchored Lithium Deposition Enable Stable Lithium Metal Anode

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Energy & Environmental Materials 2024年第03期 36-44页

作者： Ting Chen Luchao Yue Guoqiang Shu Qing Yang Dong Wang Ruoyang Wang Xianyan Qiao Yan Sun Benhe Zhong Zhenguo wu Xiaodong Guo Department of Chemical Engineering Sichuan University School of Mechanical Engineering Chengdu University

Lithium metal battery has great development potential because of its lowest electrochemical potential and highest theoretical capacity. However,the uneven deposition of Li+flux in the process of deposition and stripping induces the vigorous growth of lithium dendrites,which results in severely battery performance degradation and serious safety hazards. Here,the tetragonal BaTiO3polarized by high voltage corona was used to build an artificial protective layer with uniform positive polarization direction,which enables uniform Li+flux. In contrast to traditional strategies of using protective layer,which can guide the uniform deposition of lithium *** ferroelectric protective layer can accurately anchor the Li+and achieve bottom deposition of lithium due to the automatic adjustment of the electric field. Simultaneously,the huge volume changes caused by Li+migration change of the lithium metal anode during charging and discharging is functioned to excite the piezoelectric effect of the protective layer,and achieve seamless dynamic tuning of lithium deposition/*** dynamic effect can accurately anchor and capture Li+. Finally,the layermodified Li anode enables reversible Li plating/stripping over 1500 h at1 mA cm-2and 50℃ in symmetric cells. In addition,the assembled Li-S full cell exhibits over 300 cycles with N/P≈1.35. This work provides a new perspective on the uniform Li+flux at the Li-anode interface of the artificial protective layer.

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冠状动脉腔内影像指导药物涂层球囊治疗合并血小板减少的ACS患者1例

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中华心血管病杂志 2024年第9期52卷 1106-1109页

作者：吴迅金琴花解放军总医院第一医学中心心血管内科北京100853

血小板减少患者发生急性冠脉综合征时, 加用抗血小板药物会增加出血风险。因此在行介入治疗时越来越倾向于单纯药物涂层球囊治疗的"介入无置入"方案。腔内影像指导在药物涂层球囊治疗原发血管病变中具有重要的临床意义。该文报道1例合... 详细信息

血小板减少患者发生急性冠脉综合征时, 加用抗血小板药物会增加出血风险。因此在行介入治疗时越来越倾向于单纯药物涂层球囊治疗的"介入无置入"方案。腔内影像指导在药物涂层球囊治疗原发血管病变中具有重要的临床意义。该文报道1例合并血小板减少及下肢静脉血栓的急性心肌梗死患者, 在多学科会诊评估调整抗凝、抗血小板药物后, 应用腔内影像指导成功行冠状动脉介入治疗, 术后随访3个月无出血及不良心血管事件发生。

关键词：血小板减少急性冠脉综合征血管成形术腔内影像药物涂层球囊

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Individualized vaginal applicator for stage IIb primary vaginal adenocarcinoma:A case report

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World Journal of Clinical Oncology 2024年第8期15卷 1102-1109页

作者： Saijilafu Yan-Jun Gu Ai-wu Huang Chang-Fen Xu Li-Wen Qian Hangzhou Lin'an Traditional Chinese Medicine Hospital Affiliated HospitalHangzhou City UniversityHangzhou 311300Zhejiang ProvinceChina Department of Radiation Oncology Sir Run Run Shaw HospitalHangzhou 310016Zhejiang ProvinceChina Department of the Gynecology and Obstetrics Hangzhou Lin'an Traditional Chinese Medicine HospitalAffiliated HospitalHangzhou City UniversityHangzhou 311300Zhejiang ProvinceChina

BACKGROUND Primary vaginal cancer is rare and most vaginal tumors are metastatic,often arising from adjacent gynecologic *** vaginal cancers are also more common among postmenopausal women and most of these are squamous cell carcinomas,with adenocarcinomas being relatively *** bleeding is the most common clinical manifestation of vaginal *** 70%of vaginal adenocarcinomas are stage I lesions at the time of diagnosis,for which radical surgery is ***,more advanced vaginal cancers are not amenable to radical surgical treatment and have poor clinical *** treatments modes are still being ***,we report a rare case of stage IIb primary vaginal adenocarcinoma for which an individually designed vaginal applicator for after-loading radiotherapy was used to achieve good tumor *** SUMMARY A 62-year-old woman presented to our clinic after 3 months of abnormal postmenopausal vaginal *** examination,computed tomography(CT),and positron emission tomography-CT showed a large mass(about 5 cm)on the anterior vaginal *** biopsy confirmed adenocarcinoma of vaginal *** three cycles of carboplatin plus paclitaxel chemotherapy,the lesion partially *** patient then received external irradiation of 45 gray(gy)in 25 fractions,which further reduced the vaginal lesion,followed by after-loading radiotherapy of 30 gy in 5 fractions with an individually designed vaginal *** months later,magnetic resonance imaging showed a slight thickening CONCLUSION Primary vaginal adenocarcinoma is rare,and prognosis is poor in most vaginal cancers of locally advanced stages,which cannot be treated with radical *** tumor control can be achieved with an individualized vaginal applicator that allows administration of a higher radical dose to the tumor area while protecting normal tissues.

关键词： Primary vaginal adenocarcinoma After-loading radiotherapy Vaginal applicator Tumor control Case report

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