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Construction of a mutant of Actinoplanes sp. N902-109 that produces a new rapamycin analog

Chinese Journal of Natural Medicines 2018年第3期16卷 210-218页

作者： HUANG He gao Ping zhao Qi HU Hai-feng Shanghai Institute of Pharmaceutical Industry Shanghai 201203 China Institute of Plant Physiology and Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China

In the present study, we introduced point mutations into Ac_rap A which encodes a polyketide synthase responsible for rapamycin biosynthesis in Actinoplanes sp. N902-109, in order to construct a mutant with an inactivated enoylreductase(ER) domain, which was able to synthesize a new rapamycin analog. Based on the homologous recombination induced by double-strand breaks in chromosome mediated by endonuclease I-SceI, the site-directed mutation in the first ER domain of Ac_rapA was introduced using non-replicating plasmid pL YERIA combined with an I-SceI expression plasmid. Three amino acid residues of the active center, Ala-Gly-Gly, were converted to Ala-Ser-Pro. The broth of the mutant strain SIPI-027 was analyzed by HPLC and a new peak with the similar UV spectrum to that of rapamycin was found. The sample of the new peak was prepared by solvent extraction, column chromatography, and crystallization methods. The structure of new compound, named as SIPI-rapxin, was elucidated by determining and analyzing its MS and NMR spectra and its biological activity was assessed using mixed lymphocyte reaction(MLR). An ER domain–deficient mutant of Actinoplanes sp. N902-109, named as SIPI-027, was constructed, which produced a novel rapamycin analog SIPI-rapxin and its structure was elucidated to be 35, 36-didehydro-27-O-demethylrapamycin. The biological activity of SIPI-rapxin was better than that of rapamycin. In conclusion, inactivation of the first ER domain of rap A, one of the modular polyketide synthase responsible for macro-lactone synthesis of rapamycin, gave rise to a mutant capable of producing a novel rapamycin analog, 35, 36-didehydro-27-O-demethylrapamycin, demonstrating that the enoylreductase domain was responsible for the reduction of the double bond between C-35 and C-36 during rapamycin synthesis.

关键词： Actinoplanes sp. N902-109 Rapamycin Structural analog Polyketide synthase Enoylreductase

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The application of co-integration theory in ensemble pulsar timescale algorithm

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Research in Astronomy and Astrophysics 2019年第7期19卷 115-122页

作者： feng gao Ming-Lei Tong Yu-Ping gao Ting-gao Yang Cheng-Shi zhao National Time Service Center Chinese Academy of SciencesXi'an 710600China Key Laboratory of Time and Frequency Primary Standards Chinese Academy of SciencesXi'an 710600China University of Chinese Academy of Sciences Beijing 100049China Department of Applied Physics Xi'an University of Science and TechnologyXi'an 710054China

Employing multiple pulsars and using an appropriate algorithm to establish ensemble pulsar timescale can reduce the influences of various noises on the long-term stability of pulsar timescale,compared to a single ***,due to the low timing precision and significant red noises of some pulsars,their participation in the construction of ensemble pulsar timescale is often *** by the principle of solving non-stationary sequence modeling using co-integration theory,we put forward an algorithm based on co-integration theory to establish an ensemble pulsar *** is found that this algorithm can effectively suppress some noise sources if a co-integration relationship between different pulsar data *** from the classical weighted average algorithm,the co-integration method provides the chance for a pulsar with significant red noises to be included in the establishment of an ensemble pulsar *** on data from the North American Nanohertz Observatory for Gravitational Waves(NANOGrav),we found that the co-integration algorithm can successfully reduce several timing noises and improve the long-term stability of the ensemble pulsar timescale.

关键词： pulsars general-time-methods analytical

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Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease

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Neural Regeneration Research 2025年第3期20卷 613-631页

作者： Yanxin Shen Guimei Zhang Chunxiao Wei Panpan zhao Yongchun Wang Mingxi Li Li Sun Department of Neurology and Neuroscience Center The First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina Cognitive Impairment Center Department of NeurologyThe First Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinica

关键词： apoptosis ferroptosis inflammation lipid peroxidation natural plant products neurodegenerative disorder neuroprotection oxidative stress small-molecule drugs

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Use of ryegrass strips to enhance biological control of aphids by ladybirds in wheat fields

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Insect Science 2012年第4期19卷 529-534页

作者： zhao-Ke Dong feng-Juan gao Run-Zhi Zhang Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of Sciences Graduate University ofChinese Academy of Sciences State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijingChina

Non-crop habitats may play a vital role in conservation biological control. This study tested the effect of ryegrass （Lolium multiflorum L.） strips on aphid and la- dybird populations in adjacent winter wheat fields. The field experiment was conducted in three ryegrass-margin wheat plots and three control plots in 2010 in North China. In spring, the same aphid species, Sitobion miscanthi （Takahashi）, was found in both the ryegrass strips and wheat plots. The population density of ladybirds in the ryegrass strips （3.5 4- 0.9/m2） was significantly higher than in the wheat plots （1.5 4- 0.5/m2）. We cut the ryegrass, forcing the ladybirds to migrate to the wheat fields. Three and eight days after cutting the ryegrass, the aphid numbers in the ryegrass-margin wheat plots decreased significantly： they were 19.9% and 53.6%, respectively, lower than in control plots. In the early period of ladybird population development, the percentage of larvae was greater in the ryegrass-margin wheat plots than in controls, and the peak number of pupae in the ryegrass-margin wheat plots occurred 5 days earlier than in the control plots. The results suggest that ryegrass strips may promote the development of ladybird populations. Cutting ryegrass can manipulate ladybirds to enhance biological aphid control in wheat fields. The efficiency of this management approach is discussed.

关键词： coccinellids habitat management natural enemies non-crop habitat

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Convolution Theorem Associated with the QWFRFT

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Chinese Journal of Electronics 2023年第3期32卷 485-492页

作者： MEI Yinyin feng Qiang gao Xiuxiu zhao Yanbo School of Mathematics and Computer Science Yan’an University

The quaternion windowed fractional Fourier transform(QWFRFT) is a generalized form of the quaternion fractional Fourier transform(QFRFT), it plays a crucial role in signal processing for the analysis of multidimensional signals. In this paper, we first give the definition of the two-sided QWFRFT and some fundamental properties. Then, the quaternion convolution is proposed, and the relation between the quaternion convolution and the classical convolution is also given. Based on the quaternion convolution of the QWFRFT, relevant convolution theorems for the QWFRFT are ***, the fast algorithm for QWFRFT is ***, the complexity of QWFRFT and the quaternion windowed fractional convolution are given.

关键词： Fourier transforms Convolution Algebra Quaternions Signal processing algorithms Color Complexity theory

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多层陶瓷电容器应用与可靠性研究

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环境技术 2016年第2期34卷 21-25页

作者：彭浩席善斌裴选高兆丰黄杰中国电子科技集团公司第十三研究所石家庄050051 国家半导体器件质量监督检验中心石家庄050051

多层陶瓷电容器(MLCC)在使用过程中电参数会发生不同程度的退化甚至超差失效,降低了其可靠性。引起失效的原因可分为损耗性失效、过应力失效、内部缺陷失效以及外部缺陷失效四类。基于日常失效分析工作中遇到的多层陶瓷电容器失效问题,... 详细信息

多层陶瓷电容器(MLCC)在使用过程中电参数会发生不同程度的退化甚至超差失效,降低了其可靠性。引起失效的原因可分为损耗性失效、过应力失效、内部缺陷失效以及外部缺陷失效四类。基于日常失效分析工作中遇到的多层陶瓷电容器失效问题,结合国内外文献调研资料,首先对多层陶瓷电容器制造工艺进行了分析,然后对烧结裂纹、分层及空洞三种内在缺陷以及使用过程中外部应力引起的装配裂纹、热应力裂纹、弯曲裂纹、银迁移等失效模式及其相应的微观失效机理展开了深入讨论,最后对上述失效提出了相应建议和预防措施。

关键词：多层陶瓷电容器制造工艺失效分析微观机理

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Distributed fiber optic sensing system for vibration monitoring of 3D printed bridges

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Optoelectronics Letters 2025年第1期21卷 28-34页

作者： zhao Shuai ZHOU Ran LUO Mingming LIU Jianfei LIU Xiongfei ZHOU Tao School of Electronic Information Engineering Hebei University of Technology Tianjin Key Laboratory of Electronic Materials and Devices School of Civil Engineering and Transportation Hebei University of Technology Tianjin Jinhang Institute of Technical Physics

The fiber optic sensing technology provides data support in structural health monitoring of the macro facilities, including design, construction, and maintenance of bridges, tunnels, ports and other infrastructures. In this paper, a distributed vibration sensing system is proved to be responsive to a single touch over a 1.8-m-long equivalent fiber segment, covering a vibration frequency from 5 Hz to 25 kHz. The sensing fiber was arranged as an S type layout on the bridge to recognize the standing state, windblown disturbance, and walking vibration. Moreover, the knocking and climbing events are recognized fiber laying spinning lines and hanging on the fences, respectively. The demonstration shows an accurate positioning and sensitive vibration monitoring applied on the automated three-dimensional(3D) printed bridge, which is applicable to all kinds of 3D printed facilities as intelligent sensory neuro-networks.

关键词： Spinning (fibers)

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Fragmentation Energy-Saving Theory of Full Face Rock Tunnel Boring Machine Disc Cutters

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Chinese Journal of Mechanical Engineering 2017年第4期30卷 913-919页

作者： zhao-Huang Zhang Guo-Fang Gong Qing-feng gao Fei Sun School of Energy Power and Mechanical EngineeringNorth China Electric Power UniversityBeijing 102206China State Key Laboratory of Fluid Power Transmission and Control Zhejiang UniversityHangzhou 310027China School of Foreign Languages North China Electric Power UniversityBeijing 102206China

Attempts to minimize energy consumption of a tunnel boring machine disc cutter during the process of fragmentation have largely focused on optimizing disc- cutter spacing, as determined by the minimum specific energy required for fragmentation; however, indentation tests showed that rock deforms plastically beneath the cutters. Equations for thrust were developed for both the traditional, popularly employed disc cutter and anew design based on three-dimensional theory. The respective energy consumption for penetration, rolling, and side-slip fragmentations were obtained. A change in disc-cutter fragmentation angles resulted in a change in the nature of the interaction between the cutter and rock, which lowered the specific energy of fragmentation. During actual field excavations to the same penetration length, the combined energy consumption for fragmentation using the newly designed cutters was 15% lower than that when using the traditional design. This paper presents a theory for energy saving in tunnel boring machines. Investigation results showed that the disc cutters designed using this theory were more durable than traditional designs, and effectively lowered the energy consumption.

关键词： Newly design Disc cutter Fragmentation Specific energy Energy consumption

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Influence of Self-excited Vibrating Cavity Structure on Droplet Diameter Characteristics of Twin-fluid Nozzle

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Chinese Journal of Mechanical Engineering 2018年第4期31卷 192-201页

作者： Bo Chen Dian-Rong gao Shao-feng Wu Jian-Hua zhao School of Mechanical Engineering Yanshan University School of Mechanical Engineering Hangzhou Dianzi University State Key Laboratory of Fluid Power and Mechatronic Systems Zhejiang University

It is a great challenge to find effective atomizing technology for reducing industrial pollution; the twin-fluid atomizing nozzle has drawn great attention in this field recently. Current studies on twin-fluid nozzles mainly focus on droplet breakup and single droplet characteristics. Research relating to the influences of structural parameters on the droplet diameter characteristics in the flow field is scarcely available. In this paper, the influence of a self-excited vibrating cavity structure on droplet diameter characteristics was investigated. Twin-fluid atomizing tests were performed by a self-built open atomizing test bench, which was based on a phase Doppler particle analyzer(PDPA). The atomizing flow field of the twin-fluid nozzle with a self-excited vibrating cavity and its absence were tested and analyzed. Then the atomizing flow field of the twin-fluid nozzle with different self-excited vibrating cavity structures was *** experimental results show that the structural parameters of the self-excited vibrating cavity had a great effect on the breakup of large droplets. The Sauter mean diameter(SMD) increased with the increase of orifice diameter or orifice depth. Moreover, a smaller orifice diameter or orifice depth was beneficial to enhancing the turbulence around the outlet of nozzle and decreasing the SMD. The atomizing performance was better when the orifice diameter was2.0 mm or the orifice depth was 1.5 mm. Furthermore, the SMD increased first and then decreased with the increase of the distance between the nozzle outlet and self-excited vibrating cavity, and the SMD of more than half the atomizing flow field was under 35 μm when the distance was 5.0 mm. In addition, with the increase of axial and radial distance from the nozzle outlet, the SMD and arithmetic mean diameter(AMD) tend to increase. The research results provide some design parameters for the twin-fluid nozzle, and the experimental results could serve as a beneficial suppleme

关键词： Atomizing nozzle Twin-fluid Sauter mean diameter Arithmetic mean diameter Self-excited vibrating cavity Phase Doppler particle analyzer

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Hypoxia-mediated programmed cell death is involved in the formation of wooden breast in broilers

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Journal of Animal Science and Biotechnology 2024年第5期15卷 1918-1931页

作者： Xinrui Zhang Tong Xing Lin Zhang Liang zhao feng gao College of Animal Science and Technology Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu ProvinceJiangsu Collaborative Innovation Center of Meat Production and ProcessingQuality and Safety ControlNanjing Agricultural UniversityNo.1 WeigangNanjingJiangsu 210095P.R.China

Background Wooden breast(WB)myopathy is a common myopathy found in commercial broiler chickens *** examination has revealed that WB myopathy is accompanied by damage to the pectoralis major(PM)***,the underlying mechanisms responsible for the formation of WB in broilers have not been fully *** study aimed to investigate the potential role of hypoxia-mediated programmed cell death(PCD)in the formation of WB *** Histological examination and biochemical analysis were performed on the PM muscle of the control(CON)and WB groups.A significantly increased thickness of the breast muscle in the top,middle,and bottom portions(P<0.01)was found along with pathological structure damage of myofibers in the WB *** number of capillaries per fiber in PM muscle,and the levels of p O_(2) and s O_(2) in the blood,were significantly decreased(P<0.01),while the levels of p CO_(2) and TCO_(2) in the blood were significantly increased(P<0.05),suggesting hypoxic conditions in the PM muscle of the WB *** further evaluated the PCD-related pathways including autophagy,apoptosis,and necroptosis to understand the consequence response to enhanced hypoxic conditions in the PM muscle of birds with *** ratio of LC3 II to LC3 I,and the autophagy-related factors HIF-1α,BNIP3,Beclin1,AMPKα,and ULK1 at the m RNA and protein levels,were all significantly upregulated(P<0.05),showing that autophagy occurred in the PM muscle of the WB *** apoptotic index,as well as the expressions of Bax,Cytc,caspase 9,and caspase 3,were significantly increased(P<0.05),whereas Bcl-2 was significantly decreased(P<0.05)in the WB-affected PM muscle,indicating the occurrence of apoptosis mediated by the mitochondrial ***,the expressions of necroptosis-related factors RIP1,RIP3,and MLKL,as well as NF-κB and the pro-inflammatory cytokines TNF-α,IL-1β,and IL-6,were all significantly enhanced(P<0.05)in the WB-affected PM *** T

关键词： Apoptosis Autophagy Broiler chicken Hypoxia Necroptosis Wooden breast

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