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A positive feedback inhibition of isocitrate dehydrogenase 3βon paired-box gene 6 promotes Alzheimer-like pathology

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2324-2340页

作者： Xin Wang Qian Liu hai-tao Yu Jia-zhao xie Jun-ning Zhao Zhi-ting Fang Min Qu Yao Zhang Ying Yang jian-Zhi Wang Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Fundamental Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu 214122China Hubei Provincial Key Laboratory for Applied Toxicology Hubei Provincial Center for Disease Control and PreventionHubei Provincial Academy of Preventive MedicineWuhan 430000China Endocrine Department of Liyuan Hospital Key Laboratory of Ministry of Education of China for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226000China

Impaired brain glucose metabolism is an early indicator of Alzheimer’s disease(AD);however,the fundamental mechanism is unknown.In this study,we found a substantial decline in isocitrate dehydrogenase 3β(IDH3β)levels,a critical tricarboxylic acid cycle enzyme,in AD patients and AD-transgenic mice’s brains.Further investigations demonstrated that the knockdown of IDH3βinduced oxidation-phosphorylation uncoupling,leading to reduced energy metabolism and lactate accumulation.The resulting increased lactate,a source of lactyl,was found to promote histone lactylation,thereby enhancing the expression of paired-box gene 6(PAX6).As an inhibitory transcription factor of IDH3β,the elevated PAX6 in turn inhibited the expression of IDH3β,leading to tau hyperphosphorylation,synapse impairment,and learning and memory deficits resembling those seen in AD.In AD-transgenic mice,upregulating IDH3βand downregulating PAX6 were found to improve cognitive functioning and reverse AD-like pathologies.Collectively,our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3β-lactate-PAX6-IDH3β.Breaking this loop by upregulating IDH3βor downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

关键词： metabolism Alzheimer impaired

The reaction mechanism and interfacial crystallization of Al nanoparticle-embedded Ni under shock loading

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Defence Technology（防务技术） 2024年第3期33卷 114-124页

作者： Yifan xie jian-Li Shao Rui Liu Pengwan Chen State Key Laboratory of Explosion Science and Technology Beijing Institute of TechnologyBeijing100081China Explosion Protection and Emergency Disposal Technology Engineering Research Center of the Ministry of Education Beijing100039China

The shock-induced reaction mechanism and characteristics of Ni/Al system,considering an Al nanoparticle-embedded Ni single crystal,are investigated through molecular dynamics simulation.For the shock melting of Al nanoparticle,interfacial crystallization and dissolution are the main characteristics.The reaction degree of Al particle first increases linearly and then logarithmically with time driven by rapid mechanical mixing and following dissolution.The reaction rate increases with the decrease of particle diameter,however,the reaction is seriously hindered by interfacial crystallization when the diameter is lower than 9 nm in our simulations.Meanwhile,we found a negative exponential growth in the fraction of crystallized Al atoms,and the crystallinity of B2-NiAl(up to 20%)is positively correlated with the specific surface area of Al particle.This can be attributed to the formation mechanism of B2-NiAl by structural evolution of finite mixing layer near the collapsed interface.For shock melting of both Al particle and Ni matrix,the liquid-liquid phase inter-diffusion is the main reaction mechanism that can be enhanced by the formation of internal jet.In addition,the enhanced diffusion is manifested in the logarithmic growth law of mean square displacement,which results in an almost constant reaction rate similar to the mechanical mixing process.

关键词： Shock-induced reaction Molecular dynamics simulations Interfacial crystallization Reaction mechanism

Cerebral furin deficiency causes hydrocephalus in mice

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Genes & Diseases 2024年第3期11卷 438-451页

作者： Shiqi xie Xiaoyong xie Jing Tang Biao Luo jian Chen Qixin Wen jianrong Zhou Guojun Chen Nursing College Chongqing Medical UniversityChongqing 400016China Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Major Neurological and Mental DisordersChongqing Key Laboratory of NeurologyChongqing 400016China

Furin is a pro-protein convertase that moves between the trans-Golgi network and cell surface in the secretory pathway.We have previously reported that cerebral overexpres-sion of furin promotes cognitive functions in mice.Here,by generating the brain-specific furin conditional knockout(ckO)mice,we investigated the role of furin in brain development.We found that furin deficiency caused early death and growth retardation.Magnetic resonance im-aging showed severe hydrocephalus.In the brain of furin cko mice,impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expres-sion of RAB28,a ciliary vesicle protein.In line with the widespread neuronal loss,ependymal cell layers were damaged.Further proteomics analysis revealed that cell adhesion molecules including astrocyte-enriched ITGB8 and BCAR1 were altered in furin cKO mice;and astrocyte overgrowth was accompanied by the reduced expression of sox9,indicating a disrupted differ-entiation into ependymal cells.Together,whereas alteration of RAB28 expression correlated with the role of vesicle trafficking in ciliogenesis,dysfunctional astrocytes might be involved in ependymal damage contributing to hydrocephalus in furin ckO mice.The structural and mo-lecular alterations provided a clue for further studying the potential mechanisms of furin.

关键词： Astrocyte Ciliogenesis Conditionalknockout Ependymal Furin Hydrocephalus Proteomics

A DFT study on Pt single atom loaded COF for efficient photocatalytic CO_(2)reduction

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Journal of Materials Science & Technology 2024年第3期170卷 87-94页

作者： Fei xie Chuanbiao Bie jian Sun Zhenyi Zhang Bicheng Zhu Laboratory of Solar Fuel Faculty of Materials Science and ChemistryChina University of GeosciencesWuhan430078China Key Laboratory of New Energy and Rare Earth Resource Utilization of State Ethnic Affairs Commission Key Laboratory of Photosensitive Materials and Devices of Liaoning ProvinceSchool of Physics and Materials EngineeringDalian Minzu UniversityDalian116600China

Photocatalytic CO_(2)reduction provides a promising strategy for the alleviation of greenhouse effect and energy shortage problem.Metal single atom modification is an effective method to improve the CO_(2)reduction performance of covalent organic framework(COF)photocatalysts,while the intrinsic mechanism is not revealed in depth.Herein,a Pt-COF photocatalytic system was constructed by embedding Pt single atom in TFPT-TMT-COF(TFPT:1,3,5-tris(4-formylphenyl)-triazine,TMT:2,4,6-trimethyl-1,3,5-triazine).Based on density functional theory(DFT)calculation,the geometric structure and electronic property of Pt-COF were investigated,and the CO_(2)adsorption and reduction reaction process on Pt-COF were simulated.The results show that the Pt atom can be steadily anchored in COF via the formation of Pt-N and Pt-C bonds.Moreover,there is strong electronic interaction between Pt and COF.The incorporation of Pt atom benefits the CO_(2)reduction activity of COF from multiple aspects:(ⅰ)reducing the band gap and improving light absorption;(ⅱ)enhancing CO_(2)adsorption and activating the CO_(2)molecule;(ⅲ)decreasing the energy barrier in the hydrogenation step of CO_(2)→COOH,thus facilitating CO_(2)conversion to CO;(ⅳ)inhibiting the hydrogenation of CO,thereby increasing the selectivity of CO.This work brings a novel insight into the excellent CO_(2)reduction performance of Pt modified COF,and provides useful references for the design of single atom photocatalysts.

关键词： Photocatalysis Carbon dioxide reduction Covalent organic framework Pt single atom Theoretical calculation

Algorithms and statistical analysis for linear structured weighted total least squares problem

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Geodesy and Geodynamics 2024年第2期15卷 177-188页

作者： jian xie Tianwei Qiu Cui Zhou Dongfang Lin Sichun Long School of Earth Science and Spatial Information Engineering Hunan University of Science and TechnologyXiangtan 411201China College of Science Central South University of Forestry and TechnologyChangsha 410018China National-Local Joint Engineering Laboratory of Geo-spatial Information Technology Hunan University of Science and TechnologyXiangtan 411201China

Weighted total least squares(WTLS)have been regarded as the standard tool for the errors-in-variables(EIV)model in which all the elements in the observation vector and the coefficient matrix are contaminated with random errors.However,in many geodetic applications,some elements are error-free and some random observations appear repeatedly in different positions in the augmented coefficient matrix.It is called the linear structured EIV(LSEIV)model.Two kinds of methods are proposed for the LSEIV model from functional and stochastic modifications.On the one hand,the functional part of the LSEIV model is modified into the errors-in-observations(EIO)model.On the other hand,the stochastic model is modified by applying the Moore-Penrose inverse of the cofactor matrix.The algorithms are derived through the Lagrange multipliers method and linear approximation.The estimation principles and iterative formula of the parameters are proven to be consistent.The first-order approximate variance-covariance matrix(VCM)of the parameters is also derived.A numerical example is given to compare the performances of our proposed three algorithms with the STLS approach.Afterwards,the least squares(LS),total least squares(TLS)and linear structured weighted total least squares(LSWTLS)solutions are compared and the accuracy evaluation formula is proven to be feasible and effective.Finally,the LSWTLS is applied to the field of deformation analysis,which yields a better result than the traditional LS and TLS estimations.

关键词： Linear structured weighted total least squares Errors-in-variables Errors-in-observations Functional modelmodification Stochastic model modification Accuracyevaluation

What benefit can be obtained from magnetic resonance imaging diagnosis with artificial intelligence in prostate cancer compared with clinical assessments?

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Military Medical Research 2024年第2期11卷 268-286页

作者： Li-Tao Zhao Zhen-Yu Liu Wan-Fang xie Li-Zhi Shao jian Lu Jie Tian jian-Gang Liu School of Engineering Medicine Beihang UniversityBeijing 100191China School of Biological Science and Medical Engineering Beihang UniversityBeijing 100191China CAS Key Laboratory of Molecular Imaging Institute of AutomationBeijing 100190China University of Chinese Academy of Sciences Beijing 100080China Department of Urology Peking University Third HospitalPeking UniversityBeijing 100191China Key Laboratory of Big Data‑Based Precision Medicine(Beihang University) Ministry of Industry and Information Technology of the People's Republic of ChinaBeijing 100191China Beijing Engineering Research Center of Cardiovascular Wisdom Diagnosis and Treatment Beijing 100029China

The present study aimed to explore the potential of artificial intelligence(AI)methodology based on magnetic resonance(MR)images to aid in the management of prostate cancer(PCa).To this end,we reviewed and summarized the studies comparing the diagnostic and predictive performance for PCa between AI and common clinical assessment methods based on MR images and/or clinical characteristics,thereby investigating whether AI methods are generally superior to common clinical assessment methods for the diagnosis and prediction fields of PCa.First,we found that,in the included studies of the present study,AI methods were generally equal to or better than the clinical assessment methods for the risk assessment of PCa,such as risk stratification of prostate lesions and the prediction of therapeutic outcomes or PCa progression.In particular,for the diagnosis of clinically significant PCa,the AI methods achieved a higher summary receiver operator characteristic curve(SROC-AUC)than that of the clinical assessment methods(0.87 vs.0.82).For the prediction of adverse pathology,the AI methods also achieved a higher SROC-AUC than that of the clinical assessment methods(0.86 vs.0.75).Second,as revealed by the radiomics quality score(RQS),the studies included in the present study presented a relatively high total average RQS of 15.2(11.0–20.0).Further,the scores of the individual RQS elements implied that the AI models in these studies were constructed with relatively perfect and standard radiomics processes,but the exact generalizability and clinical practicality of the AI models should be further validated using higher levels of evidence,such as prospective studies and open-testing datasets.

关键词： Clinically significant prostate cancer Adverse pathology Radiomics quality score Artificial intelligence Magnetic resonance imaging

Adaptive detection of range-spread targets in homogeneous and partially homogeneous clutter plus subspace interference

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Journal of Systems Engineering and Electronics 2024年第1期35卷 43-54页

作者： jian Tao HE Jia WANG Bencai LIU Yu XU Congan xie Zikeng Research Institute of Information Fusion Naval Aviation UniversityYantai 264001China Air Force Early Warning Academy Wuhan 430019China

Adaptive detection of range-spread targets is considered in the presence of subspace interference plus Gaussian clutter with unknown covariance matrix.The target signal and interference are supposed to lie in two linearly independent subspaces with deterministic but unknown coordinates.Relying on the two-step criteria,two adaptive detectors based on Gradient tests are proposed,in homogeneous and partially homogeneous clutter plus subspace interference,respectively.Both of the proposed detectors exhibit theoretically constant false alarm rate property against unknown clutter covariance matrix as well as the power level.Numerical results show that,the proposed detectors have better performance than their existing counterparts,especially for mismatches in the signal steering vectors.

关键词： adaptive detection subspace interference constant false alarm rate Gradient test partially homogeneous environment

A resonant high-pressure microsensor based on a composite pressure-sensitive mechanism of diaphragm bending and volume compression

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Microsystems & Nanoengineering 2024年第2期10卷 57-66页

作者： Pan Qian Zongze Yu Jie Yu Yulan Lu Bo xie jian Chen Deyong Chen Junbo Wang The State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of SciencesBeijing100190China The School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of SciencesBeijing100049China

In this paper,a composite pressure-sensitive mechanism combining diaphragm bending and volume compression was developed for resonant pressure microsensors to achieve high-pressure measurements with excellent accuracy.The composite mechanism was explained,and the sensor structure was designed based on theoretical analysis and finite element simulation.An all-silicon resonant high-pressure microsensor with multiple miniaturized cavities and dual resonators was developed,where dual resonators positioned in two resonant cavities with suitably different widths are used to perform opposite characteristics in pressure and the same characteristics at different temperatures,which can improve pressure sensitivities and realize temperature self-compensation by differential frequency output.The microsensor was fabricated by microfabrication,and the experimental results showed that the sensor had an accuracy of±0.015%full scale(FS)in a pressure range of 0.1~100 MPa and a temperature range of−10~50℃.The pressure sensitivity of the differential frequency was 261.10 Hz/MPa(~2523 ppm/MPa)at a temperature of 20℃,and the temperature sensitivities of the dual resonators were−1.54 Hz/℃(~−14.5 ppm/℃)and−1.57 Hz/℃(~−15.6 ppm/℃)at a pressure of 2 MPa.The differential output had an outstanding stability within±0.02 Hz under constant temperature and pressure.Thus,this research provides a convenient solution for high-pressure measurements because of its advantages,namely,large range,excellent accuracy and stability.

关键词： stability. resonant bending

Multiple interface coupling on natural tourmaline enables high-efficiency removal of antibiotic:Superior property and mechanism

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Journal of Environmental Sciences 2024年第6期140卷 242-254页

作者： Jingjing Cui Xiangyu Liu Feifan Qie Chengzhe xie Qingdong He jian Liu Steven L.Suib Wenbo Wang College of Chemistry and Chemical Engineering Inner Mongolia UniversityHohhot 010021China Department of Chemistry University of ConnecticutStorrsCT 06269-3060United States

Reasonably designing highly active,environmentally friendly,and cost-effective catalysts for efficient elimination of pollutants from water is desirable but challenging.Herein,an efficient heterogeneous photo-Fenton catalyst tourmaline(TM)/tungsten oxide(WO_(3-x))(named TW10)containing tungsten/boron/iron(W/B/Fe)synergistic active centers and 90%of cheap natural tourmaline(TM)mineral rich in Fe and B elements.The TW10 catalyst can quickly activate peroxymonosulfate(PMS)to generate massive active free radicals,which may induce the rapid and efficient degradation of tetracycline(TC).The TW10/PMS/Visible light system can effectively degrade up to 98.7%of tetracycline(TC)in actual waters(i.***.seawater,Yellow River,and Yangtze River water),and the catalytic degradation rates reach 1.65,5.569,and 2.38 times higher than those of TM,WO_(3-x),and commercial P25(Degussa,Germany),respectively.In addition,the catalyst can be recycled and reused multiple times.Electron spin resonance spectroscopy(EPR),X-ray photoelectron spectroscopy(XPS),and liquid chromatograph-mass spectrometer(LC-MS)analyses confirm that the synergistic catalytic effect of W/B/Fe sites on the TW10 catalyst accelerates the electron transfer between Fe(Ⅱ)and Fe(Ⅲ),as well as between W(Ⅴ)and W(Ⅵ),and thus promotes the rapid degradation of TC.The catalytic reaction mechanism and degradation pathway of TC were explored.This work provides a feasible route for the design and development of new eco-friendly and efficient catalyst.

关键词： Tourmaline(TM) Fenton-like catalyst Tungsten oxide Peroxymonosulfate Antibiotic