78 results on '"Ya Zhuo"'
Search Results
2. Analysis/application of stabilization by the over-integration technique in CBS-SEM for incompressible flow
- Author
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Ximeng Ye, Guoliang Qin, Ya Zhuo, and Miaomiao Li
- Subjects
Computational Mathematics ,Computational Theory and Mathematics ,Modeling and Simulation - Published
- 2022
3. Selective and replicable neuroimaging-based indicators of pain discriminability
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Zhang, Li-Bo, primary, Lu, Xue-Jing, additional, Huang, Gan, additional, Zhang, Hui-Juan, additional, Tu, Yi-Heng, additional, Kong, Ya-Zhuo, additional, and Hu, Li, additional
- Published
- 2022
- Full Text
- View/download PDF
4. A non–GPCR-binding partner interacts with a novel surface on β-arrestin1 to mediate GPCR signaling
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Vsevolod V. Gurevich, Sergey A. Vishnivetskiy, Adriano Marchese, Candice S. Klug, and Ya Zhuo
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0301 basic medicine ,Receptors, CXCR4 ,MAP Kinase Signaling System ,Biochemistry ,Protein Structure, Secondary ,Focal adhesion ,03 medical and health sciences ,Chemokine receptor ,Arrestin ,Humans ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,G protein-coupled receptor ,Endosomal Sorting Complexes Required for Transport ,030102 biochemistry & molecular biology ,Chemistry ,Effector ,Signal transducing adaptor protein ,Chemotaxis ,Cell Biology ,Phosphoproteins ,Chemokine CXCL12 ,Cell biology ,A-site ,HEK293 Cells ,beta-Arrestin 1 ,030104 developmental biology ,Focal Adhesion Kinase 1 ,Signal Transduction - Abstract
The multifaceted adaptor protein β-arr1 (β-arrestin1) promotes activation of focal adhesion kinase (FAK) by the chemokine receptor CXCR4, facilitating chemotaxis. This function of β-arr1 requires the assistance of the adaptor protein STAM1 (signal-transducing adaptor molecule 1) because disruption of the interaction between STAM1 and β-arr1 reduces CXCR4-mediated activation of FAK and chemotaxis. To begin to understand the mechanism by which β-arr1 together with STAM1 activates FAK, we used site-directed spin-labeling EPR spectroscopy-based studies coupled with bioluminescence resonance energy transfer–based cellular studies to show that STAM1 is recruited to activated β-arr1 by binding to a novel surface on β-arr1 at the base of the finger loop, at a site that is distinct from the receptor-binding site. Expression of a STAM1-deficient binding β-arr1 mutant that is still able to bind to CXCR4 significantly reduced CXCL12-induced activation of FAK but had no impact on ERK-1/2 activation. We provide evidence of a novel surface at the base of the finger loop that dictates non-GPCR interactions specifying β-arrestin–dependent signaling by a GPCR. This surface might represent a previously unidentified switch region that engages with effector molecules to drive β-arrestin signaling.
- Published
- 2020
5. Why are There Conflicts of Interest? Investigation of Teacher Exchange within Arts Education Group in China
- Author
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Xue Xia, Yi-Ning Yang, and Ya-Zhuo Xie
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
6. Selective and replicable neuroimaging-based indicators of pain discriminability
- Author
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Li-Bo Zhang, Xue-Jing Lu, Gan Huang, Hui-Juan Zhang, Yi-Heng Tu, Ya-Zhuo Kong, and Li Hu
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Humans ,Brain ,Pain ,Neuroimaging ,Magnetic Resonance Imaging ,General Biochemistry, Genetics and Molecular Biology - Abstract
Neural indicators of pain discriminability have far-reaching theoretical and clinical implications but have been largely overlooked previously. Here, to directly identify the neural basis of pain discriminability, we apply signal detection theory to three EEG (Datasets 1-3, total N = 366) and two fMRI (Datasets 4-5, total N = 399) datasets where participants receive transient stimuli of four sensory modalities (pain, touch, audition, and vision) and two intensities (high and low) and report perceptual ratings. Datasets 1 and 4 are used for exploration and others for validation. We find that most pain-evoked EEG and fMRI brain responses robustly encode pain discriminability, which is well replicated in validation datasets. The neural indicators are also pain selective since they cannot track tactile, auditory, or visual discriminability, even though perceptual ratings and sensory discriminability are well matched between modalities. Overall, we provide compelling evidence that pain-evoked brain responses can serve as replicable and selective neural indicators of pain discriminability.
- Published
- 2022
7. Changes in brain connectivity linked to multisensory processing of pain modulation in migraine with acupuncture treatment
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Liu, Lu, primary, Lyu, Tian-Li, additional, Fu, Ming-Yang, additional, Wang, Lin-Peng, additional, Chen, Ying, additional, Hong, Jia-Hui, additional, Chen, Qiu-Yi, additional, Zhu, Yu-Pu, additional, Tan, Zhong-Jian, additional, Liu, Da-Peng, additional, Chen, Zi-Wei, additional, Kong, Ya-Zhuo, additional, and Li, Bin, additional
- Published
- 2022
- Full Text
- View/download PDF
8. Why are There Conflicts of Interest? Investigation of Teacher Exchange within Arts Education Group in China
- Author
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Xia, Xue, primary, Yang, Yi-Ning, additional, and Xie, Ya-Zhuo, additional
- Published
- 2022
- Full Text
- View/download PDF
9. G protein–coupled receptor kinase phosphorylation of distal C-tail sites specifies βarrestin1-mediated signaling by chemokine receptor CXCR4
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Ya Zhuo, Joseph M. Crecelius, and Adriano Marchese
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Arrestin ,beta-Arrestin 1 ,Arrestins ,Cell Biology ,Phosphorylation ,G-Protein-Coupled Receptor Kinases ,Molecular Biology ,Biochemistry ,beta-Arrestins - Abstract
G protein-coupled receptor (GPCR) kinases (GRKs) and arrestins mediate GPCR desensitization, internalization, and signaling. The spatial pattern of GPCR phosphorylation is predicted to trigger these discrete GRK and arrestin-mediated functions. Here, we provide evidence that distal carboxyl-terminal tail (C-tail), but not proximal, phosphorylation of the chemokine receptor CXCR4 specifies βarrestin1 (βarr1)-dependent signaling. We demonstrate by pharmacologic inhibition of GRK2/3-mediated phosphorylation of the chemokine receptor CXCR4 coupled with site-directed mutagenesis and bioluminescence resonance energy transfer approaches that distal, not proximal, C-tail phosphorylation sites are required for recruitment of the adaptor protein STAM1 (signal-transducing adaptor molecule) to βarr1 and focal adhesion kinase phosphorylation but not extracellular signal-regulated kinase 1/2 phosphorylation. In addition, we show that GPCRs that have similarly positioned C-tail phosphoresidues are also able to recruit STAM1 to βarr1. However, although necessary for some GPCRs, we found that distal C-tail sites might not be sufficient to specify recruitment of STAM1 to βarr1 for other GPCRs. In conclusion, this study provides evidence that distal C-tail phosphorylation sites specify GRK-βarrestin-mediated signaling by CXCR4 and other GPCRs.
- Published
- 2022
10. Paleogeographic evolution of a Carboniferous–Permian sea in the southernmost part of the Central Asian Orogenic Belt, NW China: Evidence from microfacies, provenance and paleobiogeography
- Author
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Niu, Ya-zhuo, primary, Shi, G.R., additional, Ji, Wen-hua, additional, Zhou, Jun-lin, additional, Wang, Jian-qiang, additional, Wang, Kai, additional, Bai, Jian-Ke, additional, and Yang, Bo, additional
- Published
- 2021
- Full Text
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11. Network toxicology and LC-MS-based metabolomics: New approaches for mechanism of action of toxic components in traditional Chinese medicines
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Changxiao Liu, Ya-zhuo Li, Xin Jin, Dan-dan Gao, Rui Liu, and Xinyu Li
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Pharmacology ,Mechanism (biology) ,Chemistry ,030226 pharmacology & pharmacy ,01 natural sciences ,0104 chemical sciences ,Toxicology ,010404 medicinal & biomolecular chemistry ,03 medical and health sciences ,0302 clinical medicine ,Metabolomics ,Complementary and alternative medicine ,Mechanism of action ,Toxicity ,medicine ,Pharmacology (medical) ,medicine.symptom - Abstract
Network toxicology combined with metabonomics is of great significance for the study of the toxic mechanism and prediction of toxicity of traditional Chinese medicines (TCMs). In this study, we reviewed the application of network toxicology based on LC-MS metabolomics, mainly in the study of toxic components and the toxicity mechanism of TCMs, which provides new ideas and methods for the further study of the toxicity mechanism of TCMs.
- Published
- 2019
12. Prediction of quality markers of traditional Chinese medicines based on network pharmacology
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Changxiao Liu, Liang Liu, Yu-li Wang, Maoliang Liao, Tie-jun Zhang, Hongbing Zhang, Tao Cui, Wen-bin Hou, Ya-zhuo Li, and He Huang
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Pharmacology ,Network medicine ,Computer science ,Traditional Chinese medicine ,Complex network ,030226 pharmacology & pharmacy ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,03 medical and health sciences ,0302 clinical medicine ,Complementary and alternative medicine ,Risk analysis (engineering) ,Network pharmacology ,Pharmacology (medical) - Abstract
Network pharmacology is a powerful tool to reflect the pharmacologically active effects, mechanism of action and toxic activity of traditional Chinese medicines (TCMs). The ingredients of TCMs, associated with quality control of TCM products, are those fundamental chemicals that exhibit biological activities. A great amount of effort has been made by scientists in that field in order to improve the quality of TCMs, though the approaches to determine their quality and the TCM theory and compatibility rules remain ambiguous. Now some methods and technologies must be applied to predict and explore the quality marker (Q-marker) for quality control, as well as to clarify the factors affecting the quality of TCM, which may give new insight into rational ground of establishment of appropriate quality control and assessment system. In this review paper, authors focus on the prediction of quality markers of TCMs by network pharmacology based on three aspects: (1) from network medicine to network pharmacology, (2) complex network system of traditional Chinese medicine, and (3) predicting TCM quality markers based on network pharmacology. Authors proposed the research pattern on network pharmacology based on biological and medical networks, and further TCM network pharmacology based on substantial basis of TCM formulae, and the idea of “effect-ingredient-target-fingerprint” to predict and recognize the TCM Q-marker was the ultimate goal. In addition, authors yet noted how to make full use of the advantages of network toxicology to provide new ideas for the toxicity study of complex TCM systems and the prediction of TCM toxicity markers.
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- 2019
13. Low temperature effects on carotenoids biosynthesis in the leaves of green and albino tea plant (Camellia sinensis (L.) O. Kuntze)
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Yang, Ya-Zhuo, primary, Li, Tong, additional, Teng, Rui-Min, additional, Han, Miao-Hua, additional, and Zhuang, Jing, additional
- Published
- 2021
- Full Text
- View/download PDF
14. An integrated approach to uncover quality marker underlying the effects of Alisma orientale on lipid metabolism, using chemical analysis and network pharmacology
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Yanan Zheng, Ya-zhuo Li, Haihua Shang, Miao Wang, Maoliang Liao, Changxiao Liu, Tian Li, and Wen-bin Hou
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Male ,0301 basic medicine ,Evaluation system ,media_common.quotation_subject ,ved/biology.organism_classification_rank.species ,Pharmaceutical Science ,Computational biology ,Biology ,Biomarkers, Pharmacological ,03 medical and health sciences ,Network pharmacology ,Drug Discovery ,Animals ,Humans ,Quality (business) ,Alisma orientale ,Medicine, Chinese Traditional ,Rats, Wistar ,Cholestenones ,Hypolipidemic Agents ,media_common ,Pharmacology ,Plant Extracts ,ved/biology ,Quality assessment ,Lipid metabolism ,Hep G2 Cells ,Integrated approach ,Lipid Metabolism ,Pharmacological action ,030104 developmental biology ,Complementary and alternative medicine ,Alisma ,Molecular Medicine ,Drugs, Chinese Herbal - Abstract
Background Quality control of traditional Chinese medicines is currently a great concern, due to the correlation between the quality control indicators and clinic effect is often questionable. According to the “multi-components and multi-targets” property of TCMs, a new special quality and bioactivity evaluation system is urgently needed. Purpose Present study adopted an integrated approach to provide new insights relating to uncover quality marker underlying the effects of Alisma orientale (AO) on lipid metabolism. Methods In this paper, guided by the concept of the quality marker (Q-marker), an integrated strategies “effect-compound-target-fingerprint” was established to discovery and screen the potential quality marker of AO based on network pharmacology and chemical analysis. Firstly, a bioactivity evaluation was performed to screen the main active fractions. Then the chemical compositions were rapidly identified by chemical analysis. Next, networks were constructed to illuminate the interactions between these component and their targets for lipid metabolism, and the potential Q-marker of AO was initially screened. Finally, the activity of the Q-markers was validated in vitro. Results 50% ethanol extract fraction was found to have the strongest lipid-lowering activity. Then, the network pharmacology was used to clarify the unique relationship between the Q-markers and their integral pharmacological action. Conclusion Combined with the results obtained, five active ingredients in the 50% ethanol extract fraction were given special considerations to be representative Q-markers: Alisol A, Alisol B, Alisol A 23-acetate, Alisol B 23-acetate and Alisol A 24-acetate, respectively. The chromatographic fingerprints based Q-marker was establishment. The integrated Q-marker screen may offer an alternative quality assessment of herbal medicines.
- Published
- 2018
15. The method of quality marker research and quality evaluation of traditional Chinese medicine based on drug properties and effect characteristics
- Author
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Hongbing Zhang, Gang Bai, Changxiao Liu, Jun Xu, Suxiao Gong, Tiejun Zhang, Yanqi Han, and Ya-zhuo Li
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Quality Control ,0301 basic medicine ,Traceability ,Computer science ,media_common.quotation_subject ,Pharmaceutical Science ,Traditional Chinese medicine ,01 natural sciences ,03 medical and health sciences ,Quality research ,Drug Discovery ,Humans ,Quality (business) ,Medicine, Chinese Traditional ,Research method ,media_common ,Chemical Ingredients ,Pharmacology ,Plants, Medicinal ,Quality assessment ,010401 analytical chemistry ,0104 chemical sciences ,030104 developmental biology ,Complementary and alternative medicine ,Risk analysis (engineering) ,Molecular Medicine ,Biomarkers ,Drugs, Chinese Herbal - Abstract
Background Quality of traditional Chinese medicine (TCM) plays a critical role in industry of TCM. Rapid development of TCM pharmaceutical areas is, however, greatly limited, since there are many issues not been resolved, concerning the quality study of TCM. Hypothesis/purpose Core concept of TCM quality as well as the characteristics of TCM was discussed, in order to guide the quality research and evaluation of TCM, further improve the level of TCM quality control. Study design/methods In this review, on the basis of systematic analysis of fundamental property and features of TCM in clinical application, the approaches and methods of quality marker (Q-marker) study were proposed through combination of transitivity and traceability of essentials of quality, correlation between chemical ingredients and drug property/efficacy, as well as analysis of endemicity of ingredients sharing similar pharmacophylogenetic and biosynthetic approaches. Results The approaches and methods of Q-marker study were proposed and the novel integrated pattern for quality assessment and control of TCM was established. Conclusion The core concept of Q-marker has helped to break through the bottleneck of the current fragmented quality research of TCM and improved the scientificity, integrity and systematicness of quality control.
- Published
- 2018
16. Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies
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Ying Xie, Hua Zhou, Liang Liu, Senling Feng, Ya-Zhuo Li, Zhong-Wen Yuan, Zhongqiu Liu, and Chang-Xiao Liu
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Male ,Biological Availability ,Pharmacology ,030226 pharmacology & pharmacy ,Madin Darby Canine Kidney Cells ,Rats, Sprague-Dawley ,03 medical and health sciences ,Tangeretin ,Dogs ,0302 clinical medicine ,Pharmacokinetics ,medicine ,Animals ,Humans ,Carbon Tetrachloride ,Chemistry ,Multidrug resistance-associated protein 2 ,Flavones ,Bioavailability ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Biochemistry ,Caco-2 ,Silybin ,030220 oncology & carcinogenesis ,Hepatocyte ,Paracellular transport ,ATP-Binding Cassette Transporters ,Efflux ,Caco-2 Cells ,Chemical and Drug Induced Liver Injury - Abstract
Biological responses of a variety of naturally occurring compounds in vivo were restrained by their poor oral bioavailability. Silybin, as one of the active ingredients of silymarin, has presented promising bioactivity for the treatment of chronic liver diseases and cancer. However, its exposure in body was limited. In this study, silybin was demonstrated to be substrates of both BCRP and MRP2 by utilizing monolayer Caco-2 cell model and confirmed in MDCK cells overexpressing specific efflux transporter. Of all compounds screened, tangeretin, a potent inhibitor of efflux transporters of BCRP, MRP2 and P-gp, was able to enhance exposure of silybin by inhibiting functions of the barriers mediating transcellular transport. Moreover, study carried out in sandwich-cultured rat hepatocyte (SCH) model showed that the biliary excretion index (BEI) and in vitro biliary clearance of silybin decreased as levels of tangeretin increased, indicating efflux transporters mediating biliary excretion of silybin might be involved. Pharmacokinetic behaviors of silybin in rats were altered by co-administration of tangeretin, in terms of increased AUC and Cmax of silybin by comparing with that of silybin given alone. In addition, results coming from CCl4-induced acute liver injury rat model revealed that protection effect of silybin against liver damage in the presence of tangeretin was significantly enhanced. All these data were evident that efflux transporters play a critical role in transcellular transport of silybin and account for its low bioavailability. Enhanced bioavailability of silybin with co-administration of tangeretin by significantly inhibiting the efflux transporters further boost its bioactivity which is of particular importance in clinical use.
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- 2018
17. Paleogeographic evolution of a Carboniferous–Permian sea in the southernmost part of the Central Asian Orogenic Belt, NW China: Evidence from microfacies, provenance and paleobiogeography
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Ya zhuo Niu, Jian qiang Wang, Guang Rong Shi, Kai Wang, Jian Ke Bai, Bo Yang, Jun lin Zhou, and Wen hua Ji
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Paleontology ,geography ,Provenance ,geography.geographical_feature_category ,Rift ,Permian ,Paleozoic ,Carboniferous ,Abyssal plain ,General Earth and Planetary Sciences ,Sedimentary rock ,Oceanic basin ,Geology - Abstract
The Paleo-Asian Ocean (PAO) has been regarded as a long-lived ocean from Neoproterozoic to early Mesozoic, and its subduction and closure built the Central Asian Orogenic Belt (CAOB), the largest accretionary orogenic belt in Earth's history. Although the tectonic evolution of the PAO has been discussed from diverse perspectives, the spatiotemporal dynamics in the evolution of the main branch of the PAO and its relationship with the Tethys remain contentious partly because of the absence of sedimentary evidence. Specifically, as far as the Beishan Orogenic Collage (BOC) in the southernmost part of CAOB is concerned, there remain at least two key questions: how did the BOC evolve tectonically and paleogeographically through the late Paleozoic; and which ophiolitic belt represented the main branch of the PAO in the BOC? This study recognized 27 volcano-sedimentary microfacies and 14 facies associations (FAs) in nine measured Carboniferous–Permian sections from the southern BOC. FA changes in the Visean–Capitanian megasequence indicate a Visean–Moscovian regressive sequence from fore-reef slopes to tidal flats and an Artinskian–Wordian transgressive sequence from fan-deltas to abyssal plains, separated by a continental and volcanic sequence straddling the Gzhelian–Sakmarian interval. Characteristics and lateral correlation of FAs suggest an epicontinental sea during Visean–Moscovian times, followed by a marine rift basin which eventually developed into a proto-oceanic basin during the Artinskian–Wordian. Paleobiogeographic evidence further suggests that this epicontinental sea was closely linked with the Tethyan oceans. Statistical comparisons of detrital zircon ages based on data compiled from previous and the present studies supports that this sea was mainly fed from Neoproterozoic and Ordovician–Silurian rocks (ca. 983 and 425 Ma) with a sparse influx of Mesoproterozoic and Paleoproterozoic detritus (ca. 2492, 1449, and 1302 Ma). During the Artinskian–Wordian, the rift basin was connected with the PAO based on the mixed cool- and warm-temperate marine faunas of the Boreal and Tethyan realms. This rift basin is thought to have been fed by two source-to-sink provenance systems, from either Ordovician–Silurian or Early Permian rocks (ca. 450 or 277 Ma), although provenance signatures were mixed because of turbidity and other currents in deep marine environments. We thus propose a succession of Carboniferous–Permian paleogeographic reconstruction maps for the BOC based on FA correlation and paleobiogeographic features. In these reconstruction models, the PAO is inferred to have been composed of a main branch (an oceanic basin) in the northern BOC as a part of the North Tianshan–Hongshishan–Solonker–Hegenshan Ocean and an epicontinental sea that subsequently evolved into a marine rift basin in the southern BOC.
- Published
- 2021
18. Integrating eggshell-derived CaCO3/MgO nanocomposites and chitosan into a biomimetic scaffold for bone regeneration
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Huang, Ya-zhuo, primary, Ji, Yong-rong, additional, Kang, Ze-wen, additional, Li, Fang, additional, Ge, Sheng-fang, additional, Yang, Da-Peng, additional, Ruan, Jing, additional, and Fan, Xian-qun, additional
- Published
- 2020
- Full Text
- View/download PDF
19. Nobiletin potentiates paclitaxel anticancer efficacy in A549/T xenograft model: Pharmacokinetic and pharmacological study
- Author
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Feng, Sen-Ling, primary, Tian, Yun, additional, Huo, Shuai, additional, Qu, Biao, additional, Liu, Rui-Ming, additional, Xu, Peng, additional, Li, Ya-Zhuo, additional, and Xie, Ying, additional
- Published
- 2020
- Full Text
- View/download PDF
20. Low temperature effects on carotenoids biosynthesis in the leaves of green and albino tea plant (Camellia sinensis (L.) O. Kuntze)
- Author
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Jing Zhuang, Ya-Zhuo Yang, Miao-Hua Han, Tong Li, and Rui-Min Teng
- Subjects
0106 biological sciences ,0301 basic medicine ,chemistry.chemical_classification ,Lutein ,biology ,Structural gene ,food and beverages ,Horticulture ,biology.organism_classification ,01 natural sciences ,03 medical and health sciences ,Pigment ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Biosynthesis ,visual_art ,visual_art.visual_art_medium ,Camellia sinensis ,Food science ,Cultivar ,Carotenoid ,Aroma ,010606 plant biology & botany - Abstract
Tea plant (Camellia sinensis (L.) O. Kuntze) is one of the most important economic crops worldwide, and it has a positive effect on human health. The low temperature in late autumn and early/late spring cold often cause damage to the normal physiological activities of tea plant, thereby reducing the quality and yield of tea. As one of the essential pigment of higher plant, carotenoids play an important role in the physiological activities of higher plant. In addition, as an important precursor of tea aroma volatiles, carotenoids are the important factors involved in the formation of tea quality. In this study, the main carotenoids, lutein and β-carotene, in leaves of common green tea cultivar 'Longjing 43′ and albino tea cultivar 'White leaf No.1′ were detected after low temperature treatment at 4 ℃. The results showed that the contents of lutein and β-carotene in 'Longjing 43′ were higher than that in 'White leaf No.1′, respectively. The chlorophyll content in two tea cultivars decreased and was significant positive correlation with two kinds of carotenoid content at low temperature. Under low temperature, the genes related to the biosynthesis pathway of methylerythritol 4-phosphate (MEP) and carotenoids all showed varying degrees of response with the changes of lutein and β-carotene content. The relative expression levels of CsDXS1, CsPSY1 and CsCHXB were up-regulated and higher than other related genes. Expression analysis of carotenoids biosynthesis genes and its correlation with carotenoids accumulation confirmed the regulatory role of structural genes in tea plant at low temperature. Promoter prediction results showed that the CsDXR, CsHDS1 and CsCHXB contain low-temperature response element LTR. This study provides reference for further study on the dynamic changes of carotenoids during the growth of tea plant.
- Published
- 2021
21. Interaction between Galectin-9/TIM-3 pathway and follicular helper CD4+ T cells contributes to viral persistence in chronic hepatitis C
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Ya Zhuo, Xin-Hong Wang, Lei Qin, A-Min Liu, Yan-Ping Wang, Hong-Jie Wu, and Yifu Zhang
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0301 basic medicine ,Pharmacology ,biology ,Hepatitis C virus ,BTLA ,General Medicine ,medicine.disease_cause ,CXCR5 ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Viral replication ,CTLA-4 ,Cell culture ,Immunology ,medicine ,biology.protein ,Antibody ,030215 immunology ,Galectin - Abstract
Both Galectin 9 (Gal-9)/T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) pathway and follicular helper CD4+ T (Tfh) cells play important roles in persistent hepatitis C virus (HCV) infection. Thus, we aimed to investigate the regulatory role of interaction between Gal-9/TIM-3 pathway and Tfh cells in chronic hepatitis C. A total of 44 chronic hepatitis C patients and 19 normal controls (NCs) were enrolled in this study. Purified CD4+ T cells were cultured by TIM-3 Fc protein, recombinant Gal-9, or IL-21 for 48h. TIM-3 expression, Tfh proportion, and IL-21 production was measured, respectively. The immunomodulatory role of Gal-9/TIM-3 and IL-21 was also investigated in HCV cell culture system in vitro. We found that the percentage corresponding to both TIM-3-positive and CXCR5+ICOS+ Tfh cells within CD4+ T cells, which correlated with HCV RNA replication, was significantly elevated in patients with chronic hepatitis C in comparison with those in NCs. Moreover, blockade of Gal-9/TIM-3 pathway by TIM-3 Fc protein increased Tfh cells proportion, IL-21 mRNA and protein expression within purified CD4+ T cells, while activation of Gal-9/TIM-3 signaling by Gal-9 stimulation decreased IL-21 production in both patients with chronic HCV infection and healthy individuals. Meanwhile, high concentrations (100 and 200ng/mL) of IL-21 stimulation also elevated TIM-3 expression on CD4+ T cells in chronic hepatitis C. Furthermore, TIM-3 blockage and IL-21 stimulation suppressed mRNA expressions of HCV-induced antiviral proteins (myxovirus resistance A and oligoadenylate synthetase) in Huh7.5 cells without affecting viral replication in HCV cell culture system. The interaction between Gal-9/TIM-3 pathway and Tfh cells contributed to viral persistent in chronic HCV infection, which might be pivotal for development of new therapeutic approaches for chronic hepatitis C.
- Published
- 2017
22. Inhibition of Cytochrome P450 by Nomilin and Obacunone and Potential Mechanism in Human Liver Microsomes
- Author
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Ya-zhuo Li, Gregory Ondieki, Xin He, Yun-long Chen, Junxiu Chen, Fang-Liang Zhang, and Yaowen Fan
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Pharmacology ,Human liver ,CYP3A4 ,biology ,Chemistry ,Cytochrome P450 ,030226 pharmacology & pharmacy ,01 natural sciences ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,03 medical and health sciences ,0302 clinical medicine ,Complementary and alternative medicine ,Biochemistry ,Ic50 values ,Microsome ,biology.protein ,Pharmacology (medical) ,Inhibitory effect ,Potential mechanism ,Incubation - Abstract
Objective Nomilin and obacunone are two important limonoids that are well known for their anticancer effect. Previous studies showed that limonoids had inhibitory effect on cytochrome P450 3A4 (CYP3A4). However these effects are inconclusive with regards to prediction of potential drug interactions. Methods Nomilin or obacunone was pre-incubated with HLMs for 30 min. Following 10-fold dilution from the pre-incubation concentration, a second incubation was performed in the presence of NADPH and cytochrome P450 substrates for 15 min. The reaction was quenched and the supernatants were analyzed by chromatography/mass spectrometry. Results In this study, nomilin and obacunone showed potent inhibitory effect on CYP3A4 with the IC50 values of 3.50 and 6.08 µmol/L, respectively. The inhibition of CYP3A4 was in a time-, concentration- and NADPH-dependent manner with Ki values of 2.92 and 1.25 µmol/L and Kinact values of 0.033 and 0.078 min−1 for nomilin and obacunone respectively. These results elucidated that they were time-dependent inhibitors for CYP3A4. Conclusion Concomitant use of limonoids and other drugs may call for extra caution for purposes of clinical safety.
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- 2017
23. Research and Application of Adlay in Medicinal Field
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Ya-zhuo Li, Jun Zhang, Zhen-ying Zhao, Fei Yu, and Changxiao Liu
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0301 basic medicine ,Pharmacology ,medicine.medical_specialty ,Traditional medicine ,business.industry ,Dietary supplement ,Alternative medicine ,Traditional Chinese medicine ,03 medical and health sciences ,Clinical therapy ,030104 developmental biology ,0302 clinical medicine ,Complementary and alternative medicine ,030220 oncology & carcinogenesis ,Chemical constituents ,Medicine ,Pharmacology (medical) ,Clinical efficacy ,business - Abstract
The traditional Chinese medicine (TCM) adlay has been used as a dietary supplement to promote health and treat various ailments for thousands of years. The effective and safe ingredients of TCM could be used as sources for developing new drugs. This paper reviews the main research and application of adlay seed in medicinal field in the following aspects: botanical resource, ethnopharmacological function, chemical constituents, pharmacology and pharmacokinetics, safety evaluation and toxicity, and clinical application. We hope that the review could help researchers mine the scientific values of adlay seed, innovative drug design, provide the guidance for the application in clinical therapy, and enhance the academic level and clinical efficacy of adlay seed.
- Published
- 2017
24. A New Concept on Quality Marker for Quality Assessment and Process Control of Chinese Medicines
- Author
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Yi-yu Cheng, De-an Guo, Wen-bin Hou, Tie-jun Zhang, Haiyu Xu, Changxiao Liu, Ya-zhuo Li, and Luqi Huang
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0301 basic medicine ,Pharmacology ,Traceability ,Traditional medicine ,Computer science ,Process (engineering) ,Quality assessment ,media_common.quotation_subject ,Environmental stress ,Product (business) ,03 medical and health sciences ,030104 developmental biology ,Complementary and alternative medicine ,Risk analysis (engineering) ,Process control ,Production (economics) ,Pharmacology (medical) ,Quality (business) ,media_common - Abstract
Chinese medicine (CM) is the most typical conventional therapy compared with any other traditional or alternative medicine systems. The active components of CMs are either primary or secondary metabolites generated by metabolic and biosynthetic enzymes in plants, protecting the plants from environmental stress. The characteristics of these metabolites are diverse, complicated and unique. In this paper, current approaches for quality assessment were extensively reviewed, a new concept of quality marker (Q-marker) was then proposed for CM quality assessment. Additionally, definition of the Q-marker, as well as the relevant methods, were discussed, on the basis of the biosynthetic pathways of secondary metabolites and source of biological active components. Study design of Q-marker is complex system for quality assessment and production process control of CM products with transitivity and traceability. Therefore, the system with characteristics of transmission and traceability is expected to be established for regulation of quality. Upon the concept which the transitivity and traceability in the quality assessment and production process control covered the entire process, such as raw materials, decoction slices, processing, extraction and production can be further enhanced. The transitivity and traceability will inevitably require close attention to “who, what, where, when, and why” details at each stage of Q-markers of CM production form raw materials to patent product. The establishing quality standards are enablers of many and various transitivity and traceability solutions, not a solution in them. It means that the transitivity and traceability system is readily link between products and across borders in quality. According to the thinking mode and methods of investigation on quality assessment of CM product, we focus on the entire process, in terms of safety and effectiveness and quality control. The standard preparation of CM or CM decoction is not only the basis for study of Q-marker, but also the basis for transmission and traceability of the quality of CM product.
- Published
- 2017
25. An Eight Amino Acid Segment Controls Oligomerization and Preferred Conformation of the two Non-visual Arrestins
- Author
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Ya Zhuo, Qiuyan Chen, Pankaj Sharma, Srinivas Chakravarthy, Susan M. Hanson, Tina M. Iverson, Vsevolod V. Gurevich, Sergey A. Vishnivetskiy, Derek J. Francis, Ivette Perez, Wayne L. Hubbell, Sandra Berndt, Candice S. Klug, Evan K. Brooks, Christian Altenbach, and Xuanzhi Zhan
- Subjects
Models, Molecular ,Gene isoform ,Phytic Acid ,genetic structures ,Arrestins ,Protein Conformation ,G protein ,Oligomer ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Structural Biology ,Humans ,Protein Isoforms ,Amino Acids ,Receptor ,Molecular Biology ,030304 developmental biology ,G protein-coupled receptor ,chemistry.chemical_classification ,0303 health sciences ,Binding Sites ,Chemistry ,Spectrum Analysis ,eye diseases ,Amino acid ,Solutions ,Knockout mouse ,Biophysics ,sense organs ,Protein Multimerization ,030217 neurology & neurosurgery ,Function (biology) ,Protein Binding - Abstract
G protein coupled receptors signal through G proteins or arrestins. A long-standing mystery in the field is why vertebrates have two non-visual arrestins, arrestin-2 and arrestin-3. These isoforms are ~75% identical and 85% similar; each binds numerous receptors, and appear to have many redundant functions, as demonstrated by studies of knockout mice. We previously showed that arrestin-3 can be activated by inositol-hexakisphosphate (IP6). IP6 interacts with the receptor-binding surface of arrestin-3, induces arrestin-3 oligomerization, and this oligomer stabilizes the active conformation of arrestin-3. Here, we compared the impact of IP6 on oligomerization and conformational equilibrium of the highly homologous arrestin-2 and arrestin-3 and found that these two isoforms are regulated differently. In the presence of IP6, arrestin-2 forms "infinite" chains, where each promoter remains in the basal conformation. In contrast, full length and truncated arrestin-3 form trimers and higher-order oligomers in the presence of IP6; we showed previously that trimeric state induces arrestin-3 activation (Chen et al., 2017). Thus, in response to IP6, the two non-visual arrestins oligomerize in different ways in distinct conformations. We identified an insertion of eight residues that is conserved across arrestin-2 homologs, but absent in arrestin-3 that likely accounts for the differences in the IP6 effect. Because IP6 is ubiquitously present in cells, this suggests physiological consequences, including differences in arrestin-2/3 trafficking and JNK3 activation. The functional differences between two non-visual arrestins are in part determined by distinct modes of their oligomerization. The mode of oligomerization might regulate the function of other signaling proteins.
- Published
- 2021
26. Rapid Analysis and Identification of Absorbed Components and Their Metabolites of Yuanhu Zhitong Dropping Pill in Rat Plasma and Brain Tissue Using UPLC-Q-TOF/MS with Multivariate Statistical Analysis
- Author
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Tie-jun Zhang, Hongbing Zhang, Jun Xu, Changxiao Liu, Xi-min Zhang, and Ya-zhuo Li
- Subjects
Pharmacology ,Chromatography ,Chemistry ,Yuanhu zhitong ,010401 analytical chemistry ,Analytical chemistry ,Brain tissue ,Rat brain ,030226 pharmacology & pharmacy ,01 natural sciences ,Uplc q tof ms ,0104 chemical sciences ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Complementary and alternative medicine ,Pharmacology (medical) ,Multivariate statistical ,Xenobiotic - Abstract
Objective To establish an effective approach for rapid and comprehensive analysis on the absorbed and metabolic components in rats after ig administration of Yuanhu Zhitong Dropping Pill (YHZT). Methods Based on the combination of UPLC-Q-TOF/MS and multivariate statistical analysis, the absorbed prototype constituents and their metabolites in rat plasma were rapidly analyzed and identified, and the components absorbed into brain were further identified by comparing the extracted ion chromatograms (EICs) of control and brain tissue samples of dosed rats. Results A total of 38 YHZT-related xenobiotic compounds were detected and identified as the potential bioactive constituents in rat plasma, including 24 absorbed prototype constituents and 14 metabolites. In particular, of all prototype constituents, 14 were also detected in rat brain tissue, indicating that they could penetrate the blood-brain barrier and enter into brain. Conclusion An effective method is established and applied to analyze the potential bioactive constituents in YHZT, which provides a pathway to further investigate the pharmacological pattern and mechanism of YHZT.
- Published
- 2016
27. Molecular Simulation Study on Bentysrepinine Metabolites Improving Binding Affinity of HBV DNA Polymerase
- Author
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Changxiao Liu, Shiqi Dong, Min Gong, Ya-zhuo Li, Guangyi Liang, Yu-li Wang, Fan-cui Meng, and Huirong Fan
- Subjects
0301 basic medicine ,Pharmacology ,Hepatitis B virus ,biology ,Traditional medicine ,DNA polymerase ,business.industry ,Molecular simulation ,medicine.disease_cause ,Bentysrepinine ,Hbv dna polymerase ,Hydrophobic effect ,03 medical and health sciences ,030104 developmental biology ,Complementary and alternative medicine ,Biochemistry ,Docking (molecular) ,biology.protein ,medicine ,Pharmacology (medical) ,business ,Polymerase - Abstract
Objective To study the effect of bentysrepinine (Y101) metabolites on improving binding affinity of HBV DNA polymerase. Methods The binding mode of Y101 and its metabolites with DNA polymerase has been driven by hydrophobic interaction. Results Two compounds, T2 and T4, exhibited the improvement of the binding affinity to HBV DNA polymerase protein, which suggests that the inhibitory activity against HBV DNA polymerase protein can be enhanced. Conclusion The variant docking poses of T2 and T4 might imply the novel recognition of inhibitory effects of T2 and T4, in comparison with Y101.
- Published
- 2016
28. Prediction of quality markers of traditional Chinese medicines based on network pharmacology
- Author
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Wang, Yu-li, primary, Cui, Tao, additional, Li, Ya-zhuo, additional, Liao, Mao-liang, additional, Zhang, Hong-bing, additional, Hou, Wen-bin, additional, Zhang, Tie-jun, additional, Liu, Liang, additional, Huang, He, additional, and Liu, Chang-xiao, additional
- Published
- 2019
- Full Text
- View/download PDF
29. Network toxicology and LC-MS-based metabolomics: New approaches for mechanism of action of toxic components in traditional Chinese medicines
- Author
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Li, Xin-yu, primary, Jin, Xin, additional, Li, Ya-zhuo, additional, Gao, Dan-dan, additional, Liu, Rui, additional, and Liu, Chang-xiao, additional
- Published
- 2019
- Full Text
- View/download PDF
30. Development and Application of Network Toxicology in Safety Research of Chinese Materia Medica
- Author
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Rui Liu, Ya-zhuo Li, Jing-wen Qi, Xuefeng Xiao, Hui-rong Fan, Jie Wang, Zong-peng Zhang, Xiu-ping Shen, Changxiao Liu, and Xing Zhang
- Subjects
Pharmacology ,Toxicology ,Complementary and alternative medicine ,Scientific development ,business.industry ,Network pharmacology ,Materia medica ,Medicine ,Pharmacology (medical) ,business ,Biological network - Abstract
Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, particularly investigate the toxic effects of drugs and/or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica (CMM). The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development of the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced.
- Published
- 2015
31. In Silico Molecular Docking Study of Repensine and Bentysrepinine against HBV DNA Polymerase
- Author
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Fan-cui Meng, Wei-ren Xu, Zhengming Huang, Guangyi Liang, Ya-zhuo Li, and Changxiao Liu
- Subjects
Pharmacology ,Hepatitis B virus ,biology ,DNA polymerase ,In silico ,virus diseases ,cccDNA ,medicine.disease_cause ,Molecular biology ,In vitro ,Reverse transcriptase ,Complementary and alternative medicine ,Docking (molecular) ,biology.protein ,medicine ,Pharmacology (medical) ,Polymerase - Abstract
Bentysrepinine (Y101), a derivative of repensine, is a novel di-peptide structure isolated from Dichondra repens. In vitro and in vivo tests exhibited that bentysrepinine markedly inhibited DNA-HBV and cccDNA activities. The binding mode of Y101 and repensine with DNA polymerase was driven by hydrophobic interactions. This might provide novel recognition of inhibitory effect of Y101 against HBV, though its inhibition mechanism needs to be validated by bio-assay at cellular level and of polymerase activity. Preliminary docking study suggested that Y101 might be able to inhibit HIV inverse transcriptase, also have the potential to interact with DNA polymerase and HCV NS5B polymerase.
- Published
- 2015
32. Endoscopic approach to the trigeminal nerve: An anatomic study
- Author
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Ming Song, Jia-ping Zheng, Ya-zhuo Zhang, Li Chuzhong, Xuyi Zong, and Xiang-xin Zhan
- Subjects
Adult ,Natural Orifice Endoscopic Surgery ,Sphenoid Sinus ,Mandibular Nerve ,Pterygopalatine Fossa ,Mandibular nerve ,Ophthalmic Nerve ,medicine.artery ,Cadaver ,Maxilla ,Maxillary Nerve ,Photography ,medicine ,Humans ,Trigeminal Nerve ,Pterygopalatine fossa ,Endoscopes ,Trigeminal nerve ,business.industry ,Maxillary nerve ,Temporal Bone ,Anatomy ,Cochlea ,Ganglion ,medicine.anatomical_structure ,Trigeminal Ganglion ,Otorhinolaryngology ,Surgery ,Pterygopalatine ganglion ,Nasal Cavity ,Oral Surgery ,Internal carotid artery ,Cadaveric spasm ,business ,Carotid Artery, Internal ,Petrous Bone - Abstract
Objective To describe an endoscopic perspective of the surgical anatomy of the trigeminal nerve. Methods Nine adult cadaveric heads were dissected endoscopically. Results Opening the pterygopalatine fossa is important because many key anatomical structures (V2, pterygopalatine ganglion, vidian nerve) can be identified and traced to other areas of the trigeminal nerve. From the pterygopalatine ganglion, the maxillary nerve and vidian nerve can be identified, and they can be traced to the gasserian ganglion and internal carotid artery. An anteromedial maxillectomy increases the angle of approach from the contralateral nares due to an increase in diameter of the piriform aperture, and provides excellent access to the mandibular nerve, the petrous carotid, and the cochlea. Conclusions Identification of key anatomical structures in the pterygopalatine fossa can be used to identify other areas of the trigeminal nerve, and an anteromedial maxillectomy is necessary to expose the ipsilateral mandibular nerve and contralateral cranial level of the trigeminal nerve.
- Published
- 2014
33. Identification of Receptor Binding-induced Conformational Changes in Non-visual Arrestins
- Author
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Ya Zhuo, Xuanzhi Zhan, Vsevolod V. Gurevich, Sergey A. Vishnivetskiy, and Candice S. Klug
- Subjects
Rhodopsin ,genetic structures ,Arrestins ,Biochemistry ,Protein Structure, Secondary ,Heterotrimeric G protein ,Arrestin ,Humans ,Receptor ,Molecular Biology ,G protein-coupled receptor ,biology ,Cell Biology ,eye diseases ,Protein Structure, Tertiary ,Cell biology ,Cytosol ,biology.protein ,Phosphorylation ,Spin Labels ,sense organs ,Signal transduction ,hormones, hormone substitutes, and hormone antagonists ,Molecular Biophysics ,Signal Transduction - Abstract
The non-visual arrestins, arrestin-2 and arrestin-3, belong to a small family of multifunctional cytosolic proteins. Non-visual arrestins interact with hundreds of G protein-coupled receptors (GPCRs) and regulate GPCR desensitization by binding active phosphorylated GPCRs and uncoupling them from heterotrimeric G proteins. Recently, non-visual arrestins have been shown to mediate G protein-independent signaling by serving as adaptors and scaffolds that assemble multiprotein complexes. By recruiting various partners, including trafficking and signaling proteins, directly to GPCRs, non-visual arrestins connect activated receptors to diverse signaling pathways. To investigate arrestin-mediated signaling, a structural understanding of arrestin activation and interaction with GPCRs is essential. Here we identified global and local conformational changes in the non-visual arrestins upon binding to the model GPCR rhodopsin. To detect conformational changes, pairs of spin labels were introduced into arrestin-2 and arrestin-3, and the interspin distances in the absence and presence of the receptor were measured by double electron electron resonance spectroscopy. Our data indicate that both non-visual arrestins undergo several conformational changes similar to arrestin-1, including the finger loop moving toward the predicted location of the receptor in the complex as well as the C-tail release upon receptor binding. The arrestin-2 results also suggest that there is no clam shell-like closure of the N- and C-domains and that the loop containing residue 136 (homolog of 139 in arrestin-1) has high flexibility in both free and receptor-bound states.
- Published
- 2014
34. Band gaps of Lamb waves propagating in one-dimensional periodic and nesting Fibonacci superlattices thin plates
- Author
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Ya-Zhuo Xie, Min Zhao, Xing-Gan Zhang, and Jian Gao
- Subjects
Physics ,Fibonacci number ,Condensed matter physics ,Plane wave expansion method ,Band gap ,Superlattice ,Metals and Alloys ,Bragg's law ,Surfaces and Interfaces ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Lamb waves ,Materials Chemistry ,Nesting (computing) ,Dispersion (water waves) - Abstract
We study the band-gap structures of Lamb waves propagating in one-dimensional periodic sequences thin plate and nesting Fibonacci superlattices thin plates with different generation numbers. The dispersion curves are calculated based on the plane wave expansion method. It is found that more band gaps occur in nesting Fibonacci superlattices than in periodic phononic crystals. This is because the cells in nesting Fibonacci superlattices are quasi-periodic sequences at micro-scale, which can cause splitting of band gaps. Additionally, the periodic feature of nesting Fibonacci superlattices at macro-scale enhances Bragg scattering, which causes band gaps to become flat. As the growth of generation numbers, the characteristic of curves becomes flatter. Compared with the periodic model, the special structures of nesting Fibonacci superlattices can be used to adjust the width of band gaps and the frequency ranges of phononic crystals.
- Published
- 2013
35. The Effects of Smad3 on Adrenocorticotropic Hormone–Secreting Pituitary Adenoma Development, Cell Proliferation, Apoptosis, and Hormone Secretion
- Author
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Zhou, Yong-Zhi, primary, Li, Chu-Zhong, additional, Gao, Hua, additional, and Zhang, Ya-Zhuo, additional
- Published
- 2018
- Full Text
- View/download PDF
36. Three-Dimensional Printed Skull Base Simulation for Transnasal Endoscopic Surgical Training
- Author
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Zheng, Jia-Ping, primary, Li, Chu-Zhong, additional, Chen, Guo-Qiang, additional, Song, Gui-Dong, additional, and Zhang, Ya-Zhuo, additional
- Published
- 2018
- Full Text
- View/download PDF
37. Role of tangeretin as a potential bioavailability enhancer for silybin: Pharmacokinetic and pharmacological studies
- Author
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Yuan, Zhong-Wen, primary, Li, Ya-Zhuo, additional, Liu, Zhong-Qiu, additional, Feng, Sen-ling, additional, Zhou, Hua, additional, Liu, Chang-Xiao, additional, Liu, Liang, additional, and Xie, Ying, additional
- Published
- 2018
- Full Text
- View/download PDF
38. Emerging Role of α2,6-Sialic Acid as a Negative Regulator of Galectin Binding and Function
- Author
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Ya Zhuo and Susan L. Bellis
- Subjects
Glycan ,animal structures ,Glycosylation ,Galectins ,Cell ,Oligosaccharides ,Plasma protein binding ,Biology ,Biochemistry ,chemistry.chemical_compound ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Molecular Biology ,Galectin ,Lectin ,Minireviews ,Galactosides ,Cell Biology ,Sialic acid ,Cell biology ,stomatognathic diseases ,medicine.anatomical_structure ,chemistry ,Sialic Acids ,biology.protein ,Function (biology) ,Protein Binding - Abstract
Galectins are β-galactoside-binding lectins that regulate diverse cell behaviors, including adhesion, migration, proliferation, and apoptosis. Galectins can be expressed both intracellularly and extracellularly, and extracellular galectins mediate their effects by associating with cell-surface oligosaccharides. Despite intensive current interest in galectins, strikingly few studies have focused on a key enzyme that acts to inhibit galectin signaling, namely β-galactoside α2,6-sialyltransferase (ST6Gal-I). ST6Gal-I adds an α2,6-linked sialic acid to the terminal galactose of N-linked glycans, and this modification blocks galectin binding to β-galactosides. This minireview summarizes the evidence suggesting that ST6Gal-I activity serves as an "off switch" for galectin function.
- Published
- 2011
39. Tumor cell migration and invasion are regulated by expression of variant integrin glycoforms
- Author
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Kristin M. Hennessy, Ya Zhuo, Eric C. Seales, Susan L. Bellis, William C. Clem, and Faheem M. Shaikh
- Subjects
Integrins ,Integrin ,Cell ,Neuraminidase ,Adenocarcinoma ,Collagen Type I ,Article ,Small hairpin RNA ,Mice ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,Cell Adhesion ,medicine ,Animals ,Humans ,Protein Isoforms ,Neoplasm Invasiveness ,Cell adhesion ,beta-D-Galactoside alpha 2-6-Sialyltransferase ,Matrigel ,biology ,Cell migration ,Cell Biology ,Molecular biology ,Sialyltransferases ,Cell biology ,medicine.anatomical_structure ,Cell culture ,Colonic Neoplasms ,Sialic Acids ,ras Proteins ,biology.protein - Abstract
The ST6Gal-I glycosyltransferase, which adds alpha2-6-linked sialic acids to glycoproteins, is overexpressed in colon adenocarcinoma, and enzyme activity is correlated with tumor cell invasiveness. Previously we reported that forced expression of oncogenic ras in HD3 colonocytes causes upregulation of ST6Gal-I, leading to increased alpha2-6 sialylation of beta1 integrins. To determine whether ras-induced sialylation is involved in promoting the tumor cell phenotype, we used shRNA to downregulate ST6Gal-I in ras-expressors, and then monitored integrin-dependent responses. Here we show that forced ST6Gal-I downregulation, leading to diminished alpha2-6 sialylation of integrins, inhibits cell adhesion to collagen I, a beta1 ligand. Correspondingly, collagen binding is reduced by enzymatic removal of cell surface sialic acids from ras-expressors with high ST6Gal-I levels (i.e., no shRNA). Cells with forced ST6Gal-I downregulation also exhibit decreased migration on collagen I and diminished invasion through Matrigel. Importantly, GD25 cells, which lack beta1 integrins (and ST6Gal-I), do not demonstrate differential invasiveness when forced to express ST6Gal-I, suggesting that the effects of variant sialylation are mediated specifically by beta1 integrins. The observation that cell migration and invasion can be blocked in oncogenic ras-expressing cells by forcing ST6Gal-I downregulation implicates differential sialylation as an important ras effector, and also suggests that ST6Gal-I is a promising therapeutic target.
- Published
- 2008
40. Proteolytic Shedding of ST6Gal-I by BACE1 Regulates the Glycosylation and Function of α4β1 Integrins
- Author
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John K. Wakefield, Ya Zhuo, Alexis McBrayer, Susan L. Bellis, and Alencia V. Woodard-Grice
- Subjects
MAPK/ERK pathway ,Glycosylation ,Sialyltransferase ,Cellular differentiation ,CD14 ,Integrin ,Lipopolysaccharide Receptors ,Down-Regulation ,Vascular Cell Adhesion Molecule-1 ,Glycobiology and Extracellular Matrices ,Integrin alpha4beta1 ,Biology ,Biochemistry ,Monocytes ,Antigens, CD ,Aspartic Acid Endopeptidases ,Humans ,Molecular Biology ,Protein kinase C ,U937 cell ,Macrophages ,Cell Differentiation ,U937 Cells ,Cell Biology ,Molecular biology ,Sialyltransferases ,Up-Regulation ,Protein Subunits ,Sialic Acids ,biology.protein ,Amyloid Precursor Protein Secretases ,Amyloid precursor protein secretase ,Protein Modification, Translational - Abstract
Differentiation of monocytes into macrophages is accompanied by increased cell adhesiveness, due in part to the activation of alpha4beta1 integrins. Here we report that the sustained alpha4beta1 activation associated with macrophage differentiation results from expression of beta1 integrin subunits that lack alpha2-6-linked sialic acids, a carbohydrate modification added by the ST6Gal-I sialyltransferase. During differentiation of U937 monocytic cells and primary human CD14(+) monocytes, ST6Gal-I is down-regulated, leading to beta1 hyposialylation and enhanced alpha4beta1-dependent VCAM-1 binding. Importantly, ST6Gal-I down-regulation results from cleavage by the BACE1 secretase, which we show is dramatically up-regulated during macrophage differentiation. BACE1 up-regulation, ST6Gal-I shedding, beta1 hyposialylation, and alpha4beta1-dependent VCAM-1 binding are all temporally correlated and share the same signaling mechanism (protein kinase C/Ras/ERK). Preventing ST6Gal-I down-regulation (and therefore integrin hyposialylation), through BACE1 inhibition or ST6Gal-I constitutive overexpression, eliminates VCAM-1 binding. Similarly, preventing integrin hyposialylation inhibits a differentiation-induced increase in the expression of an activation-dependent conformational epitope on the beta1 subunit. Collectively, these results describe a novel mechanism for alpha4beta1 regulation and further suggest an unanticipated role for BACE1 in macrophage function.
- Published
- 2008
41. Sialylation of β1 Integrins Blocks Cell Adhesion to Galectin-3 and Protects Cells against Galectin-3-induced Apoptosis
- Author
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Ya Zhuo, Roger Chammas, and Susan L. Bellis
- Subjects
Cell Biology ,Molecular Biology ,Biochemistry - Published
- 2008
42. Inhibition of Cytochrome P450 by Nomilin and Obacunone and Potential Mechanism in Human Liver Microsomes
- Author
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Fan, Yao-wen, primary, Chen, Yun-long, additional, Chen, Jun-xiu, additional, Zhang, Fang-liang, additional, Ondieki, Gregory, additional, Li, Ya-zhuo, additional, and He, Xin, additional
- Published
- 2017
- Full Text
- View/download PDF
43. A novel efficient medium for chromogenic catalysis of tetramethylbenzidine with horseradish peroxidase
- Author
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Li, Meng, primary, Huang, Xiang-Rong, additional, Guo, Yi, additional, Shang, Ya-Zhuo, additional, and Liu, Hong-Lai, additional
- Published
- 2017
- Full Text
- View/download PDF
44. A Novel Invasive-Related Biomarker in Three Subtypes of Nonfunctioning Pituitary Adenomas
- Author
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Chen, Yong, primary, Chuan, Hong-Li, additional, Yu, Sheng-Yuan, additional, Li, Chu-Zhong, additional, Wu, Zhe-Bao, additional, Li, Gui-Lin, additional, and Zhang, Ya-Zhuo, additional
- Published
- 2017
- Full Text
- View/download PDF
45. A New Concept on Quality Marker for Quality Assessment and Process Control of Chinese Medicines
- Author
-
Liu, Chang-xiao, primary, Cheng, Yi-yu, additional, Guo, De-an, additional, Zhang, Tie-jun, additional, Li, Ya-zhuo, additional, Hou, Wen-bin, additional, Huang, Lu-qi, additional, and Xu, Hai-yu, additional
- Published
- 2017
- Full Text
- View/download PDF
46. Synthesis of diethers derived from furoin by phase transfer catalysis under microwave irradiation
- Author
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Ya Zhuo Li, Feng Zhang, Ji Kui Sun, Da Wei Gao, and Yu Min Zhang
- Subjects
chemistry.chemical_classification ,Furoin ,chemistry.chemical_compound ,chemistry ,Phase (matter) ,Microwave irradiation ,Organic chemistry ,Halide ,General Chemistry ,Alkylation ,Photochemistry ,Alkyl ,Catalysis - Abstract
A series of new diethers were obtained by alkylation of furoin under microwave irradiation (MWI) in phase transfer catalysis (PTC) conditions. The products of alkyl halides were synthesized in good yields (>75%) within a few minutes, and the products of dihalides were synthesized in fair yields (about 45%). The yields are dramatically improved compared to conventional heating under the same conditions, in spite of similar profiles of rising in temperature.
- Published
- 2007
47. RF power and I/Q imbalance calibration in B3G/4G MIMO-OFDM systems
- Author
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Mingyu Zhou, Ping Zhang, and Ya-zhuo Li
- Subjects
Computer Networks and Communications ,Computer science ,business.industry ,ComputerSystemsOrganization_COMPUTER-COMMUNICATIONNETWORKS ,RF power amplifier ,Transmitter ,MIMO ,Data_CODINGANDINFORMATIONTHEORY ,MIMO-OFDM ,Interference (wave propagation) ,Frequency-division multiplexing ,Signal Processing ,Electronic engineering ,Bit error rate ,Radio frequency ,Telecommunications ,business ,Computer Science::Information Theory ,Information Systems - Abstract
Radio frequency (RF) front-end nonidealities in multi-input and multi-output (MIMO) systems are more serious than in single-input and single-output systems and must be calibrated. According to the effects of RF power and in-phase/quadrature-phase (I/Q) imbalance, calibration methods for multi-input and multi-output-orthogonal frequency division multiplexing (MIMC-OFDM) systems in transmitter and interference in receiver are improved, respectively, in this article. Furthermore, a calibration scheme including I/Q imbalance errors and amplitude variations is proposed and implemented in the B3G/4G time division duplex communication system. Simulation results show that the calibration algorithms are feasible, and the bit error rate (BER) performances for MIMO-OFDM systems are improved after calibrations.
- Published
- 2007
48. Integrative proteomics and transcriptomics revealed that activation of the IL-6R/JAK2/STAT3/MMP9 signaling pathway is correlated with invasion of pituitary null cell adenomas
- Author
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Feng, Jie, primary, Yu, Sheng-Yuan, additional, Li, Chu-Zhong, additional, Li, Zhen-Ye, additional, and Zhang, Ya-Zhuo, additional
- Published
- 2016
- Full Text
- View/download PDF
49. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis
- Author
-
Ya Zhuo, Maureen Pickarski, Gideon A. Rodan, Le T. Duong, Gregg Wesolowski, and Tadashi Hayami
- Subjects
Male ,Cartilage, Articular ,Pathology ,medicine.medical_specialty ,Time Factors ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Anterior cruciate ligament ,Osteoarthritis ,Menisci, Tibial ,Bone and Bones ,Chondrocyte ,Bone remodeling ,Rats, Sprague-Dawley ,Spinal Osteophytosis ,Chondrocytes ,medicine ,Animals ,Femur ,Anterior Cruciate Ligament ,Tibia ,business.industry ,Cartilage ,Calcinosis ,Anatomy ,Articular cartilage damage ,medicine.disease ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Eburnation ,Disease Progression ,Joints ,Bone Remodeling ,business - Abstract
Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction, subchondral bone sclerosis, and osteophyte formation. Subchondral bone stiffness has been proposed to initiate and/or contribute to cartilage deterioration in OA. The purpose of this study was to characterize subchondral bone remodeling, cartilage damage, and osteophytosis during the disease progression in two models of surgically induced OA. Rat knee joints were subjected either to anterior cruciate ligament transection (ACLT) alone or in combination with resection of medial menisci (ACLT + MMx). Histopathological changes in the surgical joints were compared with sham at 1, 2, 4, 6, and 10 weeks post-surgery. Using a modified Mankin scoring system, we demonstrate that articular cartilage damage occurs within 2 weeks post-surgery in both surgical models. Detectable cartilage surface damage and proteoglycan loss were observed as early as 1 week post-surgery. These were followed by the increases in vascular invasion into cartilage, in loss of chondrocyte number and in cell clustering. Histomorphometric analysis revealed subchondral bone loss in both models within 2 weeks post-surgery followed by significant increases in subchondral bone volume relative to sham up to 10 weeks post-surgery. Incidence of osteophyte formation was optimally observed in ACLT joints at 10 weeks and in ACLT + MMx joints at 6 weeks post-surgery. In summary, the two surgically induced rat OA models share many characteristics seen in human and other animal models of OA, including progressive articular cartilage degradation, subchondral bone sclerosis, and osteophyte formation. Moreover, increased subchondral bone resorption is associated with early development of cartilage lesions, which precedes significant cartilage thinning and subchondral bone sclerosis. Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone resorption inhibitors as potential disease-modifying pharmaco-therapies.
- Published
- 2006
50. M-CSF induces the stable interaction of cFms with αVβ3 integrin in osteoclasts
- Author
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Gideon A. Rodan, Gregg Wesolowski, Le T. Duong, Ya Zhuo, John A. Hamilton, and Caryn L. Elsegood
- Subjects
Macrophage colony-stimulating factor ,Podosome ,Integrin ,Osteoclasts ,Receptor, Macrophage Colony-Stimulating Factor ,Biology ,Biochemistry ,Mice ,chemistry.chemical_compound ,Animals ,Immunoprecipitation ,Proto-Oncogene Proteins c-cbl ,Phosphorylation ,Kinase activity ,Cells, Cultured ,Integrin alphaVbeta3 ,Macrophage Colony-Stimulating Factor ,Receptor Protein-Tyrosine Kinases ,Tyrosine phosphorylation ,Cell Biology ,Cell biology ,Crk-Associated Substrate Protein ,chemistry ,biology.protein ,Signal transduction ,Signal Transduction - Abstract
The macrophage colony stimulating factor receptor (cFms) and alpha(V)beta(3) integrin are both abundantly expressed and play critical roles in the differentiation, survival and migration of osteoclasts. We have previously demonstrated that cross-talk between cFms- and alpha(V)beta(3)-mediated signaling pathways regulated the cytoskeletal organization required for osteoclast migration. To investigate the nature of interaction between the two receptors, we sequentially used anion-exchange chromatography and immunoprecipitation to purify alpha(V)beta(3)-associated protein complexes. We have demonstrated that cFms stably associated with alpha(V)beta(3) in osteoclasts during adhesion, and that the association was induced by macrophage colony stimulating factor (M-CSF) stimulation. However, the kinetics of association of alpha(V)beta(3) and cFms did not correlate with the kinetics of tyrosine phosphorylation of cFms. Instead, maximally observed alpha(V)beta(3)/cFms association was after the peak of cFms tyrosine phosphorylation and correlated inversely with the total amount of cFms remaining. Furthermore, the complex containing cFms and alpha(V)beta(3) also contained a number of other signaling molecules including Pyk2, p130(Cas) and c-Cbl, known downstream regulators of the integrin-mediated signaling pathways in osteoclasts. In the presence of M-CSF, co-localization of alpha(V)beta(3) integrin and cFms was identified in the podosomal actin ring of the osteoclast during adhesion on glass. Interestingly, co-localization of both receptors was not found in the sealing zone, but in punctate structures associated with adhesion- or transcytosis-like structures in osteoclasts on bone. Taken together, we suggest that the association of alpha(V)beta(3) and cFms could be the result of signaling following tyrosine phosphorylation of cFms. The recruitment of cFms to alpha(V)beta(3) integrin may be an integral part of a larger signaling complex via which both of adhesion- and growth factor receptors coordinately regulate osteoclast adhesion, motility and membrane trafficking.
- Published
- 2006
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