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Discovery of thiosemicarbazone derivatives as effective New Delhi metallo-β-lactamase-1(NDM-1) inhibitors against NDM-1 producing clinical isolates

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Acta Pharmaceutica Sinica B 2021年第1期11卷 203-221页

作者： Bing Zhao Xinhui Zhang Tingting Yu Ying Liu Xiaoling Zhang Yongfang Yao xuejian feng Hongmin Liu Dequan Yu Liying Ma Shangshang Qin State Key Laboratory of Esophageal Cancer Prevention and Treament Key Laboratory of Technology of Drug Preparation(Zhengzhou University)Ministry of Education of ChinaKey Laboratory of Henan Province for Drug Quality and EvaluationInstitute of Pharmaceutical Research and School of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

New Delhi metallo-b-lactamase-1(NDM-1)is capable of hydrolyzing nearly allβ-lactam antibiotics,posing an emerging threat to public health.There are currently less effective treatment options for treating NDM-1 positive"superbug",and no promising NDM-1 inhibitors were used in clinical practice.In this study,structure eactivity relationship based on thiosemicarbazone derivatives wassystematically characterized and their potential activities combined with meropenem(MEM)were evaluated.Compounds 19 bg and 19 bh exhibited excellent activity against 10 NDM-positive isolate clinical isolates in reversing MEM resistance.Further studies demonstrated compounds 19 bg and 19 bh were uncompetitive NDM-1 inhibitors with Ki Z 0.63 and 0.44 mmol/L,respectively.Molecular docking speculated that compounds 19 bg and 19 bh were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem.Toxicity evaluation experiment showed that no hemolysis activities even at concentrations of 1000 mg/m L against red blood cells.In vivo experimental results showed combination of MEM and compound 19 bh was markedly effective in treating infections caused by NDM-1 positive strain and prolonging the survival time of sepsis mice.Our finding showed that compound 19 bh might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.

关键词： Thiosemicarbazone derivatives New Delhi metallo-β-lactamase-1 Inhibitor Antibiotic resistance

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Norovirus P particle-based tau vaccine-generated phosphorylated tau antibodies markedly ameliorate tau pathology and improve behavioral deficits in mouse model of Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2021年第3期6卷 593-595页

作者： Yao Sun Yongqing Guo xuejian feng Lu Fu Yayuan Zheng Yue Dong Yong Zhang Xianghui Yu' Wei Kong Hui Wu National Engineering Laboratory for AIDS Vaccine School of Life SciencesJilin UniversityChangchun 130012China Laboratory of Pathogenic Microbiology and Immunology College of Life ScienceJilin Agricultural UniversityChangchun 130012China Key Laboratory for Molecular Enzymology and Engineering the Ministry of EducationSchool of Life SciencesJilin UniversityChangchun 130012China

Dear Editor,Currently,there are no FDA-approved disease-modifying therapies that can prevent,halt,or reverse Alzheimer's disease(AD).As the unsatisfactory of amyloid-p-targeted treatment in recent years,development of Tau-targeted active immunotherapy takes much concern.1 Tau protein,a major microtubule-associated protein in the nervous system,was found to be abnormally hyperphosphorylated at six epitopes:Ser396/404,Ser202,Thr205,Ser238,and Ser262 in AD patients.2 Hence,immunotherapy targeting more highly-expressed phosphorylated Tau(pTau)species may induce a sufficient pool of pTau antibodies to eliminate pathological tau and elicit cognitive improvement.

关键词： tau markedly Alzheimer

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滩羊红外热成像温度与直肠温度的关系研究

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宁夏农林科技 2024年第2期65卷 52-56页

作者：张建华张学俭李锋宁夏农林科学院农业经济与信息技术研究所宁夏银川750002

为提高对羊场滩羊健康、发情、应激和疫病的监测预警能力,实现滩羊体温的快速、非接触、无应激获取,采集50只6月龄母滩羊直肠温度,以及特征区域眼睛、耳朵和鼻子红外热成像(Infrared thermography,IRT)温度数据,研究利用局部IRT温度替... 详细信息

为提高对羊场滩羊健康、发情、应激和疫病的监测预警能力,实现滩羊体温的快速、非接触、无应激获取,采集50只6月龄母滩羊直肠温度,以及特征区域眼睛、耳朵和鼻子红外热成像(Infrared thermography,IRT)温度数据,研究利用局部IRT温度替代体温(直肠温度)的测量方法。通过统计分析发现,直肠温度和眼睛IRT温度离散度较小、稳定性较强,眼睛IRT温度受直肠温度影响最大,与直肠温度呈显著正相关关系,也最接近直肠温度且方便测量。因此,将眼睛作为滩羊红外热成像测温部位,采用线性模型和多项式数学模型构建滩羊IRT温度与直肠温度关系模型,并进行测试组数据拟合比较,结果表明,线性模型平均绝对误差为0.215℃,平均相对误差为0.548%,拟合度最优,精准度最高,可用于检测滩羊体温。

关键词：滩羊红外热成像直肠温度体温预测模型

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基于合成数据的刚体姿态实时估计网络

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计算机测量与控制 2024年第5期32卷 282-289页

作者：刘千山林雪剑朱枫李佩东国能宝日希勒能源有限公司内蒙古呼伦贝尔021500

现有刚体姿态估计存在数据稀缺、复杂场景下的低鲁棒性及低实时性等问题,为此提出一种基于合成数据的刚体目标位姿追踪网络结构;采用时空间特征融合技术,捕捉时间与空间特征信息,生成具有时空敏感的特征图;利用残差连接学习更为丰富和... 详细信息

现有刚体姿态估计存在数据稀缺、复杂场景下的低鲁棒性及低实时性等问题,为此提出一种基于合成数据的刚体目标位姿追踪网络结构;采用时空间特征融合技术,捕捉时间与空间特征信息,生成具有时空敏感的特征图;利用残差连接学习更为丰富和抽象的优质特征,改善追踪目标的准确性;对稀缺数据进行数据增强,生成符合现实物理特性的复杂合成数据,以此训练深度学习模型,提高模型的泛化性;在YCB-Video数据集中选取7个物体进行实时姿态追踪实验,结果表明,提出的方法相较于同类相关方法,在复杂场景下对刚体姿态估计的更为准确,在实时估计效率上表现最优。

关键词：姿态追踪数据稀缺时空特征融合残差连接数据增强

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不同变质程度煤的吸附瓦斯动力学特性实验研究

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煤矿安全 2024年第1期55卷 34-41页

作者：王梦露沈永星周动王辰王金鑫冯雪健太原理工大学安全与应急管理工程学院山西太原030002 太原理工大学原位改性采矿教育部重点实验室山西太原030024 华北科技学院安全工程学院河北三河065201

为了进一步揭示不同变质程度的煤在不同吸附压力下的动力学特征,利用自主研发的TQY-2型精密吸附仪和红外热成像装置对直径为8.5 mm的褐煤、焦煤和无烟煤煤样进行不同压力(0.2、0.4、0.6、0.8、1.0 MPa)下的宏观吸附试验和吸附压力为(0.3... 详细信息

为了进一步揭示不同变质程度的煤在不同吸附压力下的动力学特征,利用自主研发的TQY-2型精密吸附仪和红外热成像装置对直径为8.5 mm的褐煤、焦煤和无烟煤煤样进行不同压力(0.2、0.4、0.6、0.8、1.0 MPa)下的宏观吸附试验和吸附压力为(0.3、0.6、0.9、1.2、1.5 MPa)的煤体细观结构吸附试验,利用准一级、准二级、颗粒内扩散、Elovich以及双常数等吸附动力学模型分析吸附瓦斯规律及机理。研究表明:对比5种吸附动力学模型,准二级吸附动力学模型适合表征褐煤和焦煤的吸附瓦斯过程,而无烟煤的最优模型为颗粒内扩散模型;随着吸附压力升高,褐煤和焦煤的准二级吸附速率常数k2逐渐增加,无烟煤的颗粒内扩散速率常数kp也逐渐增加,均呈正相关;吸附压力对煤样适合的动力学模型影响较小;在宏观吸附和基于红外热成像的煤体细观结构吸附实验下,煤样适合的动力学模型一致。

关键词：不同变质程度不同压力瓦斯吸附动力学吸附速率

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Quantitative Rectangular Notch Detection of Laser-induced Lamb Waves in Aluminium Plates with Wavenumber Analysis

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Transactions of Nanjing University of Aeronautics and Astronautics 2018年第2期35卷 244-255页

作者： Liu Zenghua feng xuejian He Cunfu Wu Bin College of Mechanical Engineering and Applied Electronics Technology Beijing University of Technology Beijing Engineering Research Center of Precision Measurement Technology and Instruments Beijing University of Technology

It is difficult to quantitatively detect defects by using the time domain or frequency domain features of Lamb wave signals due to their dispersion and multimodal characteristics.Therefore,it is important to discover an intrinsical parameter of Lamb waves that could be used as a damage sensitive feature.In this paper,quantitative defect detection in aluminium plates is carried out by means of wavenumber analysis approach.The wavenumber of excited Lamb wave mode is a fixed value,given a frequency,a thickness and material properties of the target plate.When Lamb waves propagate to the structural discontinuity,new wavenumber components are created by abrupt wavefield change.The new wavenumber components can be identified in the frequency-wavenumber domain.To estimate spatially dependent wavenumber values,a short-space two-dimensional Fourier transform(FT)method is presented for processing wavefield data of Lamb waves.The results can be used to determine the location,size and depth of rectangular notch.The analysis techniques are demonstrated using simulation examples of an aluminium plate with a rectangular notch.Then,the wavenumber analysis method is applied to simulation data that are obtained through a range of notch depths and widths.The results are analyzed and rules of the technique with regards to estimating notch depth are determined.Based on simulation results,guidelines for using the technique are developed.Finally,experimental wavefield data are obtained in aluminium plates with rectangular notches by a full noncontact transceiving method,i.e.,laser-laser method.Band-pass filtering combined with continuous wavelet transform is used to extract a certain frequency component from the full laser-induced wavefield with wide band.Shortspace two-dimensional FT method is used for further processing full wavefield data at a certain frequency to estimate spatially dependent wavenumber values.The consistency of simulation and experimental results shows the effectiveness of proposed wavenumber method for quantitative

关键词： wavenumber analysis short space two-dimensional Fourier transform(FT) notch aluminium plate

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Correction to:Norovirus P particle-based tau vaccinegenerated phosphorylated tau antibodies markedly ameliorate tau pathology and improve behavioral deficits in mouse model of Alzheimer’s disease

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Signal Transduction and Targeted Therapy 2021年第7期6卷 2252-2253页

作者： Yao Sun Yongqing Guo xuejian feng Lu Fu Yayuan Zheng Yue Dong Yong Zhang Xianghui Yu Wei Kong Hui Wu National Engineering Laboratory for AIDS Vaccine School of Life Sciences Jilin University Changchun 130012 China Key Laboratory for Molecular Enzymology and Engineering the Ministry of Education School of Life Sciences Jilin University Changchun 130012 China Laboratory of Pathogenic Microbiology and Immunology College of Life Science Jilin Agricultural University Changchun 130012 China

In the process of collating the published data,the authors noticed one inadvertent mistake occurred during the production process in Fig.1u that needs to be corrected.1 The authors mistakenly placed the wrong western blot figure for the level of pTauS404 in the urea fraction of mice from the onset cohort in Fig.lu.The correct data are provided as follows.The key findings of the article are not affected by these corrections.The original article has been corrected.

关键词： markedly tau corrected

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Effects of various donor:acceptor blend ratios on photophysical properties in non-fullerene organic bulk heterojunctions

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Chinese Chemical Letters 2019年第5期30卷 995-999页

作者： Zhenchuan Wen xuejian Ma Xiaoyu Yang Pengqing Bi Mengsi Niu Kangning Zhang Lin feng Xiaotao Hao School of Physics State Key Laboratory of Crystal MaterialsShandong UniversityJi'nan 250100China ARC Centre of Excellence in Exciton Science School of ChemistryThe University of MelbourneParkvilleVictoria3010Australia

The composition ratio of donor and acceptor materials in organic bulk heterojunction (BHJ) is one of the key parameters to govern the performance in organic solar cells (OSCs). Therefore, high-performance non-fullerene organic bulk heterojunction consisting of poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b:4,5-b' ]dithiophene))-co-(1,3-di(5-thiophene-2-yl)–5,7-bis(2-ethylhexyl) benzo[1,2-c:4,5-c']dithiophene-4,8-dione)] (PBDB-T) and 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))–5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2' ,3'-d' ]-s-indaceno[1,2-b:5,6-b' ]-dithio-phene (ITIC) are used to investigate the correlation among various donor: acceptor (D:A) ratios, photophysical properties and photovoltaic performance. Interestingly, the function of short-circuit current (Jsc) and D:A ratios demonstrates an axisymmetric trend. When the blending ratio of D:A deviates from the optimal ratio, the symmetrically decreased Jsc is derived from a reduction in the D:A interface or amorphous region. Research on the steady-state photoluminescence (PL), the time-resolved fluorescence spectroscopy measurements, atomic force microscopic (AFM) and grazing-incidence small angle X-rays scattering (GIWAXS) indicates no significant variation in energy loss in the process of changing D:A ratios in BHJs. With high donor or acceptor content, the domain size improves significantly, but the distance of π-π stacking corresponding to molecular packing has not changed significantly, and the bi-continuous percolation pathways were not obviously influenced.

关键词： Photophysical properties Non-fullerene Bulk heterojunctions Various blend ratios Organic solar cells

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Optical fiber SPR biosensor complying with a 3D composite hyperbolic metamaterial and a graphene film

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Photonics Research 2021年第3期9卷 379-388页

作者： Can Li Jinjuan Gao Muhammad Shafi Runcheng Liu Zhipeng Zha Dejun feng Mei Liu xuejian Du Weiwei Yue Shouzhen Jiang Collaborative Innovation Center of Light Manipulations and Applications in Universities of Shandong School of Physics and Electronics Shandong Normal UniversityJinan 250014China Shandong Key Laboratory of Medical Physics and Image Processing&Shandong Provincial Engineering and Technical Center of Light Manipulations Jinan 250014China School of Information Science and Engineering Shandong UniversityQingdao 266237China Shandong Key Laboratory of Biophysics Institute of BiophysicsDezhou UniversityDezhou 253023China

In the present study, an optical fiber surface plasmon resonance(SPR) biosensor was developed for measuring time-and concentration-dependent DNA hybridization kinetics. Its design complies with a 3D Au∕Al2O3 multilayer composite hyperbolic metamaterial(HMM), a graphene film, and a D-shaped plastic optical fiber.According to the numerical simulation and the experimental demonstration, the SPR peak of the designed biosensor can be effectively altered in the range of visible to near-infrared by varying the HMM structure. The sensitivity of the appliance was shown to achieve a value of up to 4461 nm/RIU, allowing its applicability for bulk refractive index sensing. Furthermore, a biosensor designed in this work displayed high-resolution capability(ranging from 10 pM to 100 nM), good linearity, and high repeatability along with a detection limit down to 10 pM, thus suggesting a vast potential for medical diagnostics and clinical applications.

关键词： fiber film composite

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数字技术与思想政治教育高质量发展的耦合逻辑及风险防范

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北京工业大学学报（社会科学版） 2023年第3期23卷 37-45页

作者：王学俭冯瑞芝兰州大学马克思主义学院甘肃兰州730000

数字技术是引领新时代思想政治教育高质量发展的新动能,数字技术与思想政治教育在结构、功能、价值上的耦合,为数字赋能新时代思想政治教育高质量发展提供了适切性、可行性证明。数字技术在促进思想政治教育升级迭代和实效提升的同时也... 详细信息

数字技术是引领新时代思想政治教育高质量发展的新动能,数字技术与思想政治教育在结构、功能、价值上的耦合,为数字赋能新时代思想政治教育高质量发展提供了适切性、可行性证明。数字技术在促进思想政治教育升级迭代和实效提升的同时也面临着一定的风险:一是数字嵌入思想政治教育的张力失度带来的数字悬浮、数字依赖、数字至上等错误倾向;二是思想政治教育主体呈现出人的自我、人与人、人与教育、人与社会之间的关系的失调和异化倾向;三是思想政治教育数据的过度采集和滥用带来的数据过载、隐私侵犯、数据安全等风险挑战;四是算法不当产生的算法偏见、信息茧房、算法黑箱等问题。针对数字赋能思想政治教育面临的风险挑战,提出了具体的解决措施,即深化理念认识,明确数字技术赋能的战略定位;加强数字素养教育,发挥思想政治教育的育人价值;加强数字技术规范,促进技术势能的充分释放。

关键词：数字技术思想政治教育耦合逻辑教育高质量发展教育数字转型

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