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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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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan zheng Qingming Lin Yan You zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial key Laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

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Neural Regeneration Research 2025年第6期20卷 1582-1598页

作者： Yanxi Li Jing Xue Yuejia Ma ke Ye Xue Zhao Fangliang Ge Feifei zheng Lulu Liu Xu Gao Dayong Wang Qing Xia Department of Biochemistry and Molecular Biology College of Basic Medical SciencesHarbin Medical UniversityHarbinHeilongjiang ProvinceChina College of Basic Medical Sciences Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Basic Medical Institute Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina key Laboratory of Heilongjiang Province for Genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be a

关键词： Alzheimer's disease cell self-renewal central nervous system memory microglia nerve regeneration neurodegenerative diseases neurogenesis RNA methylation

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Primary parenchymal squamous cell carcinoma of the kidney:A case report

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World Journal of Clinical Cases 2025年第4期13卷 34-40页

作者： zhi-Hui zheng Bo Shao Chao-Min Xu ke Wang Jia-Zhu Wen Li-Kang Luo Jia-Cheng Guan Department of Ultrasound The Second People’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina Department of Radiology Shulan(Quzhou)HospitalQuzhou 324000Zhejiang ProvinceChina Department of Radiology The Second People’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina Department of Pathology The Second people’s Hospital of QuzhouQuzhou 324000Zhejiang ProvinceChina

BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases *** SUMMARY This study reports a 51-year-old man with primary SCC of the renal *** patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross *** antigen(SCCA)levels were elevated,and imaging revealed a renal mass with associated *** patient underwent laparoscopic unilateral nephrectomy and lymph node *** pathology confirmed highly differentiated SCC with necrosis in the right renal parenchyma,with negative renal pelvis and *** pathological stage was *** months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena *** patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease *** We report a case of primary SCC of the renal parenchyma,a rare renal *** clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis *** to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum SCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.

关键词： Renal tumor Renal parenchyma Squamous cell carcinoma Renal calculi Computed tomography Case report

Activatable chemiluminescence probe based on four-arm PEGconjugated-pyropheophorbide-a for in vivo autofluorescence-free imaging of peroxynitrite

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Science China Chemistry 2025年

作者： Jianmei ke Lei Ding Ronggui Lian Cheng zheng Wenjun Li Aixian zheng Yupeng Sun Ming Wu Yongyi Zeng Xiaolong Liu Maochun Hong Xiaolong Zhang The United Innovation of Mengchao Hepatobiliary Technology key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Ganjiang Innovation Academy Chinese Academy of Sciences School of Rare Earths University of Science and Technology of China College of Chemistry Fuzhou University State key Laboratory of Structure Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences

Peroxynitrite（ONOO-） is a highly reactive nitrogen species that plays pivotal roles in cell signal transduction and physiological or pathological progresses. However, commonly used ONOO-optical imaging probes are still hampered by high background/autofluorescence（fluorescence probe）, short emission wavelength, or poor selectivity in the case of chemiluminescence. Herein,we report a facile method to prepare an activatable chemiluminescence probe（PPA-PEG） with good biocompatibility and functionality for in vivo autofluorescence-free imaging of ONOO-. The PPA-PEG consists of pyropheophorbide-a（PPA）, a typical deep red photosensitizer that acts as both the recognition and signaling element, and 4-arm poly（ethylene glycol）(4-arm PEG), which improves the biosafety and water solubility of probe. These components can self-assemble into nanoparticles（namely PPA-PEG nanoprobe） in aqueous solution. The PPA-PEG nanoprobe showed an ultra-low chemiluminescence signal before interacting with ONOO-, but exhibited good selectivity, high sensitivity and a fast response toward ONOO-. The PPAPEG was successfully applied to image cellular ONOO-changes, as well as the endogenous ONOO-changes in inflammation models and subcutaneous or orthotopic hepatocellular carcinoma（HCC） tumors models in living mice. In vitro and in vivo studies verified the good detection and imaging capabilities of PPA-PEG for peroxynitrite, demonstrating suitable tissue penetration and a high signal-to-background ratio（SBR）. Thus, our nanoprobe can serve as a valuable activatable chemiluminescence imaging tool for studying important peroxynitrite-related chemical and biological applications.

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Potassium ions and cyano group modified g-C3N4 for effective generation of H2O2 through two-electron oxygen reduction

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Science China Chemistry 2025年第1期 192-200页

作者： Dongying Wang Shulan pu Yongmin Chen ke Lei Yujie Duan Linjiao Mao Xuhui Zeng Xi Luo Yuntao Zhang Yuqin Dong Jin Zhong Zhang Yan Sun School of Mechanical Engineering Chengdu University Department of Chemistry and Biochemistry University of California

Potassium ions （K+） doped graphitic carbon nitride （g-C3N4） was prepared by a thermal etching method using potassium hydroxide （KOH） as an ion *** transform infrared spectroscopy （FTIR） and X-ray photoelectron spectroscopy （XPS）results showed that the generation of the cyano group was detected while introducing K+.Under simulated sunlight irradiation,the sample with a K+doping amount of 10%showed the highest hydrogen peroxide （H2O2） generation rate of2,140.2μmol *** apparent quantum yield （AQY） at 400 nm and the solar-to-chemical conversion （SCC） are 4.35%and1.23%,respectively.K+acted as a bridge between g-C3N4layers,which enhanced charge transfer ***,the cyano group enhanced the adsorption capacity of protons （H+） and promoted the yield of *** catalyst exhibited excellent photocatalytic stability based on four-cycle *** addition,a mechanism study showed that superoxide radicals （·O2-）were the most important active species in the reaction *** production of H2O2was achieved through consecutive single-electron *** study deepens the understanding of the oxygen reduction reaction process and opens up a new venue for improving H2O2generation.

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Surface micro-arrays enhancing electromagnetic interference shielding of polydimethylsiloxane/multiwalled carbon nanotubes nanocomposites

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Nano Research 2025年第1期18卷 508-519页

作者： ke Jiang zhi Chen Ji Yu Chen zheng Shan Huang Ming Wang Chongqing key Laboratory of Soft-Matter Material Manufacturing School of Chemistry and Chemical EngineeringSouthwest UniversityChongqing 400715China School of Mechanics Civil Engineering and ArchitecturesNorthwestern Polytechnical UniversityXi’an 710072China Jieyang Branch of Chemistry and Chemical Engineering Guangdong Laboratory(Rongjiang Laboratory) Jieyang 515200China

Herein,the electromagnetic shielding performance of surface concave-convex(SC)and zig-zag micro-arrays was studied by using a simulation prediction and a three-dimensional(3D)printing custom ***,surface stripe concaveconvex(SSC)and surface cylindrical concave-convex(SCC)micro-arrays with or without zig-zag micro-arrays are designed,and their shielding performance is simulated in multi-bands(C-,X-band).The multiwalled carbon nanotubes/polydimethylsiloxane composites(MWCNT/PDMS)with different SC structures and different electrical conductivity are molded in acrylonitrile-butadiene-styrene copolymer(ABS)molds which are printed by a 3D *** results show that the electromagnetic interference shielding effectiveness(EMI SE)of the samples can be enhanced by constructing the SC micro-arrays with zig-zag micro-arrays,and improving with the increase of conductivity and *** addition,the shielding mechanism of the SC-MWCNT/PDMS composites is investigated and discussed by an electromagnetic simulation.

关键词： surface micro-arrays electrical properties electromagnetic interference(EMI)shielding three-dimensional(3D)printing

Double-temperature ratchet model and current reversal of coupled Brownian motors

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Frontiers of physics 2017年第6期12卷 43-52页

作者： Chen-pu Li Hong-Bin Chen zhi-gang zheng Department of Physics Beijing Normal University Beijing 100875 China College of Science Hebei University of ArchitectureZhangjiakou 075000 China Institute of Systems Science (ISS) Huaqiao University Xiamen 361021 China College of Information Science and Engineering Huaqiao University Xiamen 361021 China

On the basis of the transport features and experimental phenomena observed in studies of molecular motors, we propose a double-temperature ratchet model of coupled motors to reveal tile dynamical mechanism of cooperative transport of motors with two heads, where the interactions and asynchrony between two motor heads are taken into account. We investigate the collective unidirectional trans- port of coupled system and find that the direction of motion can be reversed under certain conditions. Reverse motion can be achieved by modulating the coupling strength, coupling free length, and asym- metric coefficient of the periodic potential, which is understood in terms of the effective potential theory. The dependence of the directed current on various parameters is studied systematically. Di- rected transport of coupled Brownian motors can be manipulated and optimized by adjusting the pulsation period or the phase shift of the pulsation temperature.

关键词： coupled Brownian motors ratchet model effective potential noise

Ratchet motion and current motors in pulsating reversal of coupled Brownian symmetric potentials

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Frontiers of physics 2017年第4期12卷 197-206页

作者： Chen-pu Li Hong-Bin Chen zhi-gang zheng Department of Physics Beijing Normal University Beijing 100875 China College of Science Hebei University of Architecture Zhangjiakou 075000 China Institute of Systems Science (ISS) Huaqiao University Xiamen 361021 China College of Information Science and Engineering Huaqiao University Xiamen 361021 China

In this study, we investigate the collective directed transport of coupled Brownian particles in spatially symmetric periodic potentials under time-periodic pulsating modulations. We find that the coupling between two particles can induce symmetry breaking and consequently collective directed motion. Moreover, the direction of motion can be reversed under certain conditions. The dependence of directed current on various parameters is systematically studied, reverse motion can be achieved by modulating the coupling free length and the phase shift of tile pulsating potential. The dynamical mechanism of these transport properties is understood in terms of the effective-potential theory and the space-time transformation invariance. The directed transport of coupled Brownian motors can be maniplflated and optimized by adjusting the coupling strength, pulsating frequency, or noise intensity.

关键词： coupled Brownian motors ratchet effective potential symmetric periodic potential noise