41 results on '"Wang, Danlei"'
Search Results
2. A systematic review and meta-analysis of inflammatory biomarkers in Parkinson’s disease
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Qu, Yi, Li, Jiangting, Qin, Qixiong, Wang, Danlei, Zhao, Jingwei, An, Ke, Mao, Zhijuan, Min, Zhe, Xiong, Yongjie, Li, Jingyi, and Xue, Zheng
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- 2023
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3. CXCR4-mediated neutrophil dynamics in periodontitis
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Xu, Xuanwen, Li, Tiange, Tang, Jingqi, Wang, Danlei, Zhou, Yi, Gou, Huiqing, Li, Lu, and Xu, Yan
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- 2024
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4. Multi-reservoir ESN-based prediction strategy for dynamic multi-objective optimization
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Yang, Cuili, Wang, Danlei, Tang, Jian, Qiao, Junfei, and Yu, Wen
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- 2024
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5. Freezing of gait is a risk factor for cognitive decline in Parkinson’s disease
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Qu, Yi, Li, Jiangting, Chen, Yupeng, Li, Jingyi, Qin, Qixiong, Wang, Danlei, Zhao, Jingwei, Yang, Qingmei, Mao, Zhijuan, Xiong, Yongjie, Min, Zhe, and Xue, Zheng
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- 2023
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6. MicroRNA-218-5p-Ddx41 axis restrains microglia-mediated neuroinflammation through downregulating type I interferon response in a mouse model of Parkinson’s disease
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Wang, Danlei, Gao, Hongling, Qin, Qixiong, Li, Jingyi, Zhao, Jingwei, Qu, Yi, Li, Jiangting, Xiong, Yongjie, Min, Zhe, Mao, Zhijuan, and Xue, Zheng
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- 2024
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7. Biglycan regulated colorectal cancer progress by modulating enteric neuron-derived IL-10 and abundance of Bacteroides thetaiotaomicron
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Xu, Yuyu, Wang, Fei, Mi, Kai, Wang, Xinyuan, Wang, Danlei, Zhao, Qing, Wang, Jingjing, Liu, Zhi, Zhang, Qingqing, Liu, Yang, Zhang, Xuemei, and Liu, Xingyin
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- 2023
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8. α-Synuclein induces Th17 differentiation and impairs the function and stability of Tregs by promoting RORC transcription in Parkinson's disease
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Li, Jingyi, Zhao, Jingwei, Chen, Longmin, Gao, Hongling, Zhang, Jing, Wang, Danlei, Zou, Yuan, Qin, Qixiong, Qu, Yi, Li, Jiangting, Xiong, Yongjie, Min, Zhe, Yan, Manli, Mao, Zhijuan, and Xue, Zheng
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- 2023
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9. Electrode-free piezoelectric nanogenerator based on carbon black/polyvinylidene fluoride–hexafluoropropylene composite achieved via interface polarization effect
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Li, Yanan, Tong, Wangshu, Yang, Jie, Wang, Zhihao, Wang, Danlei, An, Qi, and Zhang, Yihe
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- 2023
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10. The effect of alkyl substitution on the oxidative metabolism and mutagenicity of phenanthrene
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Wang, Danlei, Schramm, Viktoria, Pool, Jeroen, Pardali, Eleni, Brandenburg, Annemarijn, Rietjens, Ivonne M. C. M., and Boogaard, Peter J.
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- 2022
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11. The influence of alkyl substitution on the in vitro metabolism and mutagenicity of benzo[a]pyrene
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Wang, Danlei, Groot, Angelique, Seidel, Albrecht, Wang, Lulu, Kiachaki, Effimia, Boogaard, Peter J., and Rietjens, Ivonne M.C.M.
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- 2022
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12. Robust echo state network with sparse online learning
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Yang, Cuili, Nie, Kaizhe, Qiao, Junfei, and Wang, Danlei
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- 2022
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13. Evaluation of custom posts and cores fabricated by two digital technologies in core and post space dimensions.
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Wu, Yumin, Qi, Haowen, Wang, Danlei, Liao, Mengyuan, Zhang, Yuhang, Zhang, Juan, and Xie, Haifeng
- Abstract
Purpose: To evaluate the adaptability between posts and post spaces and the rationality of cores fabricated by two digital custom post‐and‐core processes. Materials and Methods: Titanium post‐and‐cores were fabricated by digital scanning impression technology or digital scanning wax‐pattern technology on tooth defect molds of incisors, premolars, and molars, with traditional lost‐wax casts of these teeth as the controls. Micro‐CT and a laboratory scanner were used to determine intervals between post wall and root canal wall of the root apex, middle, and cervix of each sample in cross‐, sagittal, and coronal sections; intervals between the end of post and tooth; diameters of cervical, middle, and incisal part at cross‐, sagittal, and coronal sections of each sample, as well as shoulder widths. Results: The three fabrication processes showed significant differences in intervals between post‐and‐core prostheses and root canal walls, diameters of all parts of cores, and shoulder widths. Scanning impressions showed significant advantages in the main part of post‐and‐cores in incisors and premolars, while the scanning wax‐pattern process showed obvious inferiorities in premolars and molars. As to core spatial size, values of measured sites in the scanning impression process were closer to the standard than those of the traditional process, while differences between the measured value of the scanning wax‐pattern process were much more obvious than in the traditional process. Conclusions: The use of digital custom post‐and‐core scanning impressions improved the rationality and precision of post‐and‐core dimensions compared with two other processes. [ABSTRACT FROM AUTHOR]
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- 2024
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14. The Impact of Skill Level on the Integration of Information and Post-Error Adjustment during Action Anticipation in Basketball.
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Chen, Zhefu, Wang, Danlei, Fang, Wenxuan, and Luan, Mengkai
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EXPECTATION (Psychology) , *BASKETBALL , *VIDEO excerpts , *BASKETBALL players , *INFORMATION resources - Abstract
The present study examined the impact of skill level on the integration of contextual prior information and kinematic information alongside post-error adjustment during action anticipation in basketball. Twenty-three collegiate basketball players and twenty-three control participants engaged in anticipating as quickly and accurately as possible the outcomes of free throws, utilizing video clips depicting basketball players' actions, both with and without contextual prior information. Anticipatory performance and the difference in anticipatory performance following errors and correct responses were analyzed based on skill level and the congruency of contextual prior information (none, congruent, and incongruent). The findings revealed that the congruency of contextual prior information significantly affects action anticipation, with skill level moderating this effect. Moreover, skill level influenced the congruency effect on accuracy discrepancies between post-error and post-correct trials during action anticipation, with controls showing greater sensitivity to previous trial performance compared to experts. These results provide further evidence for the notion that individuals employ Bayesian reliability-based strategies to integrate different information sources and underscore the role of skill level in adjusting anticipatory judgments following errors during action anticipation. These insights contribute to a deeper understanding of the cognitive and behavioral mechanisms that differentiate skill levels in action anticipation, potentially guiding the development of targeted training interventions. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Self‐healing polyurethane based on a substance supplement and dynamic chemistry: Repair mechanisms and applications.
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Cao, Qi, Zhang, Lei, Zhang, Fenglei, Wang, Danlei, Wu, Dongfang, and Huang, Kai
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POLYURETHANES ,CHEMICAL bonds ,COVALENT bonds ,MECHANICAL efficiency ,HOLLOW fibers ,REPAIRING - Abstract
This review systematically summarizes the repair mechanisms and applications of self‐healing polyurethane (SHPU) materials aiming at energy conservation and safety under different repair methods. As of now, the repair methods that have emerged can be divided into two categories: substance landfill and bond repair. In terms of the repair mechanisms for both, the former involves the release of healing agents from micro‐carriers (microcapsules, hollow fibers, and microvascular) to fill the damaged area upon external impact. In contrast, bond repair combines physical and chemical changes triggered by light, heat, and other factors. To achieve efficient self‐healing in this mode, both the reorganization of broken chemical bonds and the high mobility of chain segments are crucial. Reversible covalent bonds and supramolecular interactions, as two branches of aforementioned reversible chemical bonds, share the responsibility for maintaining efficient self‐healing despite infinite cycling. Additionally, multiple synergistic crosslinked networks, special nanomaterials, and microphase separation are often used to solve the problem of incompatible healing efficiency and mechanical strength in bond repair. When the perspective is focused on the application, this gradually improved SHPU with strong potential and comprehensive performance has provided raw materials for many fields related to human development, such as road, architecture, healthcare, and electronic. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Piezoionic High Performance Hydrogel Generator and Active Protein Absorber via Microscopic Porosity and Phase Blending.
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Lu, Xi, Chen, Yao, Zhang, Yihe, Cheng, Jiajun, Teng, Kaixuan, Chen, Yunfan, Shi, Jing, Wang, Danlei, Wang, Long, You, Shaohua, Feng, Zeguo, and An, Qi
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- 2024
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17. Effect of dynamic strain aging and precipitation on the hot deformation behavior of 253MA heat-resistant alloy
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Cao, Yu, Zhang, Chenghang, Zhang, Cheng, Wen, Yu, Li, Qian, Wang, Danlei, Huang, Guangjie, and Liu, Qing
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- 2019
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18. Preparation and Utilization of a Comb‐Like Polycarboxylate Dispersant for Organic Pigment.
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Cao, Xinjie, Cai, Zhenyu, Huang, Yifei, Wang, Danlei, Zhang, Lei, and Huang, Kai
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ORGANIC dyes ,NUCLEAR magnetic resonance ,PARTICLE size distribution ,MALEIC anhydride ,NANOPARTICLE size ,POLYETHYLENE glycol - Abstract
As a novel form of carboxylate comb‐like copolymers, SAM‐(m)PEG was prepared by polymerizing styrene (S), acrylic (A), and maleic anhydride (M) to obtain a random copolymer labeled SAM. SAM was then esterified using either polyethylene glycol (PEG) or methyl PEG (mPEG), a waterborne polymer dispersant for dispersing and stabilizing C.I. Pigment Yellow 180 (PY 180). The structures of SAM‐(m)PEG and the ground suspension of PY 180 were characterized by Fourier transform infrared (FT‐IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), a nanoparticle size analysis, and viscometry. The effects of different branch chains, synthetic formulas, and grinding conditions on the dispersibility of SAM‐(m)PEG were evaluated. In addition, the optical properties of the pigments were investigated after ultrafine grinding. The adsorption mechanism between the SAM‐(m)PEG dispersants and PY 180 particles is also discussed. SAM‐PEG6002 outperformed the other SAM‐(m)PEG dispersants owing to its excellent dispersion and stability. When used as the dispersant, the average particle size (Z‐average) of PY 180 after grinding was 264.6 nm, and the particle size distribution became narrow (PDI=0.089). Moreover, SAM‐PEG6002 effectively maintained the color performance of the pigment, and the product was successfully applied to the pigment coating. Therefore, SAM‐PEG6002 is an effective waterborne polymer dispersant for organic pigments. [ABSTRACT FROM AUTHOR]
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- 2023
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19. The Effect of Mn, Al Doping on the CO2 Hydrogenation Performance of CaCO3‐Supported Fe‐Based Catalysts.
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Cai, Zhenyu, Zhang, Fenglei, Cao, Xinjie, Huang, Yifei, Wang, Danlei, Zhang, Lei, and Huang, Kai
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ATMOSPHERIC carbon dioxide ,CATALYSTS ,GREENHOUSE effect ,CATALYST supports ,X-ray diffraction ,HETEROGENEOUS catalysis - Abstract
With increasingly serious environmental problems caused by the greenhouse effect, it has also become essential to reduce the concentration of CO2 in the atmosphere. In this paper, CaCO3‐supported Fe‐based catalysts doped with Mn, Al, and K are prepared by a straightforward method and used for CO2 hydrogenation. The fresh and spent catalysts were characterized by SEM‐EDS, BET, TG, CO2‐TPD, XRD, and XPS. The experimental results show that the highest CO2 conversion rate of Fe10Mn2Al10Ca is 35.99 %, the maximum FTY value is 293.98 μmolCO2 ⋅ gFe-1 ${{\rm{g}}_{{\rm{Fe}}}^{ - 1} }$ ⋅ s−1, the maximum O/P value is 6.61, and the lowest CO selectivity is 32.21 %. At the same time, according to the characterization results, the doping of Mn and Al increased the Fe3O4/FeCx ratio. As the Fe3O4/FeCx ratio increases, the proportion of short‐chain hydrocarbons (CH4, C2–4) in the products increases, and the proportion of long‐chain hydrocarbons (C5+) decrease. Therefore, the co‐doping of Mn and Al promotes the conversion of CO and reduces its selectivity, and promotes the formation of light olefins. Finally, it is hoped that this study can provide a reference for further research on CaCO3‐supported Fe catalysts. [ABSTRACT FROM AUTHOR]
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- 2023
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20. The role of receptor‐mediated activities of 4‐ and 5‐ring unsubstituted and methylated polycyclic aromatic hydrocarbons (PAHs) in developmental toxicity.
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Fang, Jing, Wang, Danlei, Kramer, Nynke I., Rietjens, Ivonne M. C. M., Boogaard, Peter J., and Kamelia, Lenny
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RETINOIC acid receptors ,ARYL hydrocarbon receptors ,POLYCYCLIC aromatic hydrocarbons ,FULVESTRANT ,ANTHRACENE - Abstract
The present study evaluated the aryl hydrocarbon receptor (AhR), estrogen receptor‐α (ER‐α), and retinoic acid receptor (RAR) mediated activities of nine 4‐ and 5‐ring unsubstituted and monomethylated polycyclic aromatic hydrocarbons (PAHs) using a series of Chemical‐Activated LUciferase gene eXpression (CALUX) assays. The potential role of these aforementioned receptors in relation to the developmental toxicity of these PAHs was further assessed in the zebrafish embryotoxicity test (ZET). The results show that all nine tested PAHs were AhR agonists, benz[a]anthracene (BaA) and 8‐methyl‐benz[a]anthracene (8‐MeBaA) were ER‐α agonists, and none of the tested PAHs induced ER‐α antagonistic or RAR (ant)agonistic activities. In the AhR CALUX assay, all the methylated PAHs showed higher potency (lower EC50) in activating the AhR than their respective unsubstituted PAHs, implying that the addition of a methyl substituent on the aromatic ring of PAHs could enhance their AhR‐mediated activities. Co‐exposure of zebrafish embryos with each individual PAH and an AhR antagonist (CH223191) counteracted the observed developmental retardations and embryo lethality to a certain extent, except for 8‐methyl‐benzo[a]pyrene (8‐MeBaP). Co‐exposure of zebrafish embryos with either of the two estrogenic PAHs (i.e., BaA and 8‐MeBaA) and an ER‐α antagonist (fulvestrant) neutralized embryo lethality induced by 50 μM BaA and the developmental retardations induced by 15 μM 8‐MeBaA. Altogether, our findings suggest that the observed developmental retardations in zebrafish embryos by the PAH tested may partially be AhR‐ and/or ER‐α‐mediated, whereas the RAR seems not to be relevant for the PAH‐induced developmental toxicity in the ZET. Our previous study evaluated the in vitro developmental toxicity induced by 4‐ and 5‐ring unsubstituted and methylated polycyclic aromatic hydrocarbons (PAHs) using the zebrafish embryotoxicity test (ZET). The present study further investigated the potential role of the aryl hydrocarbon receptor (AhR), estrogen receptor‐α (ER‐α), and retinoic acid receptor (RAR) in PAH‐induced developmental toxicity. The results show that the PAH‐induced developmental toxicity observed in the ZET may partially be AhR‐ and/or ER‐α‐mediated, whereas the RAR appears not to be involved. [ABSTRACT FROM AUTHOR]
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- 2023
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21. The Effect Of Ca Doping On The CO2 Hydrogenation Performance Of CaxZn10‐xFe20 Catalysts (x=0, 0.5, 1 and1.5).
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Cai, Zhenyu, Zhang, Fenglei, Cao, Xinjie, Huang, Yifei, Wang, Danlei, Zhang, Lei, and Huang, Kai
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CARBON dioxide ,CATALYSTS ,X-ray diffraction ,COPRECIPITATION (Chemistry) ,METHANE - Abstract
In this paper, CaxZn10‐xFe20 catalysts were prepared by the co‐precipitation method and applied to CO2 hydrogenation. The experimental results show that the CO2 conversion of the catalyst Ca1Zn9Fe20 at a Ca doping amount of 1 mmol can reach 57.91 %, which is 13.5 % more than the CO2 conversion of the catalyst Zn10Fe20. Moreover, the catalyst Ca1Zn9Fe20 has the lowest selectivity for both CO and CH4, with 7.40 % and 6.99 %, respectively. The catalysts were characterized by XRD, N2 adsorption‐desorption, CO2‐TPD, H2‐TPR, and XPS. The results demonstrate that the doping of Ca increases the basic sites on the catalyst surface and thus allows the catalyst to adsorb more CO2 to promote the reaction. Besides, the Ca doping amount of 1 mmol can suppress the formation of graphitic carbon on the catalyst surface and prevent the excess graphitic carbon from covering the active site Fe5C2. [ABSTRACT FROM AUTHOR]
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- 2023
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22. Eccentricity paced paleoenvironment evolution and microbial community structure in the Gulf of Mexico during the outgoing Early Eocene Climate Optimum
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Wang, Danlei, Schwark, Lorenz, Ruebsam, Wolfgang, Holman, Alex I., Böttcher, Michael E., Idiz, Erdem, Coolen, Marco J.L., and Grice, Kliti
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- 2022
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23. Study on preparation and performance of advanced nano‐modified epoxy asphalt.
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Wang, Danlei, Zhang, Fenglei, Huang, Kai, and Zhang, Lei
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MULTIWALLED carbon nanotubes ,EPOXY resins ,TENSILE tests ,CARBON nanotubes ,FRACTURE toughness ,MICROSCOPY ,ASPHALT - Abstract
The rapid growth in traffic volume and loads has increased the demand for high strength and durability paving materials. As the primary paving material of long‐life pavements and long‐span steel bridge decks, epoxy asphalt (EA) has the problems of poor tensile strength and low fracture toughness. In this study, graphene oxide nanosheets (GOs) and multiwalled carbon nanotubes (CNTs) were used to improve the mechanical properties of EA. Tensile tests, segregation experiments, Fourier transform infrared analysis, X‐ray diffraction, and fluorescence microscope (FM) were used to analyze the mechanical properties and micromorphology of nano‐modified EA, and to explore the optimal content of these two nano‐modifiers in EA. The results of tensile properties tests show the tensile properties of advanced nano‐modified EA are better when 0.01 wt% CNTs and 0.02 wt% GOs are added. Among them, EA modified by CNTs has the best toughening effect, and its fracture toughness is increased by 21%. Finally, combining macroscopic and microscopic experimental analysis, it is concluded that the mechanical homogeneity of the advanced nano‐modified EA is better, and the asphalt is uniformly dispersed in the continuous phase of epoxy resin. Furthermore, CNTs are chemically reacted with the amino group in oleylamine and modified EA through fiber network reinforcement, and GOs modified EA through the amidation reaction with oleylamine. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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24. Ammonium pyrrolidinedithiocarbamate-modified activated carbon micro-column extraction for the determination of As(III) in water by graphite furnace atomic absorption spectrometry
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Jiang, Yinyan, Wu, Yiwei, Liu, Jungfeng, Xia, Xinquan, and Wang, Danlei
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- 2008
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25. Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro–in silico approach.
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Wang, Danlei, Rietdijk, Maartje H., Kamelia, Lenny, Boogaard, Peter J., and Rietjens, Ivonne M. C. M.
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POLYCYCLIC aromatic hydrocarbons , *PYRENE , *EMBRYONIC stem cells , *ZEBRA danio embryos , *TOXICITY testing , *RATS , *EXPOSURE dose , *ANIMAL experimentation - Abstract
Developmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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26. An End-to-End Rumor Detection Model Based on Feature Aggregation.
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Ye, Aoshuang, Wang, Lina, Wang, Run, Wang, Wenqi, Ke, Jianpeng, and Wang, Danlei
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SOCIAL networks ,DEEP learning ,RUMOR ,NATURAL language processing ,MACHINE learning ,FEATURE selection - Abstract
The social network has become the primary medium of rumor propagation. Moreover, manual identification of rumors is extremely time-consuming and laborious. It is crucial to identify rumors automatically. Machine learning technology is widely implemented in the identification and detection of misinformation on social networks. However, the traditional machine learning methods profoundly rely on feature engineering and domain knowledge, and the learning ability of temporal features is insufficient. Furthermore, the features used by the deep learning method based on natural language processing are heavily limited. Therefore, it is of great significance and practical value to study the rumor detection method independent of feature engineering and effectively aggregate heterogeneous features to adapt to the complex and variable social network. In this paper, a deep neural network- (DNN-) based feature aggregation modeling method is proposed, which makes full use of the knowledge of propagation pattern feature and text content feature of social network event without feature engineering and domain knowledge. The experimental results show that the feature aggregation model has achieved 94.4% of accuracy as the best performance in recent works. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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27. An Easy‐to‐Fabricate Hydrogel Platform with Tunable Stiffness and Cell Anchorage: Validation of Its Feasibility in Modulating Sonic Hedgehog Signaling Pathway Physically.
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Yu, Tingting, Hu, Ke, Xu, Qiufan, Xu, Xueqin, Du, Chunyue, Zhao, Yinyi, Yan, Sen, Wang, Wei, Tang, Shijia, Yue, Shen, Zhang, Xiya, Wang, Danlei, Zhang, Feimin, Cheng, Steven Yan, and Gu, Ning
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FOCAL adhesion kinase ,INTEGRINS ,STIFFNESS (Engineering) ,ANCHORAGE ,EXTRACELLULAR matrix ,MOLECULAR biology ,CELL physiology - Abstract
The biophysical factors of microenvironments have increasingly been recognized as playing key roles in driving cell functions along with biochemical cues. However, current synthetic extracellular matrix materials with tunable biophysical properties are both costly and technically complicated to prepare, therefore limiting their application in the molecular biology field. Herein, an interpenetration hydrogel group with gradient stiffness and cell anchor points is developed, and the matrix stiffness and adhesion property functions as key regulators to determine the final output of Sonic Hedgehog (Shh) signaling is reported. Specifically, it is shown that the spreading areas of mouse embryonic fibroblasts are mainly regulated by stiffness of the matrix. The Shh‐induced Gli1 expression also increases with the cell spreading area. Finally, this work shows that b1‐integrin and focal adhesion kinase, respectively, act as sensors of matrix stiffness and adhesion properties, demonstrating the significance of the precise regulation of Shh signaling by cellular microenvironments. These results demonstrate the feasibility of using this hydrogel platform to study the impact of biophysical changes of the microenvironment on particular cellular signal pathways, and can potentially be applied in low‐cost, high throughput screening of signal pathways which are responsive to the biophysical changes of microenvironments. [ABSTRACT FROM AUTHOR]
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- 2020
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28. PD-linked CHCHD2 mutations impair CHCHD10 and MICOS complex leading to mitochondria dysfunction.
- Author
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Zhou, Wei, Ma, Dongrui, Sun, Alfred Xuyang, Tran, Hoang-Dai, Ma, Dong-liang, Singh, Brijesh K, Zhou, Jin, Zhang, Jinyan, Wang, Danlei, Zhao, Yi, Yen, Paul M, Goh, Eyleen, and Tan, Eng-King
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- 2019
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29. Direct Induction and Functional Maturation of Forebrain GABAergic Neurons from Human Pluripotent Stem Cells.
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Sun, Alfred Xuyang, Yuan, Qiang, Tan, Shawn, Xiao, Yixin, Wang, Danlei, Khoo, Audrey Tze Ting, Sani, Levena, Tran, Hoang-Dai, Kim, Paul, Chiew, Yong Seng, Lee, Kea Joo, Yen, Yi-Chun, Ng, Huck Hui, Lim, Bing, and Je, Hyunsoo Shawn
- Abstract
Summary Gamma-aminobutyric acid (GABA)-releasing interneurons play an important modulatory role in the cortex and have been implicated in multiple neurological disorders. Patient-derived interneurons could provide a foundation for studying the pathogenesis of these diseases as well as for identifying potential therapeutic targets. Here, we identified a set of genetic factors that could robustly induce human pluripotent stem cells (hPSCs) into GABAergic neurons (iGNs) with high efficiency. We demonstrated that the human iGNs express neurochemical markers and exhibit mature electrophysiological properties within 6–8 weeks. Furthermore, in vitro, iGNs could form functional synapses with other iGNs or with human-induced glutamatergic neurons (iENs). Upon transplantation into immunodeficient mice, human iGNs underwent synaptic maturation and integration into host neural circuits. Taken together, our rapid and highly efficient single-step protocol to generate iGNs may be useful to both mechanistic and translational studies of human interneurons. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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30. Correlations between biomarkers of varying bioavailability and putative hydrocarbonoclastic bacteria in an Early-Eocene marlstone sedimentary record.
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Wang, Danlei, Coolen, Marco J.L., Idiz, Erdem, Holman, Alex I., Hopper, Peter, Cockell, Charles S., and Grice, Kliti
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PEARSON correlation (Statistics) , *DENITRIFICATION , *SEDIMENTARY rocks , *BIOMARKERS , *REFRIGERATED storage , *EOCENE Epoch - Abstract
We examined the possibility that, during short-term refrigerated storage, microbial communities continue to biodegrade individual lipid biomarkers in an intact core section of Early Eocene consolidated marlstone sediments from the hydrothermal system overlying the Chicxulub impact crater (Yucatán, Mexico). Amplicon sequencing of environmental 16S rRNA obtained from the core samples revealed a high relative abundance of amplicon sequence variants (ASVs) related to known hydrocarbon degraders, notably Halomonas and Marinobacter. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) predicted that Marinobacter and a subset of less abundant bacteria (e.g., Alcanivorax) have the genomic potential to anaerobically degrade hydrocarbons via dissimilatory nitrate reduction to ammonia. The variability in the relative abundance of these taxa showed strong positive Pearson correlations (Pearson's r > 0.5) with quantitative changes in the most bioavailable non-sulfurized compounds, notably polycyclic aromatic hydrocarbons (PAHs) and isorenieratane. Moderate positive Pearson correlations (r values between ∼0.3 and ∼0.5) were observed between microbial taxa and compounds that have undergone early abiotic diagenetic sulfurization (e.g., hopanes, n -alkanes and steranes). These results suggest that non-sulfurized biomarkers may be subject to continued biodegradation in marine sedimentary rocks during short-term refrigerated storage. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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31. In vitro metabolism of naphthalene and its alkylated congeners by human and rat liver microsomes via alkyl side chain or aromatic oxidation.
- Author
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Wang, Danlei, Bruyneel, Ben, Kamelia, Lenny, Wesseling, Sebastiaan, Rietjens, Ivonne M.C.M., and Boogaard, Peter J.
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LIVER microsomes , *NAPHTHALENE derivatives , *NAPHTHALENE , *POLYCYCLIC aromatic hydrocarbons , *MINERAL oils , *BIOTRANSFORMATION (Metabolism) - Abstract
Mineral oils are widely applied in food production and processing and may contain polycyclic aromatic hydrocarbons (PAHs). The PAHs that may be present in mineral oils are typically alkylated, and have been barely studied. Metabolic oxidation of the aromatic ring is a key step to form DNA-reactive PAH metabolites, but may be less prominent for alkylated PAHs since alkyl substituents would facilitate side chain oxidation as an alternative. The current study investigates this hypothesis of preferential side chain oxidation at the cost of aromatic oxidation using naphthalene and a series of its alkyl substituted analogues as model compounds. The metabolism was assessed by measuring metabolite formation in rat and human liver microsomal incubations using UPLC and GC-MS/MS. The presence of an alkyl side chain markedly reduced aromatic oxidation for all alkyl-substituted naphthalenes that were converted. 1-n-Dodecyl-naphthalene was not metabolized under the experimental conditions applied. With rat liver microsomes for 1-methyl-, 2-methyl-, 1-ethyl-, and 2-ethyl- naphthalene, alkyl side chain oxidation was preferred over aromatic oxidation. With human liver microsomes this was the case for 2-methyl-, and 2-ethyl-naphthalene. It is concluded that addition of an alkyl substituent in naphthalene shifts metabolism in favor of alkyl side chain oxidation at the cost of aromatic ring oxidation. Furthermore, alkyl side chains of 6 or more carbon atoms appeared to seriously hamper and reduce overall metabolism, metabolic conversion being no longer observed with the C12 alkyl side chain. In summary, alkylation of PAHs likely reduces their chances of aromatic oxidation and bioactivation. • Alkyl substitution of naphthalene shifts metabolism in favor of alkyl side chain oxidation at the cost of aromatic ring oxidation. • Metabolism and bioactivation of naphthalene is hampered when the alkyl substituent contains over 6 carbon atoms. • Alkylation of PAHs likely reduces their chances on aromatic oxidation and potential bioactivation. [ABSTRACT FROM AUTHOR]
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- 2020
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32. Upregulated hexokinase 2 expression induces the apoptosis of dopaminergic neurons by promoting lactate production in Parkinson's disease.
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Li, Jingyi, Chen, Longmin, Qin, Qixiong, Wang, Danlei, Zhao, Jingwei, Gao, Hongling, Yuan, Xiao, Zhang, Jing, Zou, Yuan, Mao, Zhijuan, Xiong, Yongjie, Min, Zhe, Yan, Manli, Wang, Cong-yi, and Xue, Zheng
- Subjects
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DOPAMINERGIC neurons , *LACTATES , *PARKINSON'S disease , *RAPAMYCIN , *GLUCOKINASE , *MONOCARBOXYLATE transporters , *LACTATION , *APOPTOSIS , *DOPAMINE receptors - Abstract
Parkinson's disease (PD) is characterized by impaired mitochondrial function and decreased ATP levels. Aerobic glycolysis and lactate production have been shown to be upregulated in dopaminergic neurons to sustain ATP levels, but the effect of upregulated glycolysis on dopaminergic neurons remains unknown. Since lactate promotes apoptosis and α-synuclein accumulation in neurons, we hypothesized that the lactate produced upon upregulated glycolysis is involved in the apoptosis of dopaminergic neurons in PD. In this study, we examined the expression of hexokinase 2 (HK2) and lactate dehydrogenase (LDH), the key enzymes in glycolysis, and lactate levels in the substantia nigra pars compacta (SNpc) of a MPTP-induced mouse model of PD and in MPP+-treated SH-SY5Y cells. We found that the expression of HK2 and LDHA and the lactate levels were markedly increased in the SNpc of MPTP-treated mice and in MPP+-treated SH-SY5Y cells. Exogenous lactate treatment led to the apoptosis of SH-SY5Y cells. Intriguingly, lactate production and the apoptosis of dopaminergic neurons were suppressed by the application of 3-bromopyruvic acid (3-Brpa), a HK2 inhibitor, or siRNA both in vivo and in vitro. 3-Brpa treatment markedly improved the motor behaviour of MPTP-treated mice in pole test and rotarod test. Mechanistically, lactate increases the activity of adenosine monophosphate-activated protein kinase (AMPK) and suppresses the phosphorylation of serine/threonine kinase 1 (Akt) and mammalian target of rapamycin (mTOR). Together, our data suggest that upregulated HK2 and LDHA and increased lactate levels prompt the apoptosis of dopaminergic neurons in PD. Inhibition of HK2 expression attenuated the apoptosis of dopaminergic neurons by downregulating lactate production and AMPK/Akt/mTOR pathway in PD. [Display omitted] • Aerobic glycolysis has been shown to be upregulated in PD, but the effect on dopaminergic neurons remains unknown. • Upregulated HK2 and LDHA and increased lactate are involved in the apoptosis of dopaminergic neurons. • Pharmacological suppression or genetic ablation of HK2 alleviated the apoptosis of dopaminergic neurons. • Our findings provide new insight into the pathological mechanisms underlying the pros and cons of glycolysis in PD. [ABSTRACT FROM AUTHOR]
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- 2022
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33. CCL5 promotes LFA-1 expression in Th17 cells and induces LCK and ZAP70 activation in a mouse model of Parkinson's disease.
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Zhao J, An K, Mao Z, Qu Y, Wang D, Li J, Min Z, and Xue Z
- Abstract
Background: Parkinson's disease (PD), which is associated to autoimmune disorders, is characterized by the pathological deposition of alpha-synuclein (α-Syn) and loss of dopaminergic (DA) neurons. Th17 cells are thought to be responsible for the direct loss of DA neurons. C-C chemokine ligand 5 (CCL5) specifically induces Th17 cell infiltration into the SN. However, the specific effect of CCL5 on Th17 cells in PD and the relationship between CCL5 and lymphocyte function-associated antigen-1 (LFA-1) expression in Th17 cells are unknown., Methods: We evaluated the effects of CCL5 on LFA-1 expression in Th17 cells in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and examined Th17 cell differentiation upon CCL5 stimulation in vitro . Furthermore, we assessed the effects of CCL5 on tyrosine kinase zeta-chain-associated protein kinase 70 (ZAP70) and lymphocyte-specific protein tyrosine kinase (LCK) activity in CCL5-stimulated Th17 cells in vivo and in vitro ., Results: CCL5 increased the proportion of peripheral Th17 cells in MPTP-treated mice, LFA-1 expression on Th17 cells, and Th17 cell levels in the SN of MPTP-treated mice. CCL5 promoted Th17 cell differentiation and LFA-1 expression in naive T cells in vitro . Moreover, CCL5 increased Th17 cell differentiation and LFA-1 expression by stimulating LCK and ZAP70 activation in naive CD4
+ T cells. Inhibiting LCK and ZAP70 activation reduced the proportion of peripheral Th17 cells and LFA-1 surface expression in MPTP-treated mice, and Th17 cell levels in the SN also significantly decreased., Conclusion: CCL5, which increased Th17 cell differentiation and LFA-1 protein expression by activating LCK and ZAP70, could increase the Th17 cell number in the SN, induce DA neuron death and aggravate PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, An, Mao, Qu, Wang, Li, Min and Xue.)- Published
- 2023
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34. THE EFFECT OF Mn, Al DOPING ON THE CO2 HYDROGENATION PERFORMANCE OF CaCO3-SUPPORYED Fe-BASED CATALYSTS.
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Cai Z, Zhang F, Cao X, Huang Y, Wang D, Zhang L, and Huang K
- Abstract
With increasingly serious environmental problems caused by the greenhouse effect, it has also become essential to reduce the concentration of CO2 in the atmosphere. In this paper, CaCO3-supported Fe-based catalysts doped with Mn, Al, and K are prepared by a straightforward method and used for CO2 hydrogenation. The fresh and spent catalysts were characterized by SEM-EDS, BET, TG, CO2-TPD, XRD, and XPS. The experimental results show that the highest CO2 conversion rate of Fe10Mn2Al10Ca is 35.99%, the maximum FTY value is 293.98 μmolCO2·g-1 Fe·s-1, the maximum O/P value is 6.61, and the lowest CO selectivity is 32.21%. At the same time, according to the characterization results, the doping of Mn and Al increased the Fe3O4/FeCx ratio. As the Fe3O4/FeCx ratio increases, the proportion of short-chain hydrocarbons (CH4, C2-4) in the products increases, and the proportion of long-chain hydrocarbons (C5+) decrease. Therefore, the co-doping of Mn and Al promotes the conversion of CO and reduces its selectivity, and promotes the formation of light olefins. Finally, it is hoped that this study can provide a reference for further research on CaCO3-supported Fe catalysts., (© 2023 Wiley-VCH GmbH.)
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- 2023
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35. The Effect Of Ca Doping On The CO2 Hydrogenation Performance Of CaxZn10-xFe20 Catalysts (x=0, 0.5, 1 and1.5).
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Cai Z, Zhang F, Cao X, Huang Y, Wang D, Zhang L, and Huang K
- Abstract
In this paper, CaxZn10-xFe20 catalysts were prepared by the co-precipitation method and applied to CO
2 hydrogenation. The experimental results show that the CO2 conversion of the catalyst Ca1Zn9Fe20 at a Ca doping amount of 1 mmol can reach 57.91 %, which is 13.5 % more than the CO2 conversion of the catalyst Zn10Fe20. Moreover, the catalyst Ca1Zn9Fe20 has the lowest selectivity for both CO and CH4, with 7.40 % and 6.99 %, respectively. The catalysts were characterized by XRD, N2 adsorption-desorption, CO2 -TPD, H2 -TPR, and XPS. The results demonstrate that the doping of Ca increases the basic sites on the catalyst surface and thus allows the catalyst to adsorb more CO2 to promote the reaction. Besides, the Ca doping amount of 1 mmol can suppress the formation of graphitic carbon on the catalyst surface and prevent the excess graphitic carbon from covering the active site Fe5 C2 ., (© 2023 Wiley-VCH GmbH.)- Published
- 2023
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36. Feasibility and basic acoustic characteristics of intelligent long-term bowel sound analysis in term neonates.
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Zhou P, Lu M, Chen P, Wang D, Jin Z, and Zhang L
- Abstract
Objective: Bowel dysfunction continues to be a serious issue in neonates. Traditional auscultation of bowel sounds as a diagnostic tool in neonatal gastrointestinal problems is limited by skill and inability to document and reassess. Consequently, in order to objectively and noninvasively examine the viability of continuous assessment of bowel sounds, we utilized an acoustic recording and analysis system to capture bowel sounds and extract acoustic features in term neonates., Methods: From May 1, 2020 to September 30, 2020, 82 neonates who were hospitalized because of hyperbilirubinemia were included. For 20 h, a convolutional neural network-based acoustic recorder that offers real-time, wireless, continuous auscultation was employed to track the bowel sounds of these neonates., Results: (1) Usable data on five acoustic parameters of bowel sound was recorded for 68 neonates, and the median values were as follows: The rate was 25.80 times/min [interquartile range (IQR): 15.63-36.20]; the duration was 8.00 s/min (IQR: 4.2-13.20); the amplitude was 0.46 (IQR: 0.27-0.68); the frequency was 944.05 Hz (IQR: 848.78-1,034.90); and the interval time was 2.12 s (IQR: 1.3-3.5). (2) In comparison to the parameters of the bowel sounds recorded from the right lower abdomen in 68 infants, the acoustic parameters of the 10 out of 68 infants from chest controls and blank controls were considerably different. (3) The 50%-75% breast milk intake group had the highest rate, the longest duration, and the highest amplitude of bowel sounds, while the >75% breast milk intake group had the highest frequency of bowel sounds. (4) Compared with neonates without hyperbilirubinemia, there was no significant difference in the five parameters of bowel sounds in hyperbilirubinemia infants; nor was there a significant effect of phototherapy and non-phototherapy status on the parameters of bowel sounds during bowel sound monitoring in hyperbilirubinemia patients. (5) A mild transient skin rash appeared on the skin of three infants. No other adverse events occurred., Conclusion: The acoustic recording and analysis system appears useful for monitoring bowel sounds using a continuous, invasive, and real-time approach. Neonatal bowel sounds are affected by various feeding types rather than hyperbilirubinemia and phototherapy. Potential influencing factors and the significance of their application in neonatal intestinal-related disorders require further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Zhou, Lu, Chen, Wang, Jin and Zhang.)
- Published
- 2022
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37. Traditional Chinese medicine for promoting mental health of patients with COVID-19: a scoping review.
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Ji Z, Hu H, Wang D, Di Nitto M, Fauci AJ, Okada M, Li K, and Wang H
- Abstract
This study aimed to systematically review and depict the current studies of traditional Chinese medicine for the mental health of patients with coronavirus disease 2019 (COVID-19)., Methods: A scoping review was conducted by searching PubMed, Web of Science, CNKI, Wanfang database, VIP database, and SinoMed, with the retrieval time being from the establishment of the database to April 18, 2022. The basic information of the included studies, objective, design, types of patients, interventions, outcomes, etc., was reviewed and summarized narratively. Methodological quality was assessed using the Cochrane Risk of Bias assessment tool, the methodological index for non-randomized studies or the Newcastle-Ottawa scale., Results: We identified 30 traditional Chinese medicine (TCM) studies from six databases. Among them, finished randomized controlled trials ( n = 16) accounted for most of the studies, followed by single-arm studies (n = 9). In terms of study theme, 20 studies defined the mental health of patients with COVID-19 as the research theme. Psychological assessment was included in the inclusion criteria (performed before participation) of nine studies, whereas the other studies only mentioned the mental outcomes. TCM interventions included TCM exercises (Yijinjing, Baduanjin, Liuzijue, Taichi), acupoint stimulation (auricular and body points), moxibustion, decoction, or granules based on TCM syndrome differentiation, decoction, or granules with fixed formulae (Baidu Jieduan granules, Xuanfei Baidu decoction, and Qingfei Paidu decoction), Chinese patent medicine (Jinhua Qinggan granules), TCM psychological therapy (TCM ideological therapy, TCM five-tone therapy, and TCM psychological sand table), and TCM nursing (dialectical care, dialectical diet, and psychological counseling). Anxiety and depression were the main outcomes evaluated in regard to mental health in patients with COVID-19. The limitations of methodological quality were predominantly from follow-up, blinding, and registration. Positive results were reported by 27 studies (90%, n = 30)., Conclusion: We summarized the existing literature about the impact of TCM on mental health in patients with COVID-19. The number of studies evaluating the impact of TCM on mental health is encouraging, but overall methodological quality was low. Several TCM interventions warrant further evaluation, particularly among populations outside of China, for the purpose of establishing supporting evidence. More importantly, research with stronger methodological quality needs to be developed., Graphical Abstract: http://links.lww.com/AHM/A36., Competing Interests: This article only represents the authors’ personal opinions, and does not represent any involvement of the bodies or authorities of affiliation. All authors have not received any fee or reimbursement for participating in the study and writing this article., (Copyright © 2022 Tianjin University of Traditional Chinese Medicine.)
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- 2022
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38. The Association of CSF sTREM2 With Cognitive Decline and Its Dynamic Change in Parkinson's Disease: Analysis of the PPMI Cohort.
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Qin Q, Wan H, Wang D, Li J, Qu Y, Zhao J, Li J, and Xue Z
- Abstract
Background: Soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) is a biomarker of microglial activation and increased in several neurodegenerative diseases. However, the role of sTREM2 in Parkinson's diseases (PDs) remains unclear. This study aims to investigate whether CSF sTREM2 is changed during the pathology of PD and its association with cognitive decline., Methods: We recruited 219 de novo patients with PD and 100 healthy controls from Parkinson's Progression Markers Initiative (PPMI). Cross-sectional and longitudinal associations between cognition and CSF sTREM2 were evaluated using multivariable-adjusted models. To assess the changes in CSF sTREM2 during the pathology of PD, patients were classified through the A/T classification framework with addition of α-synuclein (α-syn), which we implemented based on the CSF amyloid β-peptide
1-42 (A) and phosphorylated tau (T) and α-syn (S)., Results: The CSF sTREM2 did not differ between healthy controls and patients with PD or between PD clinical subgroups ( p > 0.05). However, higher baseline CSF sTREM2 predicted greater global cognitive decline in patients with PD (β = -0.585, p = 0.039). Moreover, after a mean follow-up of 5.51 ± 1.31 years, baseline CSF sTREM2 that elevated in the middle tertile (HR = 2.426, 95% CI: 1.023-5.754, p = 0.044) and highest tertile (HR = 2.833, 95% CI: 1.226-6.547, p = 0.015) were associated with a future high risk of cognitive decline. Additionally, CSF sTREM2 decreased in abnormal Aβ pathology (A+) and α-syn pathology (S+) but normal tau pathology, while increased in abnormal phosphorylated tau (T+) ( p < 0.05)., Conclusion: CSF sTREM2 may be a promising predictor for the cognitive decline in PD rather than a diagnostic biomarker. The dynamic change in CSF sTREM2 in PD may help to the monitor of neuronal injury and microglial activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Wan, Wang, Li, Qu, Zhao, Li and Xue.)- Published
- 2022
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39. Effect of Cerebral Microbleeds on Cognitive Function and Quality of Life in Parkinson Disease.
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Qin Q, Wan H, Wang D, Li J, Yang Q, Zhao J, and Xue Z
- Subjects
- Female, Follow-Up Studies, Humans, Male, Middle Aged, Neuropsychological Tests, Parkinson Disease physiopathology, Retrospective Studies, Brain blood supply, Cerebrovascular Circulation physiology, Cognition physiology, Magnetic Resonance Imaging methods, Parkinson Disease diagnosis, Quality of Life
- Abstract
BACKGROUND This study aimed to investigate the risk factors and patterns of cerebral microbleeds (CMBs) in Parkinson disease (PD) and the impact of CMBs on cognitive function and quality of life (QoL). MATERIAL AND METHODS Patients with PD that underwent susceptibility-weighted imaging were recruited and divided into CMB-free, lobar-CMB, deep-CMB, and mixed-CMB groups according to CMB location. Motor function (MDS-UPDRS III), cognitive abilities (MoCA, MMSE), and QoL (PDQ-39) were compared among groups. The risk factors for CMBs in patients with PD and the association between CMBs and cognition and QoL were analyzed using multivariable logistic regression models and linear regression models. RESULTS Among the 209 patients with PD, 42 (20.1%) had CMBs. Lobar, deep, and mixed CMBs were observed in 15 (35.7%), 17 (40.5%), and 10 (23.8%) patients, respectively. A higher frequency of hypertension was independently associated with deep CMBs (odds ratio [OR]=4.379, 95% CI: 1.405-13.643, P=0.011). The deep-CMB and mixed-CMB groups had lower MoCA scores and MMSE scores than the CMB-free group, especially in domains of naming, attention, and orientation (P<0.05). Additionally, the presence of CMBs was associated with lower MMSE (R²=0.140, ß=-0.301, P<0.001) and MoCA (R²=0.104, ß=-0.289, P<0.001) and higher PDQ-39 (R²=0.052, ß=0.227, P<0.05) scores, while the association between CMBs and PDQ-39 disappeared after adjustment of MMSE or MoCA as a covariate. CONCLUSIONS The results suggest that hypertension was associated with the occurrence of deep CMBs. Comorbidity with CMBs may impair cognitive function and indirectly reduce the QoL in patients with PD.
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- 2022
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40. Potassium channel dysfunction in human neuronal models of Angelman syndrome.
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Sun AX, Yuan Q, Fukuda M, Yu W, Yan H, Lim GGY, Nai MH, D'Agostino GA, Tran HD, Itahana Y, Wang D, Lokman H, Itahana K, Lim SWL, Tang J, Chang YY, Zhang M, Cook SA, Rackham OJL, Lim CT, Tan EK, Ng HH, Lim KL, Jiang YH, and Je HS
- Subjects
- Angelman Syndrome physiopathology, Animals, Epilepsy metabolism, Humans, Mice, Models, Neurological, Neurons drug effects, Neurons metabolism, Organoids, Potassium Channel Blockers pharmacology, Potassium Channel Blockers therapeutic use, Seizures metabolism, Ubiquitin-Protein Ligases genetics, Ubiquitination, Angelman Syndrome metabolism, Calcium Channels, N-Type metabolism, Ubiquitin-Protein Ligases metabolism
- Abstract
Disruptions in the ubiquitin protein ligase E3A ( UBE3A ) gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remains unclear. Using human neurons and brain organoids, we demonstrate that UBE3A suppresses neuronal hyperexcitability via ubiquitin-mediated degradation of calcium- and voltage-dependent big potassium (BK) channels. We provide evidence that augmented BK channel activity manifests as increased intrinsic excitability in individual neurons and subsequent network synchronization. BK antagonists normalized neuronal excitability in both human and mouse neurons and ameliorated seizure susceptibility in an AS mouse model. Our findings suggest that BK channelopathy underlies epilepsy in AS and support the use of human cells to model human developmental diseases., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2019
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41. Sensitive liquid chromatographic assay for the simultaneous determination of ibuprofen and its prodrug, ibuprofen eugenol ester, in rat plasma.
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Zhao X, Chen D, Li K, and Wang D
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- Animals, Calibration, Esters blood, Eugenol blood, Female, Glycyrrhetinic Acid blood, Male, Rats, Rats, Wistar, Reproducibility of Results, Sensitivity and Specificity, Chromatography, High Pressure Liquid methods, Ibuprofen blood, Prodrugs analysis
- Abstract
A rapid, sensitive, and specific reverse-phase high-performance liquid chromatography (HPLC) method was developed to quantitate ibuprofen (IBU) and its prodrug, ibuprofen eugenol ester (IEE), simultaneously in rat plasma. IBU, IEE, and the internal standard glycryrrhetic acid (GA) were detected by UV absorption at 230 nm. Extraction recoveries for all compounds ranged between 82.6% and 96.2%. Retention times of IBU, IEE, and GA were 5.62, 15.98, and 18.05 min, respectively. Calibration plots were linear over the range of 0.64 to 64 microg/ml for IBU, and 0.16 to 80 microg/ml for IEE. The limit of quantitation was 0.64 microg/ml for IBU and 0.16 microg/ml for IEE. The intra- and interday variations were less than 10% and accuracy was greater than 90%. The results showed that the established method is reproducible and sensitive and applicable to plasma samples collected from rats administered IBU and IEE intravenously.
- Published
- 2005
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