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MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis

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Journal of Molecular Cell Biology 2019年第9期11卷 747-760页

作者： Yunxia Zhu Yi Sun Yuncai Zhou Yan Zhang Tao Zhang Yating Li Weiyan You Xiaoai Chang Li Yuan Xiao Han Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing 210029China

Current research indicates that beta cell loss in type 2 diabetes may be attributed to beta cell dedifferentiation rather than apoptosis;however,the mechanisms by which this occurs remain poorly understood.Our previous study demonstrated that elevation of microRNA-24(miR-24)in a diabetic setting caused beta cell dysfunction and replicative deficiency.In this study,we focused on the role of miR-24 in beta cell apoptosis and dedifferentiation under endoplasmic reticulum(er)stress conditions.We found that miR-24 overabundance protected beta cells from thapsigargin-induced apoptosis at the cost of accelerating the impairment of glucosestimulated insulin secretion(GSIS)and enhancing the presence of dedifferentiation markers.Ingenuity?Pathway Analysis(IPA)revealed that elevation of miR-24 had an inhibitory effect on XBP1 and ATF4,which are downstream effectors of two key branches of er stress,by inhibiting its direct target,Irela.Notably,elevated miR-24 initiated another pathway that targeted Mafa and decreased GSIS function in surviving beta cells,thus guiding their dedifferentiation under er stress conditions.Our results demonstrated that the elevated miR-24,to the utmost extent,preserves beta cell mass by inhibiting apoptosis and inducing dedifFerentiation.This study not only provides a novel mechanism by which miR-24 dominates beta cell turnover under persistent metabolic stress but also offers a therapeutic consideration for treating diabetes by inducing dedifferentiated beta cells to re-differentiation.

关键词： microRNA-24 er stress apoptosis dedifferentiation type 2 diabetes pancreatic beta cells

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Three-dimensional ATUM-SEM reconstruction and analysis of hepatic endoplasmic reticulum-organelle interactions

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Journal of Molecular Cell Biology 2021年第9期13卷 636-645页

作者： Yi Jiang Linlin Li Xi Chen Jiazheng Liu Jingbin Yuan Qiwei Xie Hua Han National Laboratory of Pattern Recognition Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 101408China School of Future Technology University of Chinese Academy of SciencesBeijing 101408China Data Mining Lab Beijing University of TechnologyBeijing 100124China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China

The endoplasmic reticulum(er)is a contiguous and complicated membrane network in eukaryotic cells,and membrane contact sites(MCSs)between the er and other organelles perform vital cellular functions,including lipid homeostasis,metabolite exchange,calcium level regulation,and organelle division.Here,we establish a whole pipeline to reconstruct all er,mitochondria,lipid droplets,lysosomes,peroxisomes,and nuclei by automated tape-collecting ultramicrotome scanning electron microscopy and deep learning techniques,which generates an unprecedented 3D model for mapping liver samples.Furthermore,the morphology of various organelles and the MCSs between the er and other organelles are systematically analyzed.We found that the er presents with predominantly flat cisternae and is knitted tightly all throughout the intracellular space and around other organelles.In addition,the er has a smaller volume-to-membrane surface area ratio than other organelles,which suggests that the er could be more suited for functions that require a large membrane surface area.Our data also indicate that er-mitochondria contacts are particularly abundant,especially for branched mitochondria.Our study provides 3D reconstructions of various organelles in liver samples together with important fundamental information for biochemical and functional studies in the liver.

关键词： 3D reconstruction ATUM-SEM deep learning liver er MCSs

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Luminescence Properties and Crystal Growth of er/Yb Codoped KGd(WO_4)_2

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Chinese Journal of Structural Chemistry 2005年第8期24卷 879-884页

作者： WANG Yan TU Chao-Yang ZHU Zhao-Jie LI Jian-Fu YOU Zhen-Yu WU Bai-Chang State Key Laboratory of Structural Chemistry Fujian Institute of Research on theStructure of Matter The Chinese Academy of Sciences ChinaFuzhou Fujian 350002

In this paper, the spectral and luminescence properties of a series of KGd（WO4）2 powder samples codoped with different concentrations of er^3＋ and Yb^3＋ were reported,and the best doping concentrations were found to be lat% er^3＋ and 10at% Yb^3＋ for attaining the strongest intensity. The er^3＋/yb^3＋ codoped KGd（WO4）2 crystal with good optical quality was grown by the TSSG method and the growth conditions were presented. The unpolarized absorption and emission spectra of the crystal have been measured. The strong absorption peak is at 980 nm with a FWHM of 65 nm, and the emission peak is at 1536 nm when pumped by 976 rim. The fluorescence lifetime of manifold ^4I13/2 is estimated to be 4.5 ms at room temperature.Investigations of er, Yb：KGW crystal have shown it to have necessary combination of properties to get an effective generation of - 1.54 μm eye-safe radiation with laser diode pumping.

关键词： er Yb：KGW crystal luminescence properties,crystal growth optical properties

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Poly-PR in C9ORF72-Related Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Causes Neurotoxicity by Clathrin-Dependent Endocytosis

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Neuroscience Bulletin 2019年第5期35卷 889-900页

作者： Rui Wang Xingyun Xu Zongbing Hao Shun Zhang Dan Wu Hongyang Sun Chenchen Mu Haigang Ren Guanghui Wang Laboratory of Molecular Neuropathology Jiangsu Key Laboratory of Neuropsychiatric Diseases and Department of Pharmacology College of Pharmaceutical SciencesSoochow University

GGGGCC repeat expansions in the C9 ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia(c9 ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9 ORF72 produce five dipeptide repeat(DPR) proteins by an unconventional repeat-associated non-ATG(RAN)translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs(poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5 Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase(JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PRinduced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependentendocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides.

关键词： Amyotrophic lateral sclerosis C9ORF72 Poly-PR Clathrin er stress

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Widely tunable passively Q-switched er3+-doped ZrF4 fiber laser in the range of 3.4–3.7 μm based on a Fe2+:ZnSe crystal

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Photonics Research 2019年第9期7卷 1106-1111页

作者： HONGYU LUO JIAN YANG JIANFENG LI YONG LIU State Key Laboratory of Electronic Thin Films and Integrated Devices School of Optoelectronic Science and EngineeringUniversity of Electronic Science and Technology of China (UESTC)

We report the first(to the best of our knowledge) tunable passively Q-switched er3+-doped ZrF4 fiber laser around 3.5 μm. In this case, a Fe2+:ZnSe crystal is used as the saturable absorber, and a plane-ruled grating in a Littrow configuration acts as the tuning element. At the tuned wavelength of 3478.0 nm, stable Q-switching with a maximum average power of 583.7 mW was achieved with a slope efficiency of 15.2% relative to the launched 1981 nm pump power. Further power scaling is mainly limited by the available 1981 nm pump power. The corresponding pulse width, repetition rate, and pulse energy are 1.18 μs, 71.43 kHz, and 7.54 μJ, respectively. By rotating the grating, the Q-switching can be continuously tuned in the region of 3.4–3.7 μm. To the best of our knowledge, this is the first pulsed rare-earth-doped fiber laser tunable in the region beyond 3.4 μm.

关键词： CW ZnSe crystal doped ZrF4 fiber laser in the range of 3.4 m based on a Fe Widely tunable passively Q-switched er

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Microstructure and performance of AZ80D magnesium alloy by purification of chloride flux containing er

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Rare Metals 2014年第5期33卷 541-546页

作者： Zhong-Jun Wang Guan-Qiao Su Wei-Ping Jia Qing-Xiang Yang School of Material and Metallurgy University of Science and Technology Liaoning Key Laboratory of Materials Forming and Microstructure and Properties Control Education Department in Liaoning Province State Key Laboratory of Metastable Materials Science and Technology College of Materials Science and EngineeringYanshan University

The purification effects of er addition in chloride flux during smelting on microstructure, tensile properties, and corrosion resistance of as-cast AZ80 D magnesium alloy were carried out. The results show that er addition in the flux can eliminate the MgO inclusions and improve the tensile properties and corrosion resistance of the alloy. Using chloride flux mixed with 8.0 wt% er, σb and δ of the as-cast AZ80 D magnesium alloy can be improved from 150 MPa and 2.1 % to the maximum value of 230 MPa and 4.8 %, respectively. Meanwhile, the corrosion rate decreases from 1.10 to 0.12 mg·（cm^2·d）^-1 in 5 wt% NaCl solution. However, with increasing er content in chloride flux further, φ-（Al7erMn5） and τ-（Al66.7Mg23.3er10） phase are formed, and the morphology of γ-（Mg17Al12） phase is modified. The coarse φ-（Al7erMn5）phase along dendrite boundaries decreases cohesion force between dendrites, which results in the worse of tensile properties.

关键词： er Chloride flux AZ80D Microstructure Magnesium alloy

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The Role of Endoplasmic Reticulum Stress-related Apoptosis in Vascular Endothelium Pathogenesis

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Biomedical and Environmental Sciences 2018年第7期31卷 555-559页

作者： TAO Yong Kang SHI Jing YU Pu Lin ZHANG Guo Qiang Departments of Emergency China-Japan Friendship Hospital Department of Deriatric Medicine Beijing Hospital National Center of Gerontology

Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.

关键词： er UPR GRP The Role of Endoplasmic Reticulum Stress-related Apoptosis in Vascular Endothelium Pathogenesis HUVECs

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Modification Effect of er on Hypoeutectic Al-8Si Alloy

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Journal of Rare Earths 2005年第S1期23卷 474-477页

作者：韩娜边秀房尹奎波姚秀军 Key Laboratory of Liquid Structure and Heredity of Materials Ministry of Education Shandong University Jinan 250061 China

The modification effect of er on hypoeutectic Al-8Si alloy was investigated by KH-2200 optical microscope, JXA-8800R electron probe microanalysis (EPMA) and CMT5105 electromechanical universal testing machine. The results show that the eutectic silicon is modified from a coarse flake-like to refined plate-like structure and the tensile properties are improved. With the additional level of er up to 0.5%, the tensile strength of the Al-8Si alloy is increased by 24%. The Al-8Si-0.5er alloy has a ductile fractured surface, while the unmodified Al-8Si alloy possesses a brittle fractured surface.

关键词： Al-8Si er modification tensile properties

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Synergistic Balance of Strength and Corrosion Resistance in Al-Mg-er Alloys

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Acta Metallurgica Sinica(English Letters) 2020年第5期33卷 659-670页

作者： Haifei Zhou Zhouhai Qian Mengcheng Zhou Xuebing Liu Yong Li Xinfang Zhang Zhejing Electric Power Corporation Research Institute Hangzhou 310014China State Key Laboratory of Advanced Metallurgy School of Metallurgical and Ecological EngineeringUniversity of Science and Technology BeijingBeijing 100083China

High-strength,corrosion-resistant,and lightweight Al-Mg alloys perform an important function in harsh coastal service environments.Corrosion resistance is generally inversely correlated with strength;hence,it is difficult to simultaneously optimize both.In this study,a low-magnesium er-containing Al-based alloy that is stronger and more corrosion resistant than Al-based alloys have been reported.The alloy contains er,and the precipitation of Al3 er within a face-centered cubic matrix is obtained by a series of smelting-casting,heat treatment,and rolling processes.It is presumed that the strengthening phase of Al3 er pinning dislocations improves alloy strength.It also increases the recrystallization temperature of cold-rolled matrix and induces the distribution of small-angle grain boundaries,thus allowing the alloy to achieve excellent environmental corrosion resistance.As a result,strength and corrosion resistance are simultaneously improved.

关键词： Al-Mg alloy Al3er Strength Corrosion resistance er

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X-RAY POWDer DIFFRACTION DATA AND STRUCTURAL REFINEMENT OF er₃Co₆Sn₅

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中国有色金属学会会刊：英文版 1999年第1期9卷 88-90页

作者： He, Wei Zeng, Lingmin Qin, Wen Yan, Jialin Hao, Jianmin Univ of Science and Technology of China Hefei China

１ＩＮＴＲＯＤＵＣＴＩＯＮＲａｒｅｍｅｔａｌｓａｎｄｔｈｅｉｒｃｏｍｐｏｕｎｄｓｈａｖｅｏｕｔｓｔａｎｄｉｎｇｐｒｏｐｅｒｔｉｅｓａｎｄａｒｅｐａｉｄｉｎｃｒｅａｓｉｎｇａｔｅｎｔｉｏｎｔｏ．Ｎｕｍｅｒｏｕｓｉｎ... 详细信息

１ＩＮＴＲＯＤＵＣＴＩＯＮＲａｒｅｍｅｔａｌｓａｎｄｔｈｅｉｒｃｏｍｐｏｕｎｄｓｈａｖｅｏｕｔｓｔａｎｄｉｎｇｐｒｏｐｅｒｔｉｅｓａｎｄａｒｅｐａｉｄｉｎｃｒｅａｓｉｎｇａｔｅｎｔｉｏｎｔｏ．Ｎｕｍｅｒｏｕｓｉｎｖｅｓｔｉｇａｔｉｏｎｓｉｎｔｈｅ...

关键词： er 3Co 6Sn 5 X ray powder diffraction Rietveld structural refinement

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