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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

Segmental hair analysis for flunitrazepam and 7-aminoflunitrazepam in users:a comparison to existing literature

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forensic sciences Research 2022年第2期7卷 299-307页

作者： Yue Zhuo Ping Xiang Jingjie Wu Xin Wang department of forensic medicine Guizhou Medical UniversityGuiyangChina department of forensic Toxicology Academy of Forensic ScienceShanghai Key Laboratory of Forensic MedicineShanghaiChina Institute of forensic medicine Guizhou Police CollegeGuiyangChina

The availability of more quantitative data on flunitrazepam(FLU)and 7-aminoflunitrazepam(7AF)would aid in obtaining a better understanding of the interpretation of FLU concentrations in human *** purpose of this study was to provide concentrations of FLU and 7AF in hair segments of 22 FLU *** data regarding hair concentrations of FLU and 7AF from various types of cases were also reviewed to give a comprehensive overview of the comparability of different *** to six 1 cm segments of scalp hair from 22 FLU users were analyzed by a liquid chromatography–tandem mass spectrometry(LC–MS/MS)*** and its metabolite were confirmed in the hair segments from all *** of FLU and 7AF in the segments ranged from 0.01–0.16 ng/mg(median of 0.03)and 0.01–0.34 ng/mg(median of 0.09),*** cases had FLU and 7AF distributions along the hair segments that were suggestive of repeated drug use.A summary of the published concentrations gives valuable data and can assist forensic investigators in their estimations of drug use history and patterns.

关键词： forensic sciences forensic toxicology segmental hair analysis flunitrazepam 7-aminoflunitrazepam liquid chromatography-tandem mass spectrometry

Regression analysis of squeezing-induced hybrid nanofluid flow in Darcy-Forchheimer porous medium

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 193-208页

作者： K.MUHAMMAD M.SARFRAZ department of Humanities and sciences School of Electrical Engineering and Computer Science National University of Sciences and Technology department of Mathematics Quaid-i-Azam University

This article presents a mathematical model addressing a scenario involving a hybrid nanofluid flow between two infinite parallel plates. One plate remains stationary, while the other moves downward at a squeezing velocity. The space between these plates contains a Darcy-Forchheimer porous medium. A mixture of water-based fluid with gold(Au) and silicon dioxide(Si O2) nanoparticles is formulated. In contrast to the conventional Fourier's heat flux equation, this study employs the Cattaneo-Christov heat flux equation. A uniform magnetic field is applied perpendicular to the flow direction, invoking magnetohydrodynamic(MHD) effects. Further, the model accounts for Joule heating, which is the heat generated when an electric current passes through the fluid. The problem is solved via NDSolve in MATHEMATICA. Numerical and statistical analyses are conducted to provide insights into the behavior of the nanomaterials between the parallel plates with respect to the flow, energy transport, and skin *** findings of this study have potential applications in enhancing cooling systems and optimizing thermal management strategies. It is observed that the squeezing motion generates additional pressure gradients within the fluid, which enhances the flow rate but reduces the frictional drag. Consequently, the fluid is pushed more vigorously between the plates, increasing the flow velocity. As the fluid experiences higher flow rates due to the increased squeezing effect, it spends less time in the region between the plates. The thermal relaxation, however, abruptly changes the temperature, leading to a decrease in the temperature fluctuations.

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Asymptotic false discovery control of the Benjamini-Hochberg procedure for pairwise comparisons

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science China Mathematics 2025年第1期 223-252页

作者： Weidong Liu Dennis Leung Qi-Man Shao School of Mathematical sciences Shanghai Jiao Tong University School of Mathematics and Statistics University of Melbourne department of Statistics and Data science SICMSouthern University of Science and Technology

In a one-way analysis-of-variance(ANOVA) model,the number of pairwise comparisons can become large even with a moderate number of *** by this,we consider a regime with a growing number of groups and prove that,when testing pairwise comparisons,the Benjamini-Hochberg(BH) procedure can asymptotically control false discoveries,despite the fact that the involved t-statistics do not exhibit the wellknown positive dependence structure required for exact false discovery rate(FDR) *** Tukey's perspective that the difference between the means of any two groups cannot be exactly zero,our main result provides control over the directional false discovery rate and directional false discovery proportion.A key technical contribution of our work is demonstrating that the dependence among the t-statistics is sufficiently weak to establish the convergence result typically required for asymptotic FDR *** analysis does not rely on conventional assumptions such as normality,variance homogeneity,or a balanced design,thereby offering a theoretical foundation for applications in more general settings.

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Estimation of the age of human semen stains by attenuated total reflection Fourier transform infrared spectroscopy:a preliminary study

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forensic sciences Research 2020年第2期5卷 119-125页

作者： Shuai Zha Xin Wei Ruoxi Fang Qi Wang Hancheng Lin Kai Zhang Haohui Zhang Ruina Liu Zhouru Li Ping Huang Zhenyuan Wang department of forensic Pathology Xi’an Jiaotong University School of MedicineXi’anChina department of forensic medicine Chongqing Medical UniversityChongqingChina department of forensic medicine Xuzhou Medical UniversityXuzhouChina department of forensic Pathology Academy of Forensic ScienceShanghaiChina

Semen stain is one of the most important biological evidence at sexual crime *** estimation of human semen stains plays an important role in forensic work,and it is rarely studied due to lack of well-established *** this study,the technique called attenuated total reflection Fourier transform infrared spectroscopy(ATR-FTIR)coupled with advanced chemometric methods was employed to determine the age of semen stains on three different substrates:glass slides,tissues and fabric made of regenerated cellulose fibres up to 6 *** least squares regression(PLSR)was used in conjunction with spectral analysis for age estimation,and the results generated high R2 values(cross-validation:0.81,external validation:0.74)but a narrow margin of error for root mean square error(RMSE)(RMSE of cross-validation:0.77 d,RMSE of prediction:1.02 d).Additionally,our results indicated the robustness of PLSR model was not weaken by the influence of different substrates in this *** results indicate that ATR-FTIR,combined with chemometric methods,shows great potential as a convenient and efficient tool for age estimation of semen ***,the method could be applied to routine forensic investigations in the future.

关键词： forensic sciences forensic medicine semen stain age estimation spectroscopy Fourier transform infrared chemometrics

The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular Cell sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

Postmortem chest computed tomography for the diagnosis of drowning:a feasibility study

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forensic sciences Research 2021年第2期6卷 152-158页

作者： Junqi Jian Lei Wan Yu Shao Donghua Zou Ping Huang Zhuoqun Wang Ningguo Liu Yijiu Chen Shanghai Key Laboratory of forensic medicine Shanghai Forensic Service PlatformAcademy of Forensic ScienceShanghaiChina department of forensic medicine Soochow UniversitySuzhouChina

It may be difficult to distinguish the cause of death in drowning cases without specific *** aim of this study was to explore the forensic value of thoracic postmortem computed tomography(PMCT)using routine images and three-dimensional(3D)image *** imaging data of PMCT examinations of six drowning cadavers,aged 21-54years,were *** victims of sudden death from coronary artery disease(CAD)were chosen as a control *** 3D bilateral lung images were reconstructed using image processing software,an interactive medical image control system was used to measure and analyze parameters including lung volume,lung volume ratio,mean CT value of the whole lung,and lung CT value distribution *** volume and lung volume ratio were used to assess the shape changes of the *** CT value distribution curves showed the corresponding number of pixels of the different CT values in the lung *** volume was not signifi-cantly larger in drowning cases(mean 2958cm^(3))than in controls(mean 2342cm^(3)).Lung vo-lume ratio values in the drowning group(mean 0.3156)were greater than those in the control group(mean 0.2763);(P=0.02).There was no significant difference between the drowning and control group in the mean CT value of the whole *** were differences between lung CT value distribution curves in drowning victims and controls,with drowning victims showing a single peak and CAD cases showing a bimodal *** PMCT is help-ful for the forensic medical diagnosis of *** volume ratio and lung CT value distri-bution are potential indicators to distinguish between drowning and CAD.

关键词： forensic sciences forensic pathology postmortem CT drowning lung 3D reconstruction CT data

Solid Waste Management:A MADM Approach Using Fuzzy Parameterized Possibility Single-Valued Neutrosophic Hypersoft Expert Settings

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Computer Modeling in Engineering & sciences 2025年第1期142卷 531-553页

作者： Tmader Alballa Muhammad Ihsan Atiqe Ur Rahman Noorah Ayed Alsorayea Hamiden Abd El-Wahed Khalifa department of Mathematics College of SciencesPrincess Nourah bint Abdulrahman UniversityRiyadh11671Saudi Arabia 2 department of Mathematics University of Management and TechnologyLahore54000Pakistan department of Mathematics College of ScienceQassim UniversityBuraydah51452Saudi Arabia

The dramatic rise in the number of people living in cities has made many environmental and social problems *** search for a productive method for disposing of solid waste is the most notable of these *** scholars have referred to it as a fuzzy multi-attribute or multi-criteria decision-making problem using various fuzzy set-like approaches because of the inclusion of criteria and anticipated *** goal of the current study is to use an innovative methodology to address the expected uncertainties in the problem of solid waste site *** characteristics(or sub-attributes)that decision-makers select and the degree of approximation they accept for various options can both be indicators of these *** tackle these problems,a novel mathematical structure known as the fuzzy parameterized possibility single valued neutrosophic hypersoft expert set(ρˆ-set),which is initially described,is integrated with a modified version of Sanchez’s *** this,an intelligent algorithm is *** steps of the suggested algorithm are explained with an example that explains *** compatibility of solid waste management sites and systems is discussed,and rankings are established along with detailed justifications for their *** study’s strengths lie in its application of fuzzy parameterization and possibility grading to effectively handle the uncertainties embodied in the parameters’nature and alternative approximations,*** uses specific mathematical formulations to compute the fuzzy parameterized degrees and possibility grades that are missing from the prior *** is simpler for the decisionmakers to look at each option separately because the decision is *** the computed results,it is discovered that they are consistent and dependable because of their preferred properties.

关键词： Hypersoft expert set Sanchez’s method decision making optimization solid waste management possibility grade fuzzy parameterization

Role of Neuropeptide Y and Peroxisome Proliferator-activated Receptor γ Coactivator-1α in Stress Cardiomyopathy

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Journal of Huazhong University of science and Technology(Medical sciences) 2012年第6期32卷 823-828页

作者：阿兰达王云云朱少华王荣帅周小伟卓荦孙婷怡任亮刘茜董红梅刘艳刘良 department of forensic medicine Tongji Medical CollegeHuazhong University of Science and Technology

Death following situations of intense emotional stress has been linked to the cardiac pathology described as stress cardiomyopathy, whose pathomechanism is still not clear. In this study, we sought to determine, via an animal model, whether the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and the amino peptide neuropeptide Y (NPY) play a role in the pathogenesis of this cardiac entity. Male Sprague-Dawley rats in the experimental group were subjected to immobilization in a plexy glass box for 1 h, which was followed by low voltage elec-tric foot shock for about 1h at 10s intervals in a cage fitted with metallic rods. After 25 days the rats were sacrificed and sections of their hearts were processed. Hematoxylin-eosin staining of cardiac tissues revealed the characteristic cardiac lesions of stress cardiomyopathy such as contraction band necrosis, inflammatory cell infiltration and fibrosis. The semi-quantitative RT-PCR analysis for PGC-1α mRNA expression showed significant overexpression of PGC1-α in the stress-subjected rats (P<0.05). Fluorescence immunohistochemistry revealed a higher production of NPY in the stress-subjected rats as compared to the control rats (P=0.0027). Thus, we are led to conclude that following periods of intense stress, an increased expression of PGC1-α in the heart and an overflow of NPY may lead to stress car-diomyopathy and even death in susceptible victims. Moreover, these markers can be used to identify stress cardiomyopathy as the cause of sudden death in specific cases.

关键词： stress cardiomyopathy peroxisome proliferator-activated receptor γ coactivator-1alpha neuropeptide Y sudden death forensic pathology