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Artificial Nucleic Acid Tractor-Directed Simultaneous Depletion of Oncogenic Membrane Proteins Without Hijacking Proteolysis-Specific Actuator

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CCS Chemistry 2024年第2期6卷 439-449页

作者： Zhen Zou Songlan Pan Qian Xue Ting Chen Ziyun Huang Bei Qing Pengfei liu Conghui Zhao Yunlin Sun Erhu Xiong Ronghua Yang Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research Ministry of EducationCollege of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha 410081 School of Chemistry and Chemical Engineering Hunan Provincial Key Laboratory of CytochemistryChangsha University of Science and TechnologyChangsha 410114 The Second Xiangya Hospital Central South UniversityChangsha 410011

Targeted protein degradation(TPD)is an emerging tool for degrading proteins of interest,which affords an attractive modality for cancer therapy.However,the present TPD technologies must engage a proteolysis-specific actuator to initiate degradation of targeted proteins in the proteasome or lysosome.Herein,we report an artificial tractor that can induce endocytosis-mediated protein depletion without hijacking a proteolysis-specific actuator.In this design,bispecific aptamer chimeras(BSACs)are established,which can bridge human epidermal growth factor receptor 2(ErbB-2),an important biomarker in a common important biomarker in cancer,with membrane proteins of interest.Taking advantage of the property of aptamer-induced endocytosis and digestion of ErbB-2,another membrane protein is translocated into the lysosome in a hitchhike-like manner,resulting in lysosomal proteolysis along with ErbB-2.This strategy frees the TPD from the fundamental limitation of proteolysis-specific actuator and allows simultaneous regulation of the quantity and function of two oncogenic receptors in a cell-type-specific manner,expanding the application scope of TPD-based therapeutics.

关键词： targeted protein degradation aptamer epidermal growth factor receptor 2 lysosome membrane proteins cancer therapy

Robust autofocusing propagation in turbulence

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Chinese Physics B 2024年第6期33卷 370-375页

作者：刘娜娜谭柳陈凯健洪佩龙莫小明邹炳锁任煜轩梁毅 Guangxi Key Laboratory for Relativistic Astrophysics Center on Nanoenergy ResearchSchool of Physical Science and TechnologyGuangxi UniversityNanning 530004China School of Mathematics and Physics Anqing Normal UniversityAnqing 246133China Institute for Translational Brain Research MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China

Turbulence in complex environments such as the atmosphere and biological media has always been a great challenge to the application of beam propagation in optical communication, optical trapping and manipulation. To overcome this challenge, this study comprehensively investigates the robust propagation of traditional Gaussian and autofocusing beams in turbulent environments. In order to select stable beams that exhibit high intensity and high field gradient at the focal position in complex environments, Kolmogorov turbulence theory is used to simulate the propagation of beams in atmospheric turbulence based on the multi-phase screen method. We systematically analyze the intensity fluctuations, the variation of the coherence factor and the change in the scintillation index with propagation distance. The analysis reveals that the intensity fluctuations of autofocusing beams are significantly smaller than those of Gaussian beams, and the coherence of autofocusing beams is better than that of Gaussian beams under turbulence. Moreover, autofocusing beams exhibit less oscillation than Gaussian beams, indicating that autofocusing beams propagate in complex environments with less distortion and intensity fluctuation. Overall, this work clearly demonstrates that autofocusing beams exhibit higher stability in propagation compared with Gaussian beams, showing great promise for applications such as optical trapping and manipulation in complex environments.

关键词： propagation beams autofocusing turbulence

A bacterial protein Rhp-PSP inhibits plant viral proliferation through endoribonuclease activity

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Journal of Integrative Agriculture 2024年第6期23卷 1967-1978页

作者： Lijie Chen Qianze Peng Xiaohua Du Weixing Zhang Ju’e Cheng Shu’e Sun Deyong Zhang Pin Su Yong liu Longping Branch College of BiologyHunan UniversityChangsha 410082China State Key Laboratory of Hybrid Rice/Institute of Plant Protection Hunan Academy of Agricultural SciencesChangsha 410125China

Plant virus causes massive crop losses globally.However,there is currently no effective measure to control plant viral disease.Previously,we identify an antiviral protein Rhp-PSP,produced by the bacterial Rhodopseudomonas palustris strain JSC-3b.In this study,we discover that the antiviral activity of Rhp-PSP relies on its endoribonuclease activity.Converting the arginine(R)residue at position 129 onto alanine(A)abolishs its endoribonuclease activity on coat protein(CP)RNA of tobacco mosaic virus(TMV),consequentially,compromises the antiviral activity of Rhp-PSP.Further investigation demonstrates that,the mutant Rhp-PSP^(R129A)is unable to form the homotrimer as the wild type,indicating the importance of quaternary junction for the endoribonuclease activity.Overexpression of Rhp-PSP in Nicotiana benthamiana significantly enhances the resistance against TMV of seedlings,while expression of Rhp-PSP^(R129A)did not,confirming that endoribonuclease activity is responsible for the antiviral activity of Rhp-PSP.In addition,foliar spray of Rhp-PSP solution on tomato and pepper plants significantly reduces the disease index of viral diseases,indicating that Rhp-PSP shows potential to develop antiviral agent in practice.

关键词： Rhodopseudomonas palustris Rhp-PSP tobacco mosaic virus endoribonuclease antiviral activity

Design and commissioning of a wideband RF system for CSNS-Ⅱ rapid-cycling synchrotron

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Nuclear Science and Techniques 2024年第1期35卷 35-44页

作者： Jian Wu Xiang Li Bin Wu Chun-Lin Zhang Yang liu Wei Long Xiao Li University of Chinese Academy of Sciences Beijing 100049China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Spallation Neutron Source Science Center Dongguan 523803China

The China Spallation Neutron Source(CSNS) upgrade project(CSNS-Ⅱ) aims to enhance the beam power from 100 to 500 kW. A dual-harmonic accelerating method has been adopted to alleviate the stronger space-charge effect in rapid-cycling synchrotrons owing to the increased beam intensity. To satisfy the requirements of dual-harmonic acceleration, a new radiofrequency(RF) system based on a magnetic alloy-loaded cavity is proposed. This paper presents design considerations and experimental results regarding the performance evaluation of the proposed RF system through high-power tests and beam commissioning. The test results demonstrate that the RF system satisfies the desired specifications and affords significant benefits for CSNS-Ⅱ.

关键词： Dual-harmonic acceleration Magnetic alloy-loaded cavity RF system

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a

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World Journal of Stem Cells 2024年第2期16卷 191-206页

作者： Fan Yang Wan-Qi Xiong Chen-Zhi Li Ming-Jian Wu Xiu-Zhi Zhang Chun-Xiao Ran Zhen-Hao Li Yan Cui Bao-Yi liu De-Wei Zhao Department of Orthopedics Affiliated Zhongshan Hospital of Dalian UniversityDalian 116001Liaoning ProvinceChina

BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and biomechanics.Factors like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA development.Early-stage treatment options primarily target symptom relief.Mesenchymal stem cells(MSCs)show promise for treatment,despite challenges.Recent research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA progression.This suggests exosomes(Exos)as a promising avenue for future treatment.While these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is essential.AIM To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat models.METHODS Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle suspension.The three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of arthritis.RESULTS General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control group.Additionally,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the normal extracellular vesicle group.Imaging examinat

关键词： Exosomes Osteoarthritis Mesenchymal stem cells MicroRNA-29a Intra-articular injection

Insight into effects of egg- and soybean-derived phosphatidylcholine on non-alcoholic steatosis in mice and HepG2 cells by lipidomics

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Food Science and Human Wellness 2024年

作者： Zhihui Yu Chunyou liu Yating Gao Haoran Guo Huiling Duan Lixin Zhang Yisheng Chen College of Food Science and Engineering Shanxi Agricultural University Institute of Food Nutrition and Safety Shanxi Agricultural University Department of Food Science and Technology Guangxi University of Science and Technology

Dietary phosphatidylcholine (PC) is an ideal source of bioactive lipids showing efficacy to alleviate non-alcoholic fatty liver disease (NAFLD). In this study， the lipidomic profiles of nonalcoholic steatosis in mice and HepG2 cells treated with PC isolated from eggs (EPC) and soybean (SPC) were evaluated. EPC and SPC could significantly ameliorate fatty liver disease by down-regulating triglyceride (TG) and diglyceride (DG) levels. Remarkably， EPC exhibited better performance in regulating the hepatic lipid profile leading to decreased PC and TG， ceramides， phosphatidylethanolamine and phosphatidylserine levels. A total of 117 and 20 lipid biomarkers in liver and HepG2 cells involved in glycerophospholipid metabolism were screened out， respectively. The regulatory mechanism of EPC may be attributed to a decrease in the expression of ACACA and SREBP-1c. EPC， via suppressing lipogenic gene expression， which was superior to that of SPC in alleviating nonalcoholic steatosis. Overall， EPC and SPC attenuated HFD-induced NAFLD by improving the hepatic lipid profile. The more significant effect observed with EPC may be attributed to its modulation of glycerophospholipid metabolism.

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建设金融强国的历史逻辑和实现路径

金融监管研究 2024年第6期 1-6页

作者：刘伟刘志清北京交通大学语言与传播学院国家金融监督管理总局统计监测司

中央金融工作会议首次提出“加快建设金融强国”的战略目标。2024年1月,习近平总书记在省部级主要领导干部推动金融高质量发展专题研讨班开班式上发表重要讲话,深刻阐释了金融强国的丰富内涵,并强调中国金融发展之路既遵循现代金融发展... 详细信息

中央金融工作会议首次提出“加快建设金融强国”的战略目标。2024年1月,习近平总书记在省部级主要领导干部推动金融高质量发展专题研讨班开班式上发表重要讲话,深刻阐释了金融强国的丰富内涵,并强调中国金融发展之路既遵循现代金融发展的客观规律,更具有适合我国国情的鲜明特色,与西方金融模式有本质区别。因此,我国建设金融强国的历史逻辑和实现路径与西方金融模式有着根本的不同,我们要坚定不移走中国特色金融发展之路。

关键词：金融模式金融强国中国金融发展实现路径战略目标现代金融发展特色金融主要领导干部

Narrowband blue emitter based on fused nitrogen/carbonyl combination with external quantum efficiency approaching 30%

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Science China Chemistry 2024年第1期67卷 351-359页

作者： Long Chen Jia-Heng Cai You-Jun Yu Yang-Kun Qu Sheng-Yi Yang Sheng-Nan Zou Rui-Hong liu Dong-Ying Zhou Liang-Sheng Liao Zuo-Quan Jiang Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhou 215123China Macao Institute of Materials Science and Engineering Macao University of Science and TechnologyMacao 999078China

Multi-resonance thermally activated delayed fluorescence(MR-TADF)emitters can enable narrowband emission with high color purity and electroluminescence efficiency.Nitrogen/carbonyl(N/C=O)system is receiving increasing attention while the nitrogen/boron(N/B)system has been widely studied.Donor decoration is an effective approach for N/B type MR-TADF system but always leads to broadening and red-shifting of the emission band in N/C=O MR-TADF system.We attribute these unfavorable phenomena to the formation of intramolecular charge transfer between the MR-core and peripheral donors.To address this issue,we have developed a new strategy by decorating DMQAO(a fused N/C=O MR-core)with a triazine acceptor and a neutral terphenyl group to construct MTDMQAO and MBDMQAO,respectively.The introduction of the triazine acceptor not only realizes efficient narrowband emission in MTDMQAO,but also accelerates the reverse intersystem crossing process through enhanced spin-orbital coupling.As a result,MTDMQAO exhibits a significantly higher external quantum efficiency of 29.4%compared to the referent emitters,validating the rationality of our derivation strategy.This study highlights the potential of the N/C=O system for MR-TADF emitters and provides important insights for understanding the difference between N/B and N/C=O systems.

关键词： carbonyl group narrowband acceptor decoration thermally activated delayed fluorescence OLEDs

阿拉伯海超级气旋风暴“查帕拉”(2015)快速加强过程中环境场特征

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热带气象学报 2024年第1期40卷 40-51页

作者：柳龙生刘莲高拴柱国家气象中心北京100081 中国科学院青藏高原研究所北京100101

利用美国联合台风警报中心(JTWC)发布的北印度洋热带气旋数据、NOAA 0.25°×0.25°逐日OISST资料以及ERA5提供的0.25°×0.25°逐小时的再分析资料分析了阿拉伯海超级气旋风暴“查帕拉”(2015)快速加强过程中的环境场特征,结果表明:较... 详细信息

利用美国联合台风警报中心(JTWC)发布的北印度洋热带气旋数据、NOAA 0.25°×0.25°逐日OISST资料以及ERA5提供的0.25°×0.25°逐小时的再分析资料分析了阿拉伯海超级气旋风暴“查帕拉”(2015)快速加强过程中的环境场特征,结果表明:较常年平均偏暖3.0~3.5℃的暖水区,为“查帕拉”的快速加强提供了水汽和能量条件;“查帕拉”北侧的副热带西风急流和南侧的高空出流通道的建立是其快速加强的重要高空强迫条件,高层辐散风的增强促进质量流出形成强上升运动,这也伴随着旋转风动能的快速增长;在“查帕拉”快速增强时段,高层150 hPa以上存在显著的正位涡异常,高层的正位涡异常能够调整引起低层气旋性环流加强,同时中层400 hPa有显著的正位涡平流输入,正涡度在垂直方向快速增长,300 hPa附近显著增暖,内核区的垂直对流运动达到最强。

关键词：查帕拉快速加强高空出流涡度位涡