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A positive feedback inhibition of isocitrate dehydrogenase 3β on 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 *** 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 *** investigations demonstrated that the knockdown of IDH3βinduced oxidation-phosphorylation uncoupling,leading to reduced energy metabolism and lactate *** 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-transgenic mice,upregulating IDH3βand downregulating PAX6 were found to improve cognitive functioning and reverse AD-like ***,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

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Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/m TOR Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第3期30卷 251-259页

作者： yao Jun-peng FENG Xiu-mei WANG Lu LI Yan-qiu ZHU Zi-yue YAN Xiang-yun YANG Yu-qing LI ying ZHANG Wei Acupuncture and Tuina School Chengdu University of Traditional Chinese MedicineChengdu611137China Department of Rehabilitation Medicine Guanghan People’s HospitalGuanghanSichuan Province618399China Academic Affairs Office Chengdu University of Traditional Chinese MedicineChengdu611137China

Objective:To explore the mechanism of electroacupuncture(EA) in promoting recovery of the facial function with the involvement of autophagy,glial cell line-derived neurotrophic factor(GDNF),and phosphatidylinositol-3-kinase(PI3K)/mammalian target of rapamycin(mTOR) signaling ***:Seventy-two male Sprague-Dawley rats were randomly allocated into the control,sham-operated,facial nerve injury(FNI),EA,EA+3-methyladenine(3-MA),and EA+GDNF antagonist groups using a random number table,with 12 rats in each *** FNI rat model was established with facial nerve crushing *** intervention was conducted at Dicang(ST 4),Jiache(ST 6),Yifeng(SJ 17),and Hegu(LI 4) acupoints for 2 *** Simone’s 10-Point Scale was utilized to monitor the recovery of facial *** histopathological evaluation of facial nerves was performed using hematoxylin-eosin(HE) *** levels of Beclin-1,light chain 3(LC3),and P62 were detected by immunohistochemistry(IHC),immunofluorescence,and reverse transcriptionpolymerase chain reaction,***,IHC was also used to detect the levels of GDNF,Rai,PI3K,and ***:The facial functional scores were significantly increased in the EA group than the FNI group(P<0.05 or P<0.01).HE staining showed nerve axons and myelin sheaths,which were destroyed immediately after the injury,were recovered with EA *** expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats(P<0.01);however,EA treatment reversed these abnormal changes(P<0.01).Meanwhile,EA stimulation significantly increased the levels of GDNF,Rai,PI3K,and mTOR(P<0.01).After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist,the repair effect of EA on facial function was attenuated(P<0.05 or P<0.01).Conclusions:EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of *** may exert this neuroreparative effect through

关键词： electroacupuncture facial nerve injury autophagy glial cell line-derived neurotrophic factor phosphatidylinositol-3-kinase/mammalian target of rapamycin Chinese medicine

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我国公立医院药房改革的实践研究

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卫生经济研究 2018年第7期35卷 6-8页

作者：周亮亮姚银蓥田侃南京中医药大学卫生经济管理学院江苏南京210046

当前,医院药房改革的实践做法主要有药房托管、供应链改造、药房剥离等三种形式。每种形式都存在一定的问题,对此提出相关政策建议:明确禁止开展典型的药房托管,规范指导供应链改造,暂时不提倡推广门诊药房剥离。

关键词：药房托管供应链改造药房剥离

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Effects of PEAR1 gene polymorphism on big endothelin-1 levels in Chinese patients with acute myocardial infarction after percutaneous coronary intervention

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World Journal of Emergency Medicine 2024年第3期15卷 229-231页

作者： Yi yao Na Xu Xiaofang Tang Ce Zhang Sida Jia Jingjing Xu ying Song Xueyan Zhao Runlin Gao Jinqing Yuan Center for Coronary Heart Disease National Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional *** to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is *** contrast,big ET-1.

关键词： coronary percutaneous endothelin

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White matter microstructure mediates the pairwise relationship between childhood maltreatment, microRNA-9, and the severity of major depressive disorder

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中华医学杂志(英文版) 2024年第17期137卷 2140-2142页

作者： Liu Xinyi He Cancan Bai ying Fan Dandan Zang Feifei Zhang Hongxing Zhang Haisan yao Honghong Zhang Zhijun Xie Chunming Department of Neurology Affiliated ZhongDa Hospital School of Medicine Southeast University Nanjing Jiangsu China Neuropsychiatric Research Institute School of Medicine Southeast University Nanjing Jiangsu China Department of Pharmacology School of Medicine Southeast University Nanjing Jiangsu China Henan Key Laboratory of Psychology and Behavior Xinxiang Medical University Xinxiang Henan China Psychology School of Xinxiang Medical University Xinxiang Henan China Department of Radiology Henan Provincial Mental Hospital Xinxiang Medical University Xinxiang Henan China Key Laboratory of Developmental Genes and Human Disease Southeast University Nanjing Jiangsu China

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A deformation criterion of pressurized non-circular cross-section cabin and its effects on cruise performance of BWB civil aircraft

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Chinese Journal of Aeronautics 2024年第6期37卷 78-88页

作者： Siyi GUO Zhenli CHEN Xuanyu yao School of Aeronautics Northwestern Polytechnical UniversityXi’an 710072China Aero Engine Academy of China Beijing 101304China

Blended-Wing-Body(BWB)aircraft is promoted as one of the most possible layouts to achieve more sustainable civil *** to the non-circular cross-section of the center-body,a bulge deformation forms over the upper surface of the body under the coupled loads of the internal pressurization of the cabin and the aerodynamic bending moments of the wing,which reduces the lift-to-drag ratio of BWB *** a limited deformation,the relationship between the aerodynamic performance and the structural weight needs to be *** this work,the effects of stiffness constraints on the center-body deformation,structural weight of the airframe and aerodynamic performance were investigated by using an analytical model of the Pultruded Rod Stitched Efficient Unitized Structure(PRSEUS)for the airframe and the computational fluid dynamics method,*** results show that as the stiffness constraint increases,the spacings between the rod stringers and the frame stiffeners decrease,and the structural weight increases inversely.A 5.2% reduction of the lift-to-drag ratio is encountered at cruise for a medium deformation design of 42.8 mm/m.A higher aerodynamic penalty is suffered when the stiffness constraint is further *** final deformation criterion is different when the weight vector of the aerodynamic performance and structural weight is different.

关键词： Blended-Wing-Body(BWB) Deformation PultrudedRod Stitched Effi-cient Unitized Structure(PRSEUS) Cabin structure Stiffness constraint

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Multi-Robot Cooperative Localization: Time-Varying Unobservable Subspace Analysis and Consistent Algorithm Design

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Journal of Systems Science & Complexity 2024年第5期37卷 1937-1955页

作者： HAO Ning HE Fenghua yao Yu School of Astronautics Harbin Institute of Technology

This paper investigates the problem of cooperative localization(CL) for a multi-robot system(MRS) under dynamic measurement topology, which involves a group of robots collectively estimating their poses with respect to a common reference frame using ego-motion measurements and robot-to-robot relative measurements. The authors provide a theoretical analysis of the time-varying unobservable subspace and propose a consistent cooperative localization algorithm. First, the authors introduce the relative measurement graph(RMG) to represent the relative pose measurements obtained by the MRS at each instant. Then, the authors derive the local observability matrix over a time *** equivalent relationship is established between the local observability matrix and the spectral matrices of the RMG. Moreover, the authors present a method for constructing the unobservable subspace based on the RMG under different topology conditions. Based on this analysis, the authors design a consistent cooperative localization algorithm that satisfies the constraints of the time-varying unobservable subspace. An analytical optimal solution is derived for the constrained optimization *** Carlo numerical simulations are conducted to demonstrate the consistency and accuracy of the proposed method.

关键词： Consistency cooperative localization multi-robot system null space relative measurement graph time-varying unobservable subspace

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Lesson Learned from COVID-19 Retrospective Study: An Entropy-Based Clinical-Interpretable Scorecard for Mortality Risk Control at ICU Admission

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Tsinghua Science and Technology 2024年第1期29卷 34-45页

作者： Chong yao Chonghui Huangqi Anpeng Huang Laboratory of Network Information Security Beihang UniversityBeijing 100191China Andrew and Erna Viterbi School of Engineering University of Southern CaliforniaLos AnglesCA 90089USA Beijing Goodwill Information and Technology Co. Ltd.and Mobile Health LaboratoryPeking UniversityBeijing 100871China

With severe acute respiratory syndrome coronavirus 2 spreading globally and causing 2019 coronavirus disease(COVID-19),a challenge that we unprepared for was about how to optimally plan and distribute limited top-medical resources for patients in need of urgent *** address this challenge,physicians desperately needed a scientific tool to methodically differentiate between cases with varying *** this study,the unique data of COVID-19 intensive care unit(ICU)patients provided by the national medical team in Wuhan were classified into discrete and continuous variable *** continuous data were discretized using an entropy-based method and transformed into serial information margins,in which each information margin is related to a specific symptom or clinical ***,all these native and processed discrete data were used to configure a readable scorecard through logistic regression,which is the desired scientific tool aforementioned.A total of 322 ICU patients(age:[median:64,interquartile range:54-75],males:178[55.28%],and death:72[22.36%])were included in the *** of mortality in COVID-19 patients can be evaluated using a scorecard model(calibration slope:1.343,Brier:0.048,Dxy=0.972,and population stability index=0.071),with desired model performances(accuracy=0.948,area under curve=0.99,sensitivity=1,and specificity=0.939).This new model can interpret clinical meanings from complex data,and compare it with existing machine learning methods through a black-box *** new data-information model answers a critical question of how a computing algorithm produces clinically meaningful results that will help physicians logically allocate medical resources for COVID-19 ***,this tool has limitations,giving that this research is a retrospective ***,this tool will be tested further and optimized for adaptation to similar clinical cases in the future.

关键词： COVID-19 scorecard clinical-interpretable machine learning ICU admission control

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Initial costates derived by near-optimal reference sequence and least-squares method

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Chinese Journal of Aeronautics 2024年第5期37卷 377-391页

作者： Shaozhao LU yao ZHANG Quan HU School of Aerospace Engineering Beijing Institute of TechnologyBeijing 100081China

In this paper,we present a novel initial costates solver for initializing time-optimal trajectory problems in relative motion with continuous low *** proposed solver consists of two primary components:training a Multilayer Perceptron(MLP)for generating reference sequence and Time of Flight(TOF)to the target,and deriving a system of linear algebraic equations for obtaining the initial *** overcome the challenge of generating training samples for the MLP,the backward generation method is proposed to obtain five different training *** training database and sample form are determined by analyzing the input and output correlation using the Pearson correlation *** best-performing MLP is obtained by analyzing the training results with various hyper-parameter combinations.A reference sequence starting from the initial states is obtained by integrating forward with the near-optimal control vector from the output of ***,a system of linear algebraic equations for estimating the initial costates is derived using the reference sequence and the necessary conditions for *** results demonstrate that the proposed initial costates solver improves the convergence ratio and reduce the function calls of the shooting ***,Monte-Carlo simulation illustrates that the initial costates solver is applicable to different initial velocities,demonstrating excellent generalization ability.

关键词： Relative motion Expanding training database Multilayer perceptron Initial costates Least-squares method

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Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress

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Journal of Integrative Medicine 2024年第4期22卷 493-502页

作者： Qian-zhuo Liu Hui Han Xin-ru Fang Lu-yao Wang Dan Zhao Miao-zhu yin Nian Zhang Peng-yu Jiang Zhi-hui Ji Li-min Wu Department of Neurology the First Affiliated Hospital of Anhui University of Chinese MedicineHefei 230031Anhui ProvinceChina Center for Reproduction and Genetics the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230031Anhui ProvinceChina

Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for ***:Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione(GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) ***:Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine,a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron,Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4)expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) ***:Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.

关键词： Berberine Hepatolenticular degeneration Copper deposition Ferroptosis Endoplasmic reticulum stress

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