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Peripheral and central control of obesity by primary cilia

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Journal of Genetics and Genomics 2023年第5期50卷 295-304页

作者： Yue Wu Jun Zhou yunfan yang Center for Cell Structure and Function Shandong Provincial Key Laboratory of Animal Resistance BiologyCollaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinanShandong 250014China State Key Laboratory of Medicinal Chemical Biology Haihe Laboratory of Cell EcosystemCollege of Life SciencesNankai UniversityTianjin 300071China Department of Cell Biology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong 250012China

Primary cilia are hair-like structures that protrude from the cell *** are capable of sensing external cues and conveying a vast array of signals into cells to regulate a variety of physiological *** in cilium-associated genes are linked to a group of diseases with overlapping clinical manifestations,collectively known as ciliopathies.A significant proportion of human ciliopathy cases are accompanied by metabolic disorders such as obesity and type 2 ***,the mechanisms through which dysfunction of primary cilia contributes to obesity are *** this review,we present an overview of primary cilia and highlight obesity-related *** also discuss the potential role of primary cilia in peripheral organs,with a focus on adipose *** addition,we emphasize the significance of primary cilia in the central regulation of obesity,especially the involvement of ciliary signaling in the hypothalamic control of feeding *** review therefore proposes a framework of both peripheral and central regulation of obesity by primary cilia,which may benefit further exploration of the ciliary role in metabolic regulation.

关键词： Ciliopathy Metabolism Adipose tissue Adipogenesis Hypothalamus

On the Polygonal Wear Evolution of Heavy-Haul Locomotive Wheels due to Wheel/Rail Flexibility and Its Mitigation Measures

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Chinese Journal of Mechanical Engineering 2024年第1期37卷 40-61页

作者： yunfan yang Feifan Chai Pengfei Liu Liang Ling Kaiyun Wang Wanming Zhai State Key Laboratory of Mechanical Behavior and System Safety of Traffic Engineering Structures Shijiazhuang Tiedao UniversityShijiazhuang 050043China State Key Laboratory of Rail Transit Vehicle System Southwest Jiaotong UniversityChengdu 610031China

Wheel polygonal wear can immensely worsen wheel/rail interactions and vibration performances of the train and track,and ultimately,lead to the shortening of service life of railway *** present,wheel/rail medium-or high-frequency frictional interactions are perceived as an essential reason of the high-order polygonal wear of railway wheels,which are potentially resulted by the flexible deformations of the train/track system or other external *** this work,the effect of wheel/rail flexibility on polygonal wear evolution of heavy-haul locomotive wheels is explored with aid of the long-term wheel polygonal wear evolution simulations,in which different flexible modeling of the heavy-haul wheel/rail coupled system is ***,the mitigation measures for the polygonal wear of heavy-haul locomotive wheels are *** results point out that the evolution of polygonal wear of heavy-haul locomotive wheels can be veritably simulated with consideration of the flexible effect of both wheelset and *** of mixed-line operation of heavy-haul trains and application of multicut wheel re-profiling can effectively reduce the development of wheel polygonal *** research can provide a deep-going understanding of polygonal wear evolution mechanism of heavy-haul locomotive wheels and its mitigation measures.

关键词： Heavy-haul locomotive Wheel polygonal wear Wheel/rail flexibility Long-term polygonal wear evolution Mitigation measures

Quantitative detection of locomotive wheel polygonization under non-stationary conditions by adaptive chirp mode decomposition

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Railway Engineering Science 2022年第2期30卷 129-147页

作者： Shiqian Chen Kaiyun Wang Ziwei Zhou yunfan yang Zaigang Chen Wanming Zhai Train and Track Research Institute State Key Laboratory of Traction PowerSouthwest Jiaotong UniversityChengdu 610031China

Wheel polygonal wear is a common and severe defect,which seriously threatens the running safety and reliability of a railway vehicle especially a *** to non-stationary running conditions(e.g.,traction and braking)of the locomotive,the passing frequencies of a polygonal wheel will exhibit time-varying behaviors,which makes it too difficult to effectively detect the wheel ***,most existing methods only achieve qualitative fault diagnosis and they cannot accurately identify defect *** address these issues,this paper reports a novel quantitative method for fault detection of wheel polygonization under non-stationary conditions based on a recently proposed adaptive chirp mode decomposition(ACMD)***,a coarse-to-fine method based on the time–frequency ridge detection and ACMD is developed to accurately estimate a time-varying gear meshing frequency and thus obtain a wheel rotating frequency from a vibration acceleration signal of a *** the rotating frequency is obtained,signal resampling and order analysis techniques are applied to an acceleration signal of an axle box to identify harmonic orders related to polygonal ***,the ACMD is combined with an inertial algorithm to estimate polygonal wear *** only a dynamics simulation but a field test was carried out to show that the proposed method can effectively detect both harmonic orders and their amplitudes of the wheel polygonization under non-stationary conditions.

关键词： Wheel polygonal wear Fault diagnosis Nonstationary condition Adaptive mode decomposition Time–frequency analysis

High-Quality and Wafer-Scale Cubic Silicon Carbide Single Crystals

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Energy & Environmental Materials 2024年第4期7卷 442-449页

作者： Guobin Wang Da Sheng yunfan yang Hui Li Congcong Chai Zhenkai Xie Wenjun Wang Jiangang Guo Xiaolong Chen Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Cubic silicon carbide(3C-SiC)has superior mobility and thermal conduction over that of widely applied hexagonal ***,much lower concentration of interfacial traps between insulating oxide gate and 3C-SiC helps fabricate reliable and long-life devices like metal-oxidesemiconductor field effect ***,the growth of high-quality and wafer-scale 3C-SiC crystals has remained a big challenge up to now despite decades-long efforts by researchers because of its easy transformation into other polytypes during growth,limiting the development of 3C-SiC-based ***,we report that 3C-SiC can be made thermodynamically favored from nucleation to growth on a 4H-SiC substrate by top-seeded solution growth technique,beyond what is expected by classical nucleation *** enables the steady growth of high-quality and large-size 3C-SiC crystals(2-4-inch in diameter and 4.0-10.0 mm in thickness)*** as-grown 3C-SiC crystals are free of other polytypes and have high-crystalline *** findings broaden the mechanism of hetero-seed crystal growth and provide a feasible route to mass production of 3C-SiC crystals,offering new opportunities to develop power electronic devices potentially with better performances than those based on 4H-SiC.

关键词： cubic SiC high-temperature solution growth high-temperature surface tension solid-liquid interfacial energy wide band gap semiconductor

The tumor suppressor CYLD controls epithelial morphogenesis and homeostasis by regulating mitotic spindle behavior and adherens junction assembly

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Journal of Genetics and Genomics 2017年第7期44卷 343-353页

作者： Wei Xie yunfan yang Siqi Gao Ting Song Yuhan Wu Dengwen Li Min Liu Jun Zhou Key Laboratory ofAnimal Resistance Biology ofShandong Province Institute of Biomedical SciencesCollege ofLife Sciences.Shandong Normal University Jinun 250014China State Key Laboratory ofMedicinal Chemical Biology College of life SciencesNankai UniversityTianjin 300071China

Epithelial morphogenesis and homeostasis are essential for animal development and tissue regeneration, and epithelial disorganization is associated with developmental disorders and tumorigenesis. However, the molecular mechanisms that contribute to the morphogenesis and homeostasis of the epithelium remain elusive. Herein, we report a novel role for the cylindromatosis （CYLD） tumor suppressor in these events. Our results show that CYLD depletion disrupts epithelial organization in both Drosophila egg chambers and mouse skin and intestinal epithelia. Microscopic analysis of proliferating cells in mouse epithelial tissues and cultured organoids reveals that loss of CYLD synergizes with tumor-promoting agents to cause the misorientation of the mitotic spindle. Mechanistic studies show that CYLD accu- mulates at the cell cortex in epithelial tissues and cultured ceils, where it promotes the formation of epithelial adherens junctions through the modulation of microtuhule dynamics. These data suggest that CYLD controls epithelial morphogenesis and homeostasis by modulating the assembly of adherens junctions and ensuring proper orientation of the mitotic spindle. Our findings thus provide novel insight into the role of CYLD in development, tissue homeostasis, and tumorigenesis.

关键词： Epithelium CYLD Mitotic spindle Cell cortex Adherens junction

Investigation and mitigation of Mott neuronal oscillation fluctuation in spiking neural network

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Science China(Information Sciences) 2024年第2期67卷 291-301页

作者： Lindong WU Zongwei WANG Lin BAO Linbo SHAN Zhizhen YU yunfan yang Shuangjie ZHANG Guandong BAI Cuimei WANG John ROBERTSON Yuan WANG Yimao CAI Ru HUANG School of Integrated Circuits Peking University Beijing Advanced Innovation Center for Integrated Circuits State Key Laboratory of Information Photonics and Optical Communications Beijing University of Posts and Telecommunications Department of Engineering University of Cambridge

Mott devices, featuring low hardware cost and high energy efficiency, have been demonstrated as a key oscillatory element in artificial neurons to enable spiking neural networks(SNNs) such as conversionbased SNNs(CSNNs). However, there will be inevitably non-ideal fluctuation in the oscillation behavior,causing the accuracy degradation of networks. In this paper, we investigate the Mott neuronal oscillation fluctuation(NOF) through experiments and modeling. The results show that the NOF phenomenon conforms to Gaussian distribution and originates from thermal fluctuation induced switching voltage variations. We construct a two-layer CSNN for image recognition tasks to study the NOF effect and propose the activation function boundary(AFB) method to strengthen the stability of the network. The results indicate that AFB can improve the accuracy of CSNN by up to 15.5% by tightening output distribution.

关键词： Mott neuron oscillation fluctuation variation-aware Mott neuronal model conversion-based spiking neural network activation function boundary

Theoretical investigation on the fluorescent sensing mechanism for recognizing formaldehyde: TDDFT calculation and excited-state nonadiabatic dynamics

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Chinese Physics B 2023年第5期32卷 674-681页

作者：杨云帆杨璐佳马凤才李永庆邱岳 Key Laboratory for Microstructural Material Physics of Hebei Province School of ScienceYanshan UniversityQinhuangdao 066004China Department of Physics Liaoning UniversityShenyang 110036China State Key Laboratory of Molecular Reaction Dynamics Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Grimwade Centre for Cultural Materials Conservation School of Historical and Philosophical StudiesFaculty of Arts University of MelbourneParkvilleVIC 3052Australia

Inspired by the activity-based sensing method, the hydrazine-modified naphthalene derivative(Naph1) was synthesized and used as a fluorescent probe to detect formaldehyde(FA) in living cells. Through the condensation reaction between the probe Naph1 and analyte FA, researchers observed a ~14 folds enhancement of fluorescent signal around 510 nm in an experiment, realizing the high selectivity and sensitivity detection of FA. However, a theoretical understanding of the sensing mechanism was not provided in the experimental work. Given this, the light-up fluorescent detecting mechanism was in-depth unveiled by performing the time-dependent density functional theory(TDDFT) and the complete active space self-consistent field(CASSCF) theoretical calculations on excited-state intramolecular proton transfer(ESIPT)and non-adiabatic excited-state dynamics simulation. The deactivation channel of S_1/T_2 intersystem crossing(ISC) was turned off to successfully recognize FA. Insight into the ESIPT-based fluorescent detecting mechanism indicated that ESIPT was essential to light-up fluorescent probes. This work would provide a new viewpoint to develop ESIPT-based fluorescent probes for detecting reactive carbon species in vivo or vitio.

关键词： proton transfer twisting intramolecular charge transfer intersystem crossing fluorescent probe

HDAC I/IIb selective inhibitor Purinostat Mesylate combined with GLS1 inhibition effectively eliminates CML stem cells

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Bioactive Materials 2023年第3期21卷 483-498页

作者： Qiang Qiu Linyu yang Yunyu Feng Zejiang Zhu Ning Li Li Zheng Yuanyuan Sun Cong Pan Huandi Qiu Xue Cui Wei He Fang Wang Yuyao Yi Minghai Tang Zhuang yang yunfan yang Zhihui Li Lijuan Chen Yiguo Hu State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengduPR China Thyroid and Parathyroid Surgery Center State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduPR China Department of Hematology and Research Laboratory of Hematology West China HospitalSichuan UniversityChengduPR China Center of Infectious Diseases West China HospitalSichuan UniversityChengduPR China Guizhou Normal College GuiyangPR China

Purinostat Mesylate(PM)is a novel highly selective and active HDAC I/IIb inhibitor,and the injectable formulation of PM(PMF)based on the compound prescription containing cyclodextrin completely can overcome PM’s poor solubility and improves its stability and pharmacokinetic ***,we showed that PM effectively repressed the survival of Ph+leukemia cells and CD34+leukemia cells from CML patients in *** vivo studies demonstrated that PMF significantly prevented BCR-ABL(T315I)induced CML progression by restraining leukemia stem cells(LSCs),which are insensitive to chemotherapy and responsible for CML *** studies revealed that targeting HDAC I/IIb repressed several important factors for LSCs survival including c-Myc,β-Catenin,E2f,Ezh2,Alox5,and mTOR,as well as interrupted some critical biologic ***,PMF increased glutamate metabolism in LSCs by increasing *** combination of PMF and glutaminase inhibitor BPTES synergistically eradicated LSCs by altering multiple key proteins and signaling pathways which are critical for LSC survival and ***,our findings represent a new therapeutic strategy for eliminating LSCs by targeting HDAC I/IIb and glutaminolysis,which potentially provides a guidance for PMF clinical trials in the future for TKI resistance CML patients.

关键词： Chronic myelogenous leukemia Leukemia stem cell Selective HDAC I/IIb inhibitor GLS1 Mouse model

Effect of gauge corner lubrication on wheel/rail non-Hertzian contact and rail surface damage on the curves

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Acta Mechanica Sinica 2022年第3期38卷 132-148,I0004页

作者： yunfan yang Xinru Guo Liang Ling Kaiyun Wang Witnming Zhai State Key Laboratory of Traction Power Southwest Jiaotong UniversityChengdu 610031China

Wheel/rail rolling contact is a highly nonlinear issue affected by the complicated operating environment(including adhesion conditions and motion attitude of train and track system),which is a fundamental topic for further insight into wheel/rail tread wear and rolling contact fatigue(RCF).The rail gauge corner lubrication(RGCL)devices have been installed on the metro outer rail to mitigate its wear on the curved *** paper presents an investigation into the influence ofRGCL on wheel/rail nonHertzian contact and rail surface RCF on the curves through numerical *** this end,a metro vehicle-slab track interaction dynamics model is extended,in which an accurate wheel/rail non-Hertzian contact algorithm is *** influence of RGCL on wheel/rail creep,contact stress and adhesion-slip distributions and fatigue damage of rail surface are *** simulation results show that RGCL can markedly affect wheel/rail contact on the tight *** is further suggested that RGCL can reduce rail surface RCF on tight curves through the wheel/rail low-friction interactions.

关键词： Metro Gauge corner lubrication Wheel/rail non-Hertzian contact theory Contact stress Rail surface RCF