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NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou ying Xiaoli Si Naijia xue yi liu Ran Zheng ying Chen Jiali Pu Baorong zhang Department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

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RGS22 maintains the physiological function of ependymal cells to prevent hydrocephalus

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Science China(Life Sciences) 2025年第2期68卷 441-453页

作者： xue pang Lin Gu Qiu-ying Han Jia-Qing Xing ming Zhao Shao-yi Huang Jun-Xi yi Jie pan Hao Hong Wen xue xue-Qing Zhou Zhi-Hui Su Xin-Ran zhang Li-ming Sun Shao-Zhen Jiang Dan luo Ling Chen Zheng-Jie Wang Yu Yu Tian Xia xue-min zhang Ai-Ling Li Tao Zhou Hong Cai Tao Li Nanhu Laboratory National Center of Biomedical AnalysisBeijing 100039China School of Basic Medical Sciences Fudan UniversityShanghai 200032China Department of Basic Medical Sciences School of MedicineTsinghua UniversityBeijing 100084China

Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid(CSF)flow by beating their motile cilia *** ependymal denudation or ciliary dysfunction causes ***,we report that the deficiency of regulator of Gprotein signaling 22(RGS22)results in severe congenital hydrocephalus in both mice and ***,RGS22 is specifically expressed in ependymal cells within the *** conditional knock-out mice,we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce ***,we show that Rgs22 deficiency leads to the ependymal denudation and impaired *** phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor(LPAR)signaling under Rgs22^(-/-)condition,as the LPAR blockade effectively alleviates hydrocephalus in Rgs22^(-/-)***,our findings unveil a previously unrecognized role of RGS22 in the central nervous system,and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus.

关键词： RGS22 hydrocephalus ependymal cells

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Modified Pulsatilla decoction alleviates 5-fluorouracil-induced intestinal mucositis by modulating the TLR4/MyD88/NF-κB pathway and gut microbiota

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World Journal of Gastroenterology 2025年第7期31卷 110-129页

作者： yi-Tong Qiu Xin-yi luo Ya-Feng Deng xue Zheng Jian-Guo Qiu Lin-Sheng zhang Xiao-Qi Huang xue-Bao Zheng Hai-Yang Huang School of Pharmaceutical Sciences Guangzhou University of Chinese MedicineGuangzhou 525000Guangdong ProvinceChina Druggability Research Team Dongguan Institute of Guangzhou University of Chinese MedicineDongguan 523808Guangdong ProvinceChina Institute of Traditional Chinese Medicine Dongguan Hospital of Traditional Chinese MedicineDongguan 523000Guangdong ProvinceChina

BACKGROUND Modified Pulsatilla decoction(PD),a PD with licorice and ejiao,is a classic Traditional Chinese Medicine formula with significant efficacy in treating intestinal mucositis(IM)induced by tumor ***,its specific molecular and biological mechanisms remain *** To investigate the therapeutic effect and mechanism of modified PD in *** This study used an IM mouse model established using 5-fluorouracil injections to investigate the effects of the modified PD(3,6,and 12 g/kg)in *** primary chemical components of the modified PD were identified using liquid chromatography-mass *** weight loss,diarrhea scores,intestinal length,histopathological scores,and inflammatory cytokine levels were measured to evaluate the effects of the modified PD in *** on the TLR4/MyD88/NF-κB pathway were evaluated using western blot *** intestinal microbiota was characterized using Illumina NovaSeq *** The results showed that modified PD significantly improved weight loss and diarrhea and shortened the intestines in IM ***,modified PD suppressed the TLR4/MyD88/NF-κB pathway and downregulated the expression of reactive oxygen species,lipopolysaccharides,and pro-inflammatory cytokines(IL-1β,TNF-α,IFN-γ,IL-6,IL-8,and IL-17),while increasing the expression of the anti-inflammatory cytokine ***,modified PD protected the intestinal mucosal barrier by increasing the expression of tight junction proteins(occludin-1,claudin-1,and ZO-1)and ***,16S rDNA sequencing revealed that modified PD improved intestinal *** Our research offers new insights into the potential mechanism of modified PD in alleviating IM and provides experimental evidence supporting its pharmaceutical application in clinical IM treatment.

关键词： Modified Pulsatilla decoction Intestinal mucositis Oxidative stress Gut microbiota,TLR4/MyD88/NF-κB pathway Inflammatory response

Study on the Radiation Synthesis Mechanism and the Electrochemical Property of Polyaniline

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Chinese Journal of Polymer Science 2025年第2期43卷 328-340页

作者： Shuo Yan Zi-Fang Guo Zhi-Qing Ge Bao-ying zhang Ya-Ru zhang yi-Shao Li Mo-Zhen Wang xue-Wu Ge State Key Laboratory of Precision and Intelligent Chemistry Department of Polymer Science and EngineeringUniversity of Science and Technology of ChinaHefei230026China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei230026China

As a highly promising conductive polymer material,the synthesis method,structure regulation,and performance improvement of polyaniline(panI)are hot research *** this work,the radiation-induced polymerization of aniline in HNO_(3)solution was successfully achieved at room temperature without the use of chemical *** the analysis of the radiation chemical reactions of inorganic acids and nitrate salt solutions,the characterization of the intermediate free radicals in the irradiated systems,and the influence of the pH of the solutions on the polymerization activity and product morphologies,the radiation-induced polymerization mechanism of aniline is discussed in detail and *** at a condition of[HNO_(3)]>[aniline],i.e.,pHpanI can be successfully obtained underγ-ray *** polymerization begins with the oxidation of aniline cations to aniline cation radicals by·NO_(3)generated by radiolysis reactions,and undergoes repeated three steps of monomer free radical recombination,deprotonation,and oxidation reaction of·NO_(3),thus forming a panI *** addition to the polymerization reaction,the aniline units are protonated and oxidized because of the strongly acidity and oxidation of the reaction system under γ-ray irradiation,which means that the molecular chain structure of the radiation-synthesized panI can be regulated by pH,nitrate concentration,and irradiation ***-synthesized panI has a moderate protonation and oxidation state,which can be used for the preparation of panI supercapacitors with better electrochemical properties than those prepared by chemical oxidation under the same *** work presents a new radiation-synthesis method and polymerization mechanism of panI,which not only expands the application of radiation technique in the field of polymer synthesis,but also provides a new idea for the structural regulation and electrochemical property optimization of panI.

关键词： Aniline Radiation-induced polymerization Polyaniline Electrochemical property

Docosahexaenoic acid， folic acid， and phosphatidylserine co-intervention alleviate cognitive impairment in D-galactose-induced aged mice

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Food Science and Human Wellness 2025年

作者： yingying Lin yi Cui yi xue Xiaoya lin Yuning zhang yiran Wang Lining Chen Zenghui Xia Huiyuan Guo Department of Nutrition and Health， China Agricultural University College of Food Science and Nutritional Engineering， China Agricultural University National Center of Technology Innovation for Dairy

Following the aging of the population， cognitive impairment is becoming a major public health issue. Research in recent years has highlighted the potential of docosahexaenoic acid (DHA)， folic acid (FA)， and phosphatidylserine (PS) to improve synaptic plasticity and reduce inflammatory response. However， whether a combined intervention is more effective than using these supplements alone remains unclear. To investigate this， we conducted an experiment on D-galactose-induced aging mice and found that the combining DHA， FA， and PS (DFP) improved spatial learning memory. Moreover， the DFP treatment restored cognitive performance by regulating antioxidant levels， inhibiting microglia activation， and reducing inflammation. The treatment also increased the expression of neurotrophic factors and synaptic-related proteins in the hippocampal region of the brain. Our findings suggest that the supplementation of DPF could be more beneficial than using DHA alone. This combined intervention could improve neurotrophic factor expression and decrease neuroinflammation in the brain of mice， thus reducing neuron damage and enhancing synaptic plasticity. In summary， our results indicate that the combined supplementation of DFP may improve cognition， and may be more effective than supplement with DHA alone.

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Lycium barbarum polysaccharide inhibits retinal neovascularization and inflammation in vitro and in vivo

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International Journal of Ophthalmology(English edition) 2025年第2期18卷 216-221页

作者： Bin Wu xue Wang Wei zhang Xin Wang Qi-Miao Wang Ya-Ju pang yi-Chun Kong Tianjin Eye Hospital Tianjin Key Lab of Ophthalmology and Visual ScienceTianjin Eye InstituteClinical College of Ophthalmology Tianjin Medical UniversityTianjin 300102China Department of Ophthalmology Tianjin Hospital of Integrated Traditional Chinese and Western MedicineTianjin 300100China

AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal ***:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N2),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP *** neovascularization was observed by fluorescein angiography and *** thickness was evaluated by Hematoxylin and eosin(HE)*** expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western ***-1βlevel in retina was analyzed using immunohistochemical ***:The increased area of neovascular clusters in OIR mice was significantly decreased by *** thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP *** with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control ***,IL-1βwas reduced in retinal sections treated with *** the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in ***:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt

关键词： Lycium barbarum polysaccharide neovascularization epidermal growth factor receptor retina

An evaluation model and its application of low-pressure abrasive air jet slitting hard rock

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Meitan xuebao/Journal of the China Coal Society 2025年第1期50卷 349-359页

作者： Wei, Jianping Cai, Yubo zhang, Tiegang xue, yi Ji, Songtao Chen, Changjiang zhang, Huidong liu, Yong State Key Laboratory Cultivation Base for Gas Geology and Gas Control Henan Polytechnic University Jiaozuo454000 China State Collaborative Innovation Center of Coal Work Safety and Clean-efficiency Utilization Jiaozuo454000 China School of Civil Engineering and Architecture Xi’an University of Technology Xi’an710048 China Key Laboratory of Western mines and Hazard Prevention of ministry of Education Xi’an University of Science and Technology Xi’an710054 China

Low-pressure abrasive air jet technology is one of the most promising methods for addressing the issues of low efficiency and significant tool wear in hard-rock drilling, owing to its strong rock-breaking capability and low energy consumption. However, the application of this technology faces challenges due to the reliance on single evaluation indices (e.g., slit depth, width, volume), which lack universality and generality, making it difficult to determine the optimal slit parameters under varying working conditions. This limitation significantly hampers the effectiveness of abrasive jet technology. To address this issue, proposes an evaluation model that integrates the quantitative relationships among slit parameters such as depth,width, and volume. A jet slit morphology distribution equation is derived through three-dimensional reconstruction and homogenization of rock slit morphology. The ratio of the mean area (A) of the slit morphology curve to the distribution function parameter (a1) is defined as the characteristic width of the slit, denoted as b, and the ratio of b to a1 is defined as the width-to-height ratio P. The effectiveness of the slit is evaluated using P, leading to the following conclusions: when P≤0.5, a narrower and deeper slit is formed;when P > 0.5, a wider and shallower slit is produced. By using P to characterize the slit effect under different parameter conditions, it is determined that when a deeper slit is required, the jet impact target distance should be maintained at 40 mm, the abrasive grain size should range between 60 and 90 mesh (0.16～0.25 mm), the abrasive hardness should exceed 7.0 on the Mohs scale, the mass flow rate of the abrasive should be between 16 g/s and 32 g/s, and an impact angle of 60° should be used. For obtaining a wide and shallow slit, the abrasive grain size should exceed 90 mesh (0.16 mm), the Mohs hardness should be less than 7.0, the abrasive mass flow rate should be lower than 8 g/s, the jet impact angle shou

关键词： Slitting

Effect of heat treatment on microstructure and mechanical properties of a novel Al-Zn-Mg-Cu alloy

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China Foundry 2025年

作者： Yan-mei Yang Xin-chen Tang Ye-fei Li xue-wei Fang Da-wei yi Zhi-yun zhang Qiao-ling Zheng Zhi-xi Wang Guo-yu zhang Su zhang Hao Cheng Yang He yi-bo liu Zi-han Wu Ya-nan Chen yi-min Gao State Key Laboratory for Mechanical Behavior of Materials Xi'an Jiaotong University Xi'an Aerospace Precision Electromechanical Institute

Effects of solution and aging treatment on the microstructure and mechanical properties of a novel Al-Zn-Mg-Cu alloy by microalloying rare elements Sc and Er were studied. The results show that solution time has a visible influence on the microstructure and mechanical properties of the alloy. Specifically, as the solution time increases, the area fraction of the residual phase in the alloy decreases, and the shape of the grain becomes more spheroidal and coarser, leading to a decrease in hardness. This is attributed to the dissolution of strengthening phases during the solution treatment, which weakens the solid solution strengthening *** single-stage aging treatment shows an initial increase in strength and hardness of the alloy, followed by a decrease as the aging time is extended, until a steady state is achieved. The optimal single-aging conditions are found to be at 120 ℃ for 24 h, where the alloy exhibits an excellent combination of high strength and good ductility, with an ultimate tensile strength(UTS) of 523 MPa, yield strength(YS) of 482 MPa, and elongation(El)of 1.75%, respectively. Compared to single-stage aging, double-stage aging(120 ℃ for 24 h and then 150 ℃ for 52 h) significantly increases the elongation of the alloy(4.17%), but the UTS reduces to 465.29 MPa, and YS reduces to 410.64 MPa. Transmission electron microscopy(TEM) observations disclose that the grain size, the distribution spacing of precipitates along the grain boundary, and the width of the precipitation-free zone(PFZ) all undergo augmentation as the duration of the second stage aging process elongates.

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The GECAM ground search system for gamma-ray transients

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Science China(Physics,Mechanics & Astronomy) 2025年第3期68卷 161-174页

作者： Ce Cai Yan-Qiu zhang Shao-Lin Xiong Ping Wang Jian-Hui Li Xiao-Bo Li Cheng-Kui Li Yue Huang Shi-Jie Zheng Li-ming Song Shuo Xiao Qi-Bin yi yi Zhao Sheng-lun Xie Rui Qiao Yan-Qi Du Zhi-Wei Guo Wang-Chen xue Chao Zheng Jia-Cong liu Chen-Wei Wang Wen-Jun Tan Yue Wang Jin-Peng zhang Chao-Yang Li Guo-ying Zhao Xiao-Yun Zhao Xiao-lu zhang Zhen zhang Wen-Xi Peng Xiang Ma Jing-Yan Shi Dong-Ya Guo Jin Wang Xin-Qiao Li Xiang-Yang Wen Zheng-Hua An Fan zhang College of Physics and Hebei Key Laboratory of Photophysics Research and Application Hebei Normal UniversityShijiazhuang050024China Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing100049China University of Chinese Academy of Sciences Beijing100049China School of Physics and Electronic Science Guizhou Normal UniversityGuiyang550001China Guizhou Provincial Key Laboratory of Radio Astronomy and Data Processing Guizhou Normal UniversityGuiyang550001China School of Physics and Optoelectronics Xiangtan UniversityXiangtan411105China School of Computer and Information Dezhou UniversityDezhou253023China Institute of Astrophysics Central China Normal UniversityWuhan430079China

In the era of time-domain,multi-messenger astronomy,the detection of transient events on the high-energy electromagnetic sky has become more important than *** gravitational wave high-energy electromagnetic counterpart all-sky monitor(GECAM)is a dedicated mission to monitor gamma-ray transients,launched in December,2020.A real-time on-board trigger and location software,using the traditional signal-to-noise ratio(SNR)method for blind search,is constrained to relatively bright signals due to the limitations in on-board computing resources and the need for real-time *** this work,we developed a ground-based pipeline for GECAM to search for various transients,especially for weak bursts missed by on-board *** pipeline includes both automatic and manual mode,offering options for blind search and targeted *** targeted search is specifically designed to search for interesting weak bursts,such as gravitational wave-associated gamma-ray bursts(GRBs).From the ground search of the data in the first year,GECAM has been triggered by 54 GRBs and other transients,including soft gamma-ray repeaters,X-ray binaries,solar flares,terrestrial gamma-ray *** report the properties of each type of triggers,such as trigger time and light *** this search pipeline and assuming a soft Band spectrum,the GRB detection sensitivity of GECAM is increased to about 1.1×10^(-8)erg cm^(-2)s^(-1)(10-1000 ke V,burst duration of 20 s).These results demonstrate that the GECAM ground search system(both blind search and targeted search)is a versatile pipeline to recover true astrophysical signals which were too weak to be found in the on-board search.

关键词： gamma-ray sources gravitational waves data analysis gamma-ray telescopes

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