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Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

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Acta Pharmaceutica Sinica B 2024年第2期14卷 437-454页

作者： Jiamei Le Yilong chen Wei Yang Ligong chen Jianping ye Shanghai Key Laboratory of Molecular Imaging Zhoupu HospitalShanghai University of Medicine and Health SciencesShanghai 201318China School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China Metabolic Disease Research Center Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450007China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Research Center for Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter proteins.These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions.They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

关键词： Solute carriers(SLCs) Energ ymetabolism ATP production Type 2 diabetes mellitus(T2DM) Glucose homeostasis Polymorphisms

Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

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Neural Regeneration Research 2024年第7期19卷 1489-1498页

作者： Jinwang ye Huali Wan Sihua chen Gong-Ping Liu Shenzhen Key Laboratory of Marine Biotechnology and Ecology College of Life Sciences and OceanographyShenzhen UniversityShenzhenGuangdong ProvinceChina Department of Laboratory Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neurodegeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

关键词： acetylation Alzheimer’s disease cognitive deficits gliosis mitochondria damage neuroinflammation phosphorylation synaptic impairments tau tau immunotherapy

Diagnostic values of questionnaires of Convergence Insufficiency Symptom Survey and College of Optometrists Vision Development Quality of Life in the screening of convergence insufficiency

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 904-908页

作者： Ling Xiong Qian chen ye Wu Department of Ophthalmology West China HospitalSichuan University/Laboratory of Optometry and Vision ScienceWest China School of MedicineChengdu 610041Sichuan ProvinceChina Department of Clinical Research Management Center of BiostatisticsDesignMeasurement and EvaluationWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

AIM:To compare and analyse the diagnostic efficacy of the College of Optometrists Vision Development Quality of Life Questionnaire(COVD-QOL)and the Convergence Insufficiency Symptom Survey(CISS)in detecting convergence insufficiency and to compare their diagnostic value in clinical applications.METHODS:Using the diagnostic test method,62 adult patients with convergence insufficiency(age:24.74±3.75y)and 62 normal participants(age:23.61±3.13y)who visited the Optometry Clinic of West China Hospital of Sichuan University from April 2021 to January 2023 were included.All subjects completed the CISS and COVD-QOL.Statistical analysis of the sensitivity and specificity of the CISS and COVD-QOL and comparison and joint experimental analysis of their diagnostic efficacy were performed.RESULTS:The sensitivity of the CISS and COVD-QOL for convergence insufficiency was 64.5%and 71.0%,respectively,while the specificity was 96.8%and 67.7%,respectively.Compared to the CISS alone,the combination of the CISS and COVD-QOL demonstrated lower sensitivity and specificity.The areas under the receiver operating characteristic curve of CISS,COVD-QOL and CISS combined with COVD-QOL were 0.806,0.694 and 0.782,respectively.CONCLUSION:Considering the low sensitivity of the CISS and the low specificity of the COVD-QOL,it is recommended to supplement these questionnaires with other screening tests for the detection of convergence insufficiency.

关键词： convergence insufficiency symptom survey College of Optometrists Vision Development Quality of Life Questionnaire convergence insufficiency asthenopia

SDGNN: Symmetry-Preserving Dual-Stream Graph Neural Networks

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IEEE/CAA Journal of Automatica Sinica 2024年第7期11卷 1717-1719页

作者： Jiufang chen ye Yuan Xin Luo the College of Computer Science and Technology Chongqing University of Posts and TelecommunicationsChongqing 400065 the Chongqing Key Laboratory of Big Data and Intelligent Computing Chongqing Institute of Green and Intelligent TechnologyChinese Academy of SciencesChongqing 400714China the College of Computer and Information Science Southwest UniversityChongqing 400715China IEEE

Dear Editor,This letter proposes a symmetry-preserving dual-stream graph neural network(SDGNN) for precise representation learning to an undirected weighted graph(UWG). Although existing graph neural networks(GNNs) are influential instruments for representation learning to a UWG, they invariably adopt a unique node feature matrix for illustrating the sole node set of a UWG.

关键词： representation preserving undirected

Rotor cross-tilt optimization for yaw control improvement of multi-rotor eVTOL aircraft

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Chinese Journal of Aeronautics 2024年第3期37卷 153-167页

作者： Xufei YAN ye YUAN Yanqin ZHAO Renliang chen Zhejiang Lab Hangzhou 311100China Department of Aerospace Engineering Swansea UniversitySwanseaWales SA28PPUK National Key Laboratory of Rotorcraft Aeromechanics Nanjing University of Aeronautics and AstronauticsNanjing 210016China

Manned multi-rotor electric Vertical Takeoff and Landing(eVTOL)aircraft is prone to actuator saturation due to its weak yaw control efficiency.To address this inherent problem,a rotor cross-tilt configuration is applied in this paper,with an optimization method proposed to improve the overall control efficiency of the vehicle.First,a flight dynamics model of a 500-kg manned multi-rotor eVTOL aircraft is established.The accuracy of the co-axial rotor model is verified using a single arm test bench,and the accuracy of the flight dynamics model is verified by the flight test data.Then,an optimization method is designed based on the flight dynamics model to calculate an optimal rotor cross-tilt mounting angle,which not only improves the yaw control efficiency,but also basically maintains the efficiency of other control channels.The ideal rotor cross-tilt mounting angle for the prototype is determined by comprehensively considering the optimal results with different payloads,forward flight speeds,and rotor mounting angle errors.Finally,the feasibility of the rotor cross-tilt mounting angle is proved by analyzing the control derivatives of the flight dynamics model,the test data of a ground three Degree-of-Freedom(3DOF)platform,and the actual flight data of the prototype.The results show that a fixed rotor cross-tilt mounting angle can achieve ideal yaw control effectiveness,improving yaw angle tracking and hold ability,increasing endurance time,and achieving good yaw control performance with different payloads and forward speeds.

关键词： Multi-rotor eVTOL Control efficiency Flight dynamics model Cross-tilt optimization Endurance time

Deep Video Harmonization by Improving Spatial-temporal Consistency

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Machine Intelligence Research 2024年第1期21卷 46-54页

作者： Xiuwen chen Li Fang Long ye Qin Zhang Key Laboratory of Media Audio and Video Ministry of Education Communication University of ChinaBeijing 100024China

Video harmonization is an important step in video editing to achieve visual consistency by adjusting foreground appear-ances in both spatial and temporal dimensions.Previous methods always only harmonize on a single scale or ignore the inaccuracy of flow estimation,which leads to limited harmonization performance.In this work,we propose a novel architecture for video harmoniza-tion by making full use of spatiotemporal features and yield temporally consistent harmonized results.We introduce multiscale harmon-ization by using nonlocal similarity on each scale to make the foreground more consistent with the background.We also propose a fore-ground temporal aggregator to dynamically aggregate neighboring frames at the feature level to alleviate the effect of inaccurate estim-ated flow and ensure temporal consistency.The experimental results demonstrate the superiority of our method over other state-of-the-art methods in both quantitative and visual comparisons.

关键词： Harmonization temporal consistency video editing video composition nonlocal similarity

Advancing electrochemical drilling process via coupling of flow field and electric field in pulsating state generated by a novel tube tool

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Chinese Journal of Aeronautics 2024年第4期37卷 542-555页

作者： Liang chenG Xiaolei chen Zhisen ye Yongjun ZHANG State Key Laboratory of Precision Electronic Manufacturing Technology and Equipment Guangdong University of TechnologyGuangzhou 510006China Guangdong Key Laboratory of Advanced Manufacturing Technology of Marine Energy Equipment Guangdong University of TechnologyGuangzhou 510006China Guangzhou Key Laboratory of Nontraditional Machining and Equipment Guangdong University of TechnologyGuangzhou 510006China

This paper introduces an improvement to electrochemical drilling process by coupling flow field and electric field in pulsating state. A novel tube with half-wedged shape at the end(HW-tube) is prepared, with both sidewall and wedged part of the HW-tube insulated. Only the flat part is utilized to provide electric field for electrochemical drilling. By rotating the HW-tube, both flow field and electric field in pulsating state are generated, alternating in different positions within the inter-electrode gap(IEG). The pulsating flow field enhances the mass transfer process, while pulsating electric field disperses material dissolution process and distribution of electrolytic byproducts. Both pulsating fields are coupled at the same frequency, further enhancing the electrochemical drilling process. Simulation results indicate that both flow field and electric field in pulsating state are generated. Compared to the traditional tube, the HW-tube significantly reduces the number of residual particles in IEG, and this number is further reduced by increasing the rotation speed. Experimental results reveal that the surface quality and dimensional uniformity of small hole are improved with HW-tube. With feed rate of 2.22 mm/min, a small hole with diameter of 1.52± 0.017 mm is drilled, resulting in a surface roughness of 0.331 μm.

关键词： Small holes Electrochemical drilling Tools Pulsating flow field Pulsating electric field

Estimation of surface geometry on combustion characteristics of AP/HTPB propellant under rapid depressurization

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Defence Technology（防务技术） 2024年第3期33卷 546-558页

作者： Kaixuan chen Zhenwei ye Xiaochun Xue Yonggang Yu School of Energy and Power Engineering Nanjing University of Science and TechnologyNanjing 210094JiangsuChina School of Science Hangzhou Dianzi UniversityHangzhou 310018ZhejiangChina

The 2D sandwich model serves as a potent tool in exploring the influence of surface geometry on the combustion attributes of Ammonium perchlorate/Hydroxyl-terminated polybutadiene(AP/HTPB)propellant under rapid pressure decay.The thickness of the sandwich propellant is derived from slicing the 3D random particle packing,an approach that enables a more effective examination of the micro-flame structure.Comparative analysis of the predicted burning characteristics has been performed with experimental studies.The findings demonstrate a reasonable agreement,thereby validating the precision and soundness of the model.Based on the typical rapid depressurization environment of solid rocket motor(initial combustion pressure is 3 MPa and the maximum depressurization rate is 1000 MPa/s).A-type(a flatter surface),B-type(AP recesses from the combustion surface),and C-type(AP protrudes from the combustion surface)propellant combustion processes are numerically simulated.Upon comparison of the evolution of gas-phase flame between 0.1 and 1 ms,it is discerned that the flame strength and form created by the three sandwich models differ significantly at the beginning stage of depressurization,with the flame structures gradually becoming harmonized over time.Conclusions are drawn by comparison extinction times:the surface geometry plays a pivotal role in the combustion process,with AP protrusion favoring combustion the most.

关键词： AP/HTPB propellant BDP model Rapid pressure decay Burning surface geometry

Ergothioneine and its congeners:anti-ageing mechanisms and pharmacophore

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Protein & Cell 2024年第3期15卷 191-206页

作者： Li chen Liping Zhang Xujun ye Zixin Deng Changming Zhao Department of Geriatrics Zhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China Key Laboratory of Combinatory Biosynthesis and Drug Discovery School of Pharmaceutical SciencesMinistry of EducationWuhan UniversityWuhan 430072China tThese authors contributed equally.

Ergothioneine,Ovothiol,and Selenoneine are sulfur/selenium-containing histidine-derived natural products widely distributed across different organisms.They exhibit significant antioxidant properties,making them as potential lead compounds for promoting health.Increasing evidence suggests that Ergothioneine is positively correlated with healthy ageing and longevity.The mechanisms underlying Ergothioneine's regulation of the ageing process at cellular and molecular levels are beginning to be understood.In this review,we provide an in-depth and extensive coverage of the anti-ageing studies on Ergothioneine and discuss its possible intracellular targeting pathways.In addition,we highlight the recent efforts in elucidating the biosynthetic details for Ergothioneine,Ovothiol,and Selenoneine,with a particular focus on the study of their pharmacophore-forming enzymology.

关键词： Ergothioneine antioxidant anti-ageing longevity biosynthesis enzymology