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Compound 3k治疗骨关节炎:调控氧化应激通路改善软骨细胞糖酵解的作用机制

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中国组织工程研究 2025年第2期29卷 363-370页

作者：郭素蓉曹士盛穆星彤杨青张娟天津医科大学口腔医学院天津市300041 天津医科大学口腔医院口腔修复科天津市300041

背景:骨关节炎现已被认为是一种代谢性疾病,既往研究表明糖酵解在骨关节炎的发生发展中起重要作用。Compound 3k作为一种新型糖酵解小分子抑制剂,具有抗炎及抗肿瘤等功效,因此可靶向糖酵解,有望为骨关节炎治疗提供新的思路。目的:基于... 详细信息

背景:骨关节炎现已被认为是一种代谢性疾病,既往研究表明糖酵解在骨关节炎的发生发展中起重要作用。Compound 3k作为一种新型糖酵解小分子抑制剂,具有抗炎及抗肿瘤等功效,因此可靶向糖酵解,有望为骨关节炎治疗提供新的思路。目的:基于缺氧诱导因子1α/活性氧的氧化应激通路探究Compound 3k在糖酵解过度活跃所导致的骨关节炎中的作用机制。方法:取对数生长期的ATDC5成软骨细胞,用10 ng/mL白细胞介素1β作用24 h诱导骨关节炎体外细胞模型,以CCK-8法检测不同浓度(0.25,0.5,1,2.5,5,10,15μmol/L)Compound 3k的细胞毒性,选出合适浓度进行后续实验。将软骨细胞随机分为对照组、模型组、治疗组,模型组以10 ng/mL的白细胞介素1β诱导,治疗组以Compound 3k预刺激2 h后与白细胞介素1β共培养,用CCK-8法检测各组细胞增殖情况;用ELISA试剂盒检测各组细胞炎症水平;用试剂盒检测各组细胞活性氧、细胞外乳酸脱氢酶及葡萄糖含量;qRT-PCR及Western blot检测相关炎症因子白细胞介素6、肿瘤坏死因子α及糖酵解相关基因葡萄糖转运蛋白1、甘油醛3-磷酸脱氢酶、单羧酸转运蛋白1和缺氧诱导因子1α的表达水平。结果与结论:①与对照组相比,模型组细胞增殖活性下降、糖酵解水平活跃,表现为细胞外乳酸脱氢酶含量增加(P<0.001),葡萄糖含量减少(P<0.001),相关炎症因子白细胞介素6(P<0.0001)及肿瘤坏死因子α(P<0.001),糖酵解相关基因葡萄糖转运蛋白1(P<0.001)、甘油醛3-磷酸脱氢酶(P<0.001)、单羧酸转运蛋白1(P<0.001)及缺氧诱导因子1α(P<0.001)的表达水平均上调,并伴随氧化应激,活性氧过量产生。②与模型组相比,Compound 3k的治疗有效提高细胞增殖活性,抑制过度活跃的糖酵解水平的同时,抑制了骨关节炎软骨细胞炎症(P<0.001)及糖酵解相关基因的表达(P<0.001),且抑制氧化应激,缺氧诱导因子1α的表达水平下调(P<0.0001),活性氧水平下降。③上述结果证实,Compound 3k抑制了白细胞介素1β诱导的软骨细胞炎症,其机制可能与糖酵解及缺氧诱导因子1α/活性氧介导的氧化应激有关。

关键词：骨关节炎糖酵解 Compound 3k 氧化应激 HIF-1α/ROS ATDC5细胞葡萄糖代谢白细胞介素1β 小分子药物

Diverse foraging strategies of breeding Swinhoe's Storm-petrel in the productive marginal sea of the Northwest Pacific

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Avian Research 2024年第1期15卷 27-34页

作者： Yachang Cheng Lei Zhu Lin Xue shisheng Ma Nan Jia Shaoping Zang Zhihai cao Jing Yuan Yang Liu State Key Laboratory of Biocontrol School of EcologySun Yat-sen UniversityShenzhen 518107China Guangxi Mangrove Research Center Guangxi Marine Academy of SciencesNanning 530021China Qingdao Bird Watch Society Qingdao 266121China Jiangsu Provincial Environmental Monitoring Center Nanjing 210019China Marine Science and Engineering Qingdao Agricultural UniversityQingdao 266109China Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering Fudan UniversityShanghai 200433China Qingdao Marine Management and Support Centre Qingdao 266555China Management Committee of Lingshan Island Provincial Nature Reserve Qingdao 266428China

Understanding the foraging behavior is essential for investigating seabird ecology and conservation,as well as monitoring the well-being of the marine environment.Breeding seabirds adopt diverse foraging strategies to maximize energy gains and cope with the intensified challenges of parenting and self-maintenance.Such tradeoff may stem from the heterogeneity of food resources and the constraints of central place foraging.Nevertheless,abundant marine productivity could alleviate the energy limitation for seabirds,resulting in a consistent foraging approach.Here,we investigated the foraging strategy during the breeding season of a cryptic small-sized seabird,Swinhoe’s Storm-petrel(Hydrobates monorhis),in the Yellow Sea,a productive marginal sea of the Northwest Pacific.Using GPS tracking,we evaluated habitat preference,quantified the foraging strategy,and tested if environmental conditions and individual traits influence foraging trips.We found that Swinhoe’s Storm-petrels preferred nearshore areas with shallow water and engaged in primarily short foraging trips.Distinctive southeastward and southwestward strategies emerged when combining trip metrics,including foraging direction,duration,and maximum distance.The bathymetry,proximity to the coastline,and sea surface temperature differed in two foraging strategies.Foraging strategies exhibited flexibility between individuals,potentially explained by wing morphology,in which longer-winged birds are more likely to embark on longer-distance foraging trips.These findings highlight the impact of environmental factors and individual traits on seabirds’foraging decisions in productive marginal sea ecosystems.Our study also provides valuable insights into the foraging ecology of this Asian endemic storm-petrel.

关键词： Behavioral strategy Biologging Central place foraging Marine primary productivity Seabird Sea surface temperature

Dysfunction of synaptic endocytic trafficking in Parkinson's disease

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Neural Regeneration Research 2024年第12期19卷 2649-2660页

作者： Xin Yi Ng Mian cao Programme in Neuroscience and Behavioural Disorders Duke-NUS Medical SchoolSingaporeSingapore Department of Physiology National University of SingaporeSingaporeSingapore

Parkinson's disease is characterized by the selective degeneration of dopamine neurons in the nigrostriatal pathway and dopamine deficiency in the striatum.The precise reasons behind the specific degeneration of these dopamine neurons remain largely elusive.Genetic investigations have identified over 20 causative PARK genes and 90 genomic risk loci associated with both familial and sporadic Parkinson's disease.Notably,several of these genes are linked to the synaptic vesicle recycling process,particularly the clathrinmediated endocytosis pathway.This suggests that impaired synaptic vesicle recycling might represent an early feature of Parkinson's disease,followed by axonal degeneration and the eventual loss of dopamine cell bodies in the midbrain via a"dying back"mechanism.Recently,several new animal and cellular models with Parkinson's disease-linked mutations affecting the endocytic pathway have been created and extensively characterized.These models faithfully recapitulate certain Parkinson's disease-like features at the animal,circuit,and cellular levels,and exhibit defects in synaptic membrane trafficking,further supporting the findings from human genetics and clinical studies.In this review,we will first summarize the cellular and molecular findings from the models of two Parkinson's disease-linked clathrin uncoating proteins:auxilin(DNAJC6/PARK19)and synaptojanin 1(SYNJ1/PARK20).The mouse models carrying these two PARK gene mutations phenocopy each other with specific dopamine terminal pathology and display a potent synergistic effect.Subsequently,we will delve into the involvement of several clathrin-mediated endocytosis-related proteins(GAK,endophilin A1,SAC2/INPP5 F,synaptotagmin-11),identified as Parkinson's disease risk factors through genome-wide association studies,in Parkinson's disease pathogenesis.We will also explore the direct or indirect roles of some common Parkinson's disease-linked proteins(alpha-synuclein(PARK1/4),Parkin(PARK2),and LRRK2(PARK8))in synaptic endocytic trafficking.Additionall

关键词： autophagy auxilin/PARK19 clathrin-mediated endocytosis dopamine neurons neurodegeneration nigrostriatal pathway Parkinson's disease synaptic vesicle recycling synaptojanin1/PARK20

Dynamic Setting Method of Assessment Indicators for Power Curves of Renewable Energy Sources Considering Scarcity of Reserve Resources

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Journal of Modern Power Systems and Clean Energy 2024年第1期12卷 101-114页

作者： Minghao cao Jilai Yu the Department of Electrical Engineering Harbin Institute of TechnologyHarbinChina

With the increasing proportion of renewable energy sources(RESs)in power grid,the reserve resource(RR)scarcity for correcting power deviation of RESs has become a potential issue.Consequently,the power curve of RES needs to be more rigorously assessed.The RR scarcity varies during different time periods,so the values of assessment indicators should be dynamically adjusted.The assessment indicators in this paper include two aspects,i.e.,deviation exemption ratio and penalty price.Firstly,this paper proposes a method for dynamically calculating the supply capacity and RR cost,primarily taking into account the operating status of thermal units,forecast information of RES,and load curve.Secondly,after clarifying the logical relationship between the degree of RR scarcity and the values of assessment indicators,this paper establishes a mapping function between them.Based on this mapping function,a dynamic setting method for assessment indicators is proposed.In the future,RES will generally be equipped with battery energy storage systems(BESSs).Reasonably utilizing BESSs to reduce the power deviation of RESs can increase the expected income of RESs.Therefore,this paper proposes a power curve optimization strategy for RESs considering self-owned BESSs.The case study demonstrates that the dynamic setting method of assessment indicators can increase the revenue of RESs while ensuring that the penalty fees paid by RESs to the grid are sufficient to cover the RR costs.Additionally,the power curve optimization strategy can help RESs further increase income and fully utilize BESSs to reduce power deviation.

关键词： Renewable energy battery energy storage system(BESS) power curve assessment reserve service parameter setting

Zeros of Complete Symmetric Polynomials over Finite Fields

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Journal of Systems Science & Complexity 2024年第4期37卷 1772-1788页

作者： cao Wei School of Mathematics and Statistics Minnan Normal University

Wan and Zhang(2021) obtained a nontrivial lower bound for the number of zeros of complete symmetric polynomials over finite fields, and proposed a problem whether their bound can be improved. In this paper, the author improves Wan-Zhang's bound from three aspects. The proposed results are based on the estimates related to the number of certain permutations and the value sets of non-permutation polynomials associated to the complete symmetric polynomial. And the author believes that there are still possibilities to improve the bounds and hence Wan-Zhang's bound.

关键词： Complete symmetric polynomial finite field permutation polynomial value set

Bioinspired Closed-loop CPG-based Control of a Robotic Manta for Autonomous Swimming

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Journal of Bionic Engineering 2024年第1期21卷 177-191页

作者： Yiwei Hao Yonghui cao Yingzhuo cao Xiong Mo Qiaogao Huang Lei Gong Guang Pan Yong cao School of Marine Science and Technology Northwestern Polytechnical UniversityXi'an 710072China Unmanned Vehicle Innovation Center Ningbo Institute of NPUNingbo 315103China Key Laboratory of Unmanned Underwater Vehicle Technology of Ministry of Industry and Information Technology Xi'an 710072China

Fish in nature exhibit a variety of swimming modes such as forward swimming,backward swimming,turning,pitching,etc.,enabling them to swim in complex scenes such as coral reefs.It is still difficult for a robotic fish to swim autonomously in a confined area as a real fish.Here,we develop an untethered robotic manta as an experimental platform,which consists of two flexible pectoral fins and a tail fin,with three infrared sensors installed on the front,left,and right sides of the head to sense the surrounding obstacles.To generate multiple swimming modes of the robotic manta and online switching of different modes,we design a closed-loop Central Pattern Generator(CPG)controller based on distance information and use a combination of phase difference and amplitude of the CPG model to achieve stable and rapid adjustment of yaw angle.To verify the autonomous swimming ability of the robotic manta in complex scenes,we design an experimental scenario with a concave obstacle.The experimental results show that the robotic manta can achieve forward swimming,backward swimming,in situ turning within the concave obstacle,and finally exit from the area safely while relying on the perception of external obstacles,which can provide insight into the autonomous exploration of complex scenes by the biomimetic robotic fish.Finally,the swimming ability of the robotic manta is verified by field tests.

关键词： Biomimetic robotic manta Central Pattern Generator Closed-loop control Backward swimming

Impacts of pancreatic exocrine insufficiency on gut microbiota

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 271-279页

作者： Yulin GUO Feng cao Fei LI Department of General Surgery Xuanwu Hospital of Capital Medical UniversityBeijing 100053China Acute Pancreatitis Clinical Center of Capital Medical University Beijing 100053China

Pancreatic exocrine insufficiency(PEI)can be induced by various kinds of diseases,including chronic pancreatitis,acute pancreatitis,and post-pancreatectomy.The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis,disorder of pancreatic fluid flow,and imbalance of secretion feedback.Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis,with the abundance of Lactobacillus and Bifidobacterium increasing the most,which could be partially reversed by pancreatic enzyme replacement therapy.Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota.Pancreatic exocrine secretions and changes in duodenal p H as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota.In turn,the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk.Going forward,more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

关键词： Pancreatic exocrine insufficiency Gut microbiota Gut microbiome Pancreatic enzyme replacement therapy

Deep learning sheds new light on non-orthogonal optical multiplexing

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Light(Science & Applications) 2024年第5期13卷 808-809页

作者： Zhengzhong Huang Liangcai cao Department of Precision Instruments Tsinghua UniversityBeijingChina

A deep neural network for non-orthogonal input channel encoding is proposed to recover speckle images through a multimode fiber.This novel approach could shed new light on the non-orthogonal optical multiplexing over ... 详细信息

关键词： optical multiplexing scattering

Angiogenesis in diseases:A half-century excursion from the initial therapeutic concept to current clinical benefits

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Chinese Medical Journal 2024年第6期137卷 636-637页

作者： Yihai cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholm 17177Sweden

Except a few tissues such as the cornea and cartilage that are avascular,blood vessels constitute a significant proportion of tissue masses in virtually all organs.Under physiological conditions,the adult vasculature remains quiescent to retain tissue and organ homeostatic functions.Too few or too many blood vessels are associated with the onset and progression of many diseases.In response to injuries,most tissues undergo repair by switching on angiogenesis,a key process of new blood vessel formation.^([1])Similarly,angiogenesis is often active in pathological tissues,including tumors and ischemic tissues to aggravate disease progression.

关键词： injuries organs diseases