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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng Zhou Kaimei Lu bin Fang Lijuan wang Lina Huang Zifeng Xu Department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original Diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

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miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-ting Sun Li-ting wang Xia Wu Ling-Jie Zhu Xiao-Jia Yang Qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei Huang Jiayi Wen Xin Xiong ting Xu Qi wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao Key Laboratory of Endemic and Ethnic Diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou Center for Disease Control and Prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

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Deciphering the role of mtH2O2 in hepatic ischemia-reperfusion injury mechanisms with low-background super-resolution fluorogenic probe

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Science China Chemistry 2025年第01期 297-307页

作者： bin Fang Limin wang Haoqin Li Jiaxin Zhang Yang Ding Pan Pan Li Bo Peng Hua Bai Lin Li Frontiers Science Center for Flexible Electronics Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials &Engineering Northwestern Polytechnical University Institute of Flexible Electronics (IFE Future Technologies) Xiamen University

Hepatic ischemia-reperfusion injury（HIRI） is characterized by mitochondrial dysfunction and oxidative stress. Monitoring mitochondrial hydrogen peroxide（mtH2O2） levels in real-time through super-resolution imaging is crucial for elucidating its distribution in live cells and its mechanism of action during HIRI. However, low-background fluorogenic probes have been overlooked in the context of super-resolution imaging. In this study, we developed a low-background fluorogenic probe（MitoWG） with the potential for super-resolution morphology-correlated mitochondrial identification to track the fluctuates of mtH2O2in HIRI. Activation of the desirable fluorescence properties of the probe by mtH2O2was confirmed using structural illumination microscopy（SIM）, enabling high-quality mitochondrial imaging with exceptional specificity and *** in mtH2O2levels were successfully observed in both cellular and rat models of HIRI. Furthermore, we associated the decline in mitochondrial redox homeostasis with accelerated mtH2O2production during HIRI, which triggered mitophagy deficiency and led to cell death. In conclusion, Mito-WG possesses excellent photophysical and low-background properties for SIM imaging, making it a promising tool for mtH2O2tracking in HIRI research and clinical diagnosis.

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Direct Photolithography of WO_x Nanoparticles for High-Resolution Non-Emissive Displays

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NANO-MICRO LETTERS 2025年第1期17卷 1-13页

作者： Gu, Chang Yang, Guojian wang, Wenxuan Shi, Aiyan Fang, Wenjuan Qian, Lei Hu, Xiaofei Zhang, ting Xiang, Chaoyu Zhang, Yu-Mo Chinese Acad Sci Ningbo Inst Mat Technol & Engn Lab Optoelect Informat Technol & Devices Ningbo 315201 Peoples R China Qianwan Inst CNITECH Hangzhou Bay Lab Adv Nanooptoelectron Mat & Device Ningbo 315336 Peoples R China Zhejiang Univ Innovat Ctr Yangtze River Delta Smart Mat Architecture Res Lab Jiaxing 314100 Peoples R China Univ Sci & Technol China Hefei 230026 Peoples R China Jilin Univ Coll Chem State Key Lab Supramol Struct & Mat Changchun 130012 Peoples R China

High-resolution non-emissive displays based on electrochromic tungsten oxides (WOx) are crucial for future near-eye virtual/augmented reality interactions, given their impressive attributes such as high environmental stability, ideal outdoor readability, and low energy consumption. However, the limited intrinsic structure of inorganic materials has presented a significant challenge in achieving precise patterning/pixelation at the micron scale. Here, we successfully developed the direct photolithography for WOx nanoparticles based on in situ photo-induced ligand exchange. This strategy enabled us to achieve ultra-high resolution efficiently (line width m, the best resolution for reported inorganic electrochromic materials). Additionally, the resulting device exhibited impressive electrochromic performance, such as fast response ( 3600 cycles), as well as promising applications in electronic logos, pixelated displays, flexible electronics, etc. The success and advancements presented here are expected to inspire and accelerate research and development (R&D) in high-resolution non-emissive displays and other ultra-fine micro-electronics.

关键词： Electrochromic Direct photolithography WOx nanoparticles In situ photo-induced ligand exchange High-resolution displays

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Effect of beam current on microstructures and mechanical properties of joints of TZM/30CrMnSiA by electron beam welding

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Chinese Journal of Aeronautics 2021年第8期34卷 122-130页

作者： ting wang bin YU Yifan wang Siyuan JIANG State Key Laboratory of Advanced Welding and Joining Harbin Institute of Technology at WeihaiWeihai 264209China Shandong Provincial Key Laboratory of Special Welding Technology Harbin Institute of Technology at WeihaiWeihai 264209China

Electron beam welding experiments of TZM alloy and 30CrMnSiA steel butt joints were carried out with different beam *** and chemical compositions of typical zones were analyzed by optical microscopy,scanning electron microscopy and X-ray *** mechanical properties of the joints were evaluated by tensile strength ***,nanoindentation tests were carried out to compare the brittleness of the reaction layer and other typical *** results illustrated that the reaction layer at the interface between fusion zone(FZ)and TZM alloy was the weak position of the joint,which was divided into Fe2Mo layer and a mixture layer of Fe2Mo and a-Fe *** the beam current increased,the thickness of the Fe2Mo layer decreased,which resulted in the increasing of the tensile strength of the *** the beam current exceeded 24 m A,the formation of the joint was poor with a low tensile *** the beam current was 24 mA,the joint presented the highest strength of 191.3 MPa and the joint fractured along the Fe2Mo layer near the TZM alloy side with a brittle fracture mode.

关键词： 30CrMnSiA Electron beam welding Mechanical properties Microstructure TZM alloy

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期 308-316页

作者： Sili wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

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Targeting epigenetic regulators to overcome drug resistance in cancers

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1070-1093页

作者： Nan wang ting Ma bin Yu Institute of Drug Discovery&Development School of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China

Drug resistance is mainly responsible for cancer recurrence and poor *** regulation is a heritable change in gene expressions independent of nucleotide sequence *** the common epigenetic regulation mechanisms,DNA methylation,histone modification,and non-coding RNA regulation have been well *** evidence has shown that aberrant epigenetic regulations contribute to tumor ***,targeting epigenetic regulators represents an effective strategy to reverse drug *** this review,we mainly summarize the roles of epigenetic regulation in tumor *** addition,as the essential factors for epigenetic modifications,histone demethylases mediate the histone or genomic DNA ***,we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family,the Jumonji C-domain-containing demethylase family,and the histone arginine demethylase family,and fully discuss their regulatory mechanisms related to cancer drug *** addition,therapeutic strategies,including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance,are also described.

关键词： epigenetic drug overcome

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氟诺哌齐结构和性质的密度泛函理论研究

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原子与分子物理学报 2025年第2期42卷 41-48页

作者：孙婷婷王德堂徐州工业职业技术学院化学工程学院徐州221140

氟诺哌齐是一种新型的抗阿尔茨海默病临床候选药物,目前尚处于临床试验阶段;对氟诺哌齐进行密度泛函理论研究,有助于揭示其分子的性质和功能.在B3LYP/6-311+G(d,p)基组水平上,采用密度泛函理论(DFT)的方法优化氟诺哌齐的分子结构;在相... 详细信息

氟诺哌齐是一种新型的抗阿尔茨海默病临床候选药物,目前尚处于临床试验阶段;对氟诺哌齐进行密度泛函理论研究,有助于揭示其分子的性质和功能.在B3LYP/6-311+G(d,p)基组水平上,采用密度泛函理论(DFT)的方法优化氟诺哌齐的分子结构;在相同基组水平下经过谐振频率分析,证实了12种分子构象的稳定结构,并确定了优势构型为DC20-1.根据Marcus理论,对其重组能进行模拟计算,得出氟诺哌齐分子不具备运输性质.通过前线轨道(FMO)分析,发现氟诺哌齐分子具有一定的电子跃迁能力和分子内反应活性,活性反应位点为C15、O28、C23和O26.根据红外光谱、紫外-可见吸收光谱模拟计算结果,对谱图数据进行了讨论分析,研究结果可作为氟诺哌齐表征和鉴别的参考依据.

关键词：氟诺哌齐密度泛函(DFT) 重组能前线轨道(FMO) 红外光谱(IR) 紫外-可见吸收光谱(UV-Vis)

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