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Mitophagy in neurodegenerative disease pathogenesis

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Neural Regeneration Research 2024年第5期19卷 998-1005页

作者： Kan Yang Yuqing Yan Anni Yu ru zhang Yuefang zhang Zilong Qiu Zhengyi Li Qianlong zhang Shihao Wu Fei Li Department of Developmental and Behavioural Pediatric&Child Primary Care Brain and Behavioural Research Unit of Shanghai Institute for Pediatric Research and MOE-Shanghai Key Laboratory for Children’s Environmental HealthXinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Center for Excellence in Brain Science and Intelligence Technology Institute of NeuroscienceState Key Laboratory of NeuroscienceCAS Key Laboratory of Primate NeurobiologyChinese Academy of SciencesShanghaiChina College of Materials and Chemical Engineering Hunan Institute of EngineeringXiangtanHunan ProvinceChina School of Medicine Yunnan UniversityKunmingYunnan ProvinceChina Songjiang Research Institute Shanghai Jiao Tong University School of MedicineShanghaiChina Neurosurgery Department Kunming Yenan HospitalKunmingYunnan ProvinceChina

Mitochondria are critical cellular energy resources and are central to the life of the neuron.Mitophagy selectively clears damaged or dysfunctional mitochondria through autophagic machinery to maintain mitochondrial quality control and homeostasis.Mature neurons are postmitotic and consume substantial energy,thus require highly efficient mitophagy pathways to turn over damaged or dysfunctional mitochondria.Recent evidence indicates that mitophagy is pivotal to the pathogenesis of neurological diseases.However,more work is needed to study mitophagy pathway components as potential therapeutic targets.In this review,we briefly discuss the characteristics of nonselective autophagy and selective autophagy,including ERphagy,aggrephagy,and mitophagy.We then introduce the mechanisms of Parkin-dependent and Parkin-independent mitophagy pathways under physiological conditions.Next,we summarize the diverse repertoire of mitochondrial membrane receptors and phospholipids that mediate mitophagy.Importantly,we review the critical role of mitophagy in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.Last,we discuss recent studies considering mitophagy as a potential therapeutic target for treating neurodegenerative diseases.Together,our review may provide novel views to better understand the roles of mitophagy in neurodegenerative disease pathogenesis.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis autophagy mitochondria mitophagy mitophagy receptor Parkin Parkinson’s disease PINK1

Integration of urchin-like MnCo_(2)O_(4)@C core–shell nanowire arrays within porous copper current collector for superior performance Li-ion battery anodes

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Rare Metals 2024年第2期43卷 599-611页

作者： Xue-ru zhang Qiong Wu Yong zhang Xi-Fei Li Ting Xie Yu-Cheng Wu Instrumental Analysis Center Hefei University of TechnologyHefei230009China Key Laboratory of Advanced Functional Materials and Devices of Anhui Province Hefei230009China School of Materials Science and Engineering Hefei University of TechnologyHefei230009China Institute of Advanced Electrochemical Energy Xi’an University of TechnologyXi’an710048China

Spinel MnCo_(2)O_(4) is a promising energy storage candidate as anode materials in lithium-ion batteries owing to synergistic effects of two intrinsic solid-state redox couples.However,low conductivity,poor rate capacity and rapid capacity fading have seriously impaired its practical applications.To overcome the inferiorities,urchin-like MnCo_(2)O_(4)@C core–shell nanowire arrays have been fabricated directly within a porous copper current collector via a facile hydrothermal method followed by a chemical vapor deposition carbonization process.In a typical nanowire,the core is composed of interconnected MnCo_(2)O_(4)nanoparticles and the shell shows as a thin amorphous carbon layer.The integrated MnCo_(2)O_(4)@C/Cu structure could act as working anodes without using additives or polymer binders.While MnCo_(2)O_(4)@C/Cu possesses slightly longer Li-ion insertion/desertion pathway than that of MnCo_(2)O_(4)/Cu,the carbon shell could effectively prevent the pulverization of MnCo_(2)O_(4) and lower down charge transfer resistance and actively participate in Li-ion cycles.The rearrangement of carbon atoms during lithiation/delithiation cycling could inhibit the formation of passive solid electrolyte interphase films.As a result,the MnCo_(2)O_(4)@C/Cu electrode presents superior rate capacity(600 mAh·g^(−1) at 1 A·g^(−1)) and better stability(797 mAh·g^(−1) after 200 cycles at 100 mA·g^(−1)).The excellent reversible Li ion storage capacity,cycling stability and rate capacity endow MnCo_(2)O_(4)@C/Cu great potential as stable and high output integrated anode materials in Li-ion batteries.

关键词： MnCo_(2)O_(4)@C Urchin-like nanowire arrays Core-shell Integrated anode materials Lithium-ion batteries

Blast damage zone strength reduction method for deep cavern excavation and its application

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Frontiers of Structural and Civil Engineering 2024年第2期18卷 236-251页

作者： Tianzhi YAO Zuguo MO Li QIAN Yunpeng GAO Jianhai zhang Xianglin XING Enlong LIU ru zhang State Key Laboratory of Hydraulics and Mountain River Engineering College of Water Resources and HydropowerSichuan UniversityChengdu 610065China Power China Chengdu Engineering Corporation Limited Chengdu 610072China

The drill and blast(D&B)method is widely used to excavate underground spaces,but explosions generally cause damage to the rock.Still,no blast simulation method can provide computational accuracy and efficiency.In this paper,a blast equivalent simulation method called the blast damage zone strength reduction(BDZSR)method is proposed.This method first calculates the range of the blast-induced damage zone(BDZ)by formulae,then reduces the strength and deformation parameters of the rock within the BDZ ahead of excavation,and finally calculates the excavation damage zone(EDZ)for the D&B method by numerical simulation.This method combines stress wave attenuation,rock damage criteria and stress path variation to derive the BDZ depth calculation formulae.The formulae consider the initial geo-stress,and the reliability is verified by numerical simulations.The calculation of BDZ depth with these formulae allows the corresponding numerical simulation to avoid the time-consuming dynamic calculation process,thus greatly enhancing the calculation efficiency.The method was applied to the excavation in Jinping Class II hydropower station to verify its feasibility.The results show that the BDZSR method can be applied to blast simulation of underground caverns and provide a new way to study blast-induced damage.

关键词： attenuation of stress wave deep-buried underground building drill and blast in situ stress

Endogenous biosynthesis of docosahexaenoic acid(DHA)regulates fish oocyte maturation by promoting pregnenolone production

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Zoological Research 2024年第1期45卷 176-188页

作者： Yi Li Xuehui Li Ding Ye ru zhang Chengjie Liu Mudan He Houpeng Wang Wei Hu Yonghua Sun State Key Laboratory of Freshwater Ecology and Biotechnology Institute of HydrobiologyInnovation Academy for Seed DesignChinese Academy of SciencesWuhanHubei 430072China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China Hubei Hongshan Laboratory WuhanHubei 430070China

Omega-3 polyunsaturated fatty acids(n-3 PUFAs),particularly docosahexaenoic acid(22:6n-3,DHA),play crucial roles in the reproductive health of vertebrates,including humans.Nevertheless,the underlying mechanism related to this phenomenon remains largely unknown.In this study,we employed two zebrafish genetic models,i.e.,elovl2^(-/-)mutant as an endogenous DHAdeficient model and fat1(omega-3 desaturase encoding gene)transgenic zebrafish as an endogenous DHA-rich model,to investigate the effects of DHA on oocyte maturation and quality.Results show that the elovl2^(-/-)mutants had much lower fecundity and poorer oocyte quality than the wild-type controls,while the fat1 zebrafish had higher fecundity and better oocyte quality than wildtype controls.DHA deficiency in elovl2^(-/-)embryos led to defects in egg activation,poor microtubule stability,and reduced pregnenolone levels.Further study revealed that DHA promoted pregnenolone synthesis by enhancing transcription of cyp11a1,which encodes the cholesterol side-chain cleavage enzyme,thereby stabilizing microtubule assembly during oogenesis.In turn,the hypothalamic-pituitary-gonadal axis was enhanced by DHA.In conclusion,using two unique genetic models,our findings demonstrate that endogenously synthesized DHA promotes oocyte maturation and quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.

关键词： Docosahexaenoic acid Oocyte maturation Oocyte quality Pregnenolone Microtubule

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

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Journal of Geriatric Cardiology 2024年第4期21卷 443-457页

作者： Jing-Yue XU Zheng-Kai XUE Ya-ru zhang Xing LIU Xue zhang Xi YANG Tong LIU Kang-Yin CHEN Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of Cardiologythe Second Hospital of Tianjin Medical UniversityTianjinChina

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.METHODS A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fcgroup.CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inh

关键词： remodeling cardiac inhibited

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1514-1531页

作者： Yong Pan Yi-ru zhang Ling-Yun Wang Li-Na Wu Ying-Qiu Ma Zhou Fang Shi-Bo Li Department of Infectious Disease Zhoushan HospitalWenzhou Medical UniversityZhoushan 316021Zhejiang ProvinceChina State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital of Zhejiang UniversityHangzhou 310003Zhejiang ProvinceChina Department of Infectious Disease The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina

BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain dismal.AIM To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database.Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples.The targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan database.The univariate and multivariate analysis were utilized to identify independent prognostic indicators.RESULTS CDKN2A was frequently mutated and deleted in HCC.The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways.The CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully established.GAS5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC patients.The association between GAS5 expression and methylation,immune infilt-ration was explored.Besides,traditional Chinese medicine effective components targeting GAS5 were obtained.CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression.Moreover,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

关键词： Hepatocellular carcinoma Competitive endogenous RNA Molecular mechanism Prognosis Biomarker

Fragility crossover mediated by covalent-like electronic interactions in metallic liquids

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Materials Futures

Materials Futures 2024年第2期3卷 117-130页

作者： Hui-ru zhang Liang Gao Yu-Hao Ye Jia-Xin zhang Tao zhang Qing-Zhou Bu Qun Yang Zeng-Wei Zhu Shuai Wei Hai-Bin Yu Wuhan National High Magnetic Field Center and School of Physics Huazhong University of Science and TechnologyWuhan 430074People’s Republic of China Department of Chemistry Aarhus University8000 AarhusDenmark iMAT Centre for Integrated Materials Research Aarhus University8000 AarhusDenmark

Fragility is one of the central concepts in glass and liquid sciences,as it characterizes the extent of deviation of viscosity from Arrhenius behavior and is linked to a range of glass properties.However,the intervention of crystallization often prevents the assessment of fragility in poor glass-formers,such as supercooled metallic liquids.Hence experimental data on their compositional dependence are scarce,let alone fundamentally understood.In this work,we use fast scanning calorimetry to overcome this obstacle and systematically study the fragility in a ternary La–Ni–Al system,over previously inaccessible composition space.We observe fragility dropped in a small range with the Al alloying,indicating an alloying-induced fragility crossover.We use x-ray photoelectron spectroscopy,resistance measurements,electronic structure calculations,and DFT-based deep-learning atomic simulations to investigate the cause of this fragility drop.These results show that the fragility crossover can be fundamentally ascribed to the electronic covalency associated with the unique Al–Al interactions.Our findings provide insight into the origin of fragility in metallic liquids from an electronic structure perspective and pave a new way for the design of metallic glasses.

关键词： metallic glass fragility fast scanning calorimetry density functional theory deep learning potential

Dynamic mechanical characteristics of deep Jinping marble in complex stress environments

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第2期16卷 630-644页

作者： Chendi Lou Heping Xie ru zhang Hai Ren Hao Luo Kun Xiao Yuan Peng Qiang Tan Li Ren Institute for Disaster Management and Reconstruction Sichuan UniversityChengdu610207China College of Water Resource&Hydropower Sichuan UniversityChengdu610065China MOE Key Laboratory of Deep Earth Science&Engineering Sichuan UniversityChengdu610065China Yalong River Hydropower Development Company Ltd.Chengdu610051China (Chongqing)International Engineering Technology Company Ltd.Chongqing401121China

To reveal the dynamic mechanical characteristics of deep rocks,a series of impact tests under triaxial static stress states corresponding to depths of 300-2400 m were conducted.The results showed that both the strain rates and the stress environments in depth significantly affect the mechanical characteristics of rocks.The sensitivity of strain rate to the dynamic strength and deformation modulus shows a negative correlation with depth,indicating that producing penetrative cracks in deep environments is more difficult when damage occurs.The dynamic strength shows a tendency to decrease and then increase slightly,but decreases sharply finally.Transmissivity demonstrates a similar trend as that of strength,whereas reflectivity indicates the opposite trend.Furthermore,two critical depths with high dynamically induced hazard possibilities based on the China Jinping Underground Laboratory(CJPL)were proposed for deep engineering.The first critical depth is 600-900 m,beyond which the sensitivity of rock dynamic characteristics to the strain rate and restraint of circumferential stress decrease,causing instability of surrounding rocks under axial stress condition.The second one lies at 1500-1800 m,where the wave impedance and dynamic strength of deep surrounding rocks drop sharply,and the dissipation energy presents a negative value.It suggests that the dynamic instability of deep surrounding rocks can be divided into dynamic load dominant and dynamic load induced types,depending on the second critical depth.

关键词： Rock mechanics Split-Hopkinson pressure bar Coupled static‒dynamic loading Different depths Holmquist-Johnson-Cook(HJC)model

Simultaneous determination of 6 carbamate pesticides and relevant metabolites in oilseeds and oil with the modified fast QuEChERS method by ultra-performance liquid chromatography-tandem mass spectrometry

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未来食品学报(英文) 2024年第1期4卷 97-104页

作者： Bangben Yao Yun Li ru zhang Li Yao Jianguo Xu Chao Yan Wei Chen Anui Province Inustinute of Prodtuct Quality Supenvision&Inspection Hefei 230051China Engineering Reseanch Center of Bio-Proess MOESchool of Food cand Biological EngineerngHefei University of TechmologyHefei 230009China School of Ijfe Science Anhui UniversityHefei 230601China

A sensitive and reliable method was developed and validated for the simu1taneous determination of 6 carbamate pesticides and relevant metabolites based on the modified fast QuEChERS(quick,easy,cheap,effective,rugged and safe)method combined with ultra-performance 1iquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The method was also applied in the analysis of 23 commonly consumed oilseeds and oil samples.The sample was extracted with acetonitrile for three times and then the extracted solution was filtered directly though 250 mg precipitated silica adsorbent(PSA)and 250 mg Cis The mobile phase was water(containing 0.1%formic acid)and acetonitrile.The extemal standard protocols were adopted to validate the method in terms of recovery,1inearity,precision,sensitivity,and relative standard deviation(RSD)under the optimized conditions.The linear calibration curves with different ranges were established with R^(2)>0.9973,limit of detections(LODs)ranged from 0.100μg/kg to 20000μg/kg and limit of quantitations(LOQs)ranged from 0.300μg/kg to 6.000μg/kg.The LODs meets the detection requirement for the maximum residue limits in practical samples.Meanwhile,the recoveries ranged from 60.2%to 116.6%with associated RSDs ranged from 0.33%to 5.35%in 10 oilseeds matrices and ranged from 61.9%to 116.9%with RSDs ranged from 0.30%to 5.02%in 13 oil matrices.These features do make the UPLC-MSMS an ideal analytical platform for accurate and high throughput analysis of carbamates residues in the complex matrix.

关键词： Carbamate pesticides Oiseeds and oil Dispersive solid-phase extraction U1tra-performance 1iquid chromatography-tandem mass spectometry Simu1taneous determination High throughput