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Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

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Neural Regeneration Research 2025年第2期20卷 354-365页

作者： li Xu Huiming Xu Changyong Tang Department of Neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor *** date,no effective treatment exists as the exact causative mechanism remains ***,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic *** most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets *** experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum *** this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model *** addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

关键词： aquaporin-4 experimental model neuromyelitis optica spectrum disorder pathogenesis

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Local magnetic moment oscillation around an Anderson impurity on graphene

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 192-201页

作者： Shuai li Zhen Ma Jin-Hua Gao School of Science Hebei University of Science and Technology School of Electronics and Information Zhengzhou University of Light Industry School of Physics and Wuhan National High Magnetic Field Center Huazhong University of Science and Technology

We theoretically investigate the spin resolved Friedel oscillation （FO） and quasiparticle interference （QPI） in graphene induced by an Anderson *** the impurity becomes magnetic,the resulted FO becomes spin dependent,which gives rise to a local magnetic moment oscillation with an envelop decaying as r-2in real space in the doping ***,at half filling,the electron density and local magnetic moment will not oscillate but decay as *** spin resolved FO has both sublattice and spin ***,the local magnetic moment decay at half filling only occurs at one sublattice of graphene,which is quite like the phenomenon observed in the STM experiment (***ález-Herrero et al.,Science 352,437 （2016）).We further give an analytic formula about such spin dependent FO based on the stationary phase ***,we study the interference of quasiparticles around the magnetic impurity by calculating the spin dependent Fourier-transformed local density of states （FT-LDOS）.Our work gives a comprehensive understanding about the local magnetic moment oscillation around an Anderson impurity on graphene.

关键词： Friedel oscillation local magnetic moment graphene Anderson impurity

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Inhibition of the NLRP3 inflammasome attenuates spiral ganglion neuron degeneration in aminoglycoside-induced hearing loss

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Neural Regeneration Research 2025年第10期20卷 3025-3039页

作者： Jia Fang Zhuangzhuang li Pengjun Wang Xiaoxu Zhang Song Mao Yini li Dongzhen Yu Xiaoyan li Yazhi Xing Haibo Shi Shankai Yin Department of Otolaryngology Head and Neck Surgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineOtolaryngology Institute of Shanghai Jiao Tong UniversityShanghai Key Laboratory of Sleep Disordered BreathingShanghaiChina Department of Otorhinolaryngology-Head and Neck Surgery Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial ***,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct *** addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon *** investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with *** found that the mice exhibited auditory deficits following the acute loss of outer hair *** ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over *** profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 *** of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory *** intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury *** findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron *** of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.

关键词： degeneration hearing loss macrophages Mcc950 neuroinflammation NLRP3 inflammasome ototoxicity pyroptosis sensorineural hearing loss spiral ganglion neuron

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Identification of a dual functional betulinic acid analog for the treatment of osteoarthritis by phenotypic screening

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Science China life Sciences 2025年第1期 300-302页

作者： Ze-Min lin Mai Xiang Wen-Hui Wei Shu-Hui Fan li Chen Jie Wang Xiao-Qian Yang chun-Hao Yang Shi-Jun He Jian-Ping Zuo Laboratory of Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy University of Chinese Academy of Sciences School of Pharmacy Nanjing University of Chinese Medicine State Key Laboratory of Drug Research Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of Sciences Innovation Research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Experiment Center for Science and Technology Shanghai University of Traditional Chinese Medicine

Dear Editor, Phenotypic drug discovery, which observes compound effects on physiology,has given way to targeting specific molecules, but has revived by using modern methods to find drugs based on therapeutic outcomes in disease models(Vincent et al., 2022). Osteoarthritis(OA) is a prevalent chronic joint disorder, primarily affecting knee joints, with osteoclast activation due to low-grade inflammation resulting in increased bone resorption and structural changes in the joint(Katz et al.,2021).

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Enhanced Phase Transition in Poly(ethylene glycol) Grafted Butene-1 Copolymers

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Chinese Journal of Polymer Science 2023年第3期41卷 414-421,I0008页

作者： Ya-Hui Lou Wei li chun-jing Qv Zhe Ma Tianjin Key Laboratory of Composite and Functional Materials and School of Materials Science and EngineeringTianjin UniversityTianjin 300072China

In the present work,a series of poly(ethylene glycol) grafted polybutene-1 copolymers(PB-g-PEG) were designed and successfully synthesized with reaction intermediate method,of which the branch densities and length could be tuned *** branch density varied from 0.39 mol% to 1.23 mol% and the branch length was tuned by employing PEG number-averaged molecular weight(Mn) from 350 Da to 750 Da and 1000 *** non-isothermal crystallization and phase transition behaviors of these butene-1 copolymers with varying branches were systematically explored by differential scanning *** results first showed that compared with the linear polybutene-1 homopolymer,presence of steric 4-[4-(trimethylsilylalkynyl)-phenyl]-1-butene(TMS) groups suppressed crystallization and phase transition of ***,the introduction of long poly(ethylene glycol)(PEG) branches with M_(n)=350-1000 Da not only elevated the peak temperature of the non-isothermal crystallization but also enhanced the Ⅱ-Ⅰ phase transition,with respect to copolymers with TMS ***,the quantitative correlations between phase transition kinetics with the branch parameters(density and length) were *** was found that the phase transition presents a non-monotonic trend with increasing branch density and branch *** this case,the optimal branch density and length obtained were 0.77 mol% and 750 Da,*** the small angle X-ray scattering and transmission electron microscopy,a direct correlation between the phase transition kinetics and the long periodicity of separated phase was obtained,which may be due to the increased internal stress and facilitated stress transport.

关键词： Polybutene-1 copolymer Crystallization kinetics Phase transition Phase separation

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Memory Effect of Crystallization in 1-Butene/α-olefin Copolymers

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Chinese Journal of Polymer Science 2022年第6期40卷 576-583页

作者： chun-jing Qv Wei li Rui-Jun Zhao Zhe Ma Tianjin Key Laboratory of Composite and Functional Materials and School of Materials Science and EngineeringTianjin UniversityTianjin 300072China

The macromolecular architecture is the crucial factor in determining the arrangement of the ordering structures,which,because of the multiscale feature,may exhibit distinct melting behaviors and induce the so-called memory effect to affect the following *** present,the correlation between the occurrence of memory effect and the intrinsic molecular structure is still far from the comprehensive *** this work,four kinds of 1-butene/α-olefin random copolymers were designed and synthesized using the(pyridyl-amino)hafnium catalyst to introduce the different *** branch length was precisely controlled by the specific α-olefin comonomers,which include 1-hexene,1-decene,1-tetradecene,and 1-octadecene,while the branch density was tuned by the *** expected,the incorporation of α-olefin co-units to poly(1-butene)backbone decreases the non-isothermal crystallization kinetics and the degree of *** interestingly,the resulting linear branch can induce the occurrence of memory effect and the threshold concentration of co-units(i.e.,branch density)decreases with increasing the branch *** on the results of these 1-butene/α-olefin copolymers with designable branches,a direct correlation with the occurrence of memory effect and the fraction of amorphous region was established,which quantitatively indicates the degree of local segregation of the crystallized poly(1-butene)sequences by theα-olefin co-units.

关键词： Memory effect 1-Butene/α-olefin copolymer linear branch Crystallinity

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[Recent progress in mass spectrometry imaging using nanospray desorption electrospray ionization]

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Se pu = Chinese journal of chromatography 2025年第1期43卷 43-49页

作者： jing-Bo Wang Xiao-Lan li Rui-Xia Fan Ping Lü Rui-Chuan Yin West China School of Pharmacy Sichuan University Chengdu 610041 China.

Ambient mass spectrometry imaging (MSI) enables hundreds of analytes in tissue sections to be directly mapped at atmospheric pressure with minimal sample preparation. This field is currently experiencing rapid growth, with numerous reported ambient ionization techniques resulting in a "hundred flowers bloom" situation. Nanospray desorption electrospray ionization (nano-DESI), developed by the Laskin group in 2010, is a widely used liquid-extraction-based ambient ionization technique that was first used for mass spectrometry imaging of tissue in 2012. The nano-DESI probe comprises a primary capillary and a nanospray capillary, with the latter efficiently transferring analyte-containing droplets via a tiny liquid bridge formed between the probe and sample surface, thereby enabling nanoelectrospray ionization (nano-ESI) in front of the inlet of a mass spectrometer. The advantages of nano-DESI MSI include minimal sample preparation, high spatial resolution, and high sensitivity. These features are well-suited for imaging various sample types, including frozen tissue sections, microbial communities, and environmental samples. A PubMed-database search using the "nano-DESI" keyword revealed 72 related articles in the 2010-2024 period, with 34 of them published between 2021 and 2024, which indicates that nano-DESI has rapidly developed as an ambient ionization technique over recent years. Herein, we briefly introduce key nano-DESI-MSI research progress reported in the past three years with the aim of better understanding and facilitating the use of this technology. We first discuss advances in ion-source development. Since no commercial nano-DESI source exists, designing and constructing ion sources remain technical challenges that limit its development. Nano-DESI has been successfully coupled with various types of mass spectrometer, including LTQ Orbitrap, quadrupole-Orbitrap (Q Exactive), 6560 IM QTOF, timsTOF Pro2, triple quadrupole, and FTICR. These couplings have signi

关键词： ambient mass spectrometry imaging nanospray desorption electrospray ionization spatial proteomics structural characterization of lipid

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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

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Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang chunxiao Wei Panpan Zhao Yongchun Wang Mingxi li li Sun Department of Neurology and Neuroscience Center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment Center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

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Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu linxi li Yunxiang Ji Yezhong Wang Yingjia li Yongyi Ye Department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s *** perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory ***,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly *** this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s *** suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in ***,the neurotoxic effects were mitigated,which alleviated neuronal ***,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic *** further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α***,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关键词： metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases neuroinflammation oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry

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The protective effect of zeaxanthin on human limbal and conjunctival epithelial cells against UV-induced cell death and oxidative stress

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International Journal of Ophthalmology(English edition) 2019年第3期12卷 369-374页

作者： Yue Huang chun Shi jing li Department of Ophthalmology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Department of Ophthalmology Xinhua Hospital Chong Ming Branch Shanghai Jiao Tong University School of Medicine Department of Ophthalmology Jiangwan Hospital of Hongkou District

AIM: To explore the protective effect of zeaxanthin on human limbal and conjunctival epithelial cells against UVradiation and excessive oxidative ***: Human limbal and conjunctival epithelial cells were isolated from cadaver and cultured in vitro. They were challenged with UVB radiation and H2 O2 with and without zeaxanthin pretreatment. Cell viability, p38 and c-JUN NH(2)-terminal kinase(JNK) phosphorylation, IL-6, IL-8 and MCP-1 secretion and malondialdehyde(MDA) content were ***: Zeaxanthin had no measurable cytotoxicity on limbal or conjunctival epithelial cells when used at concentrations of 5 μg/mL and below. At 30 mJ/cm2 UVB, the pretreatment of zeaxanthin increased the percentage of live cells from 50% to 69%(P=0.01) and from 66% to 75%(P=0.05) for limbal and conjunctival epithelial cells, respectively. The concentrations of IL-6, IL-8 and MCP-1 in the culture medium reduced to 66%(for IL-6 and MCP-1)and 56%(for IL-8) of the levels without zeaxanthin. This was accompanied by reduced p38 and JNK protein phosphorylation. Pretreatment of zeaxanthin also reduced intracellular MDA content caused by H2 O2 stimulation from 0.86 μmol/L to 0.52 μmol/L(P=0.02) in limbal epithelial cells and from 0.96 μmol/L to 0.56 μmol/L in conjunctival epithelial cells(P=0.03). However, zeaxanthin did nothave significant effect on H2 O2-induced cell death in limbal or conjunctival epithelial ***: Zeaxanthin is an effective reagent in reducing the detrimental effect of UV-radiation and oxidative stress on ocular surface epithelial cells.

关键词： zeaxanthin UV-radiation oxidative stress malondialdehyde limbal epithelial cells conjunctival epithelial cells

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