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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Comparison of the Full-Length and 152~528 Truncate of Human Cyclic Nucleotide Phosphodiesterase 4B2 for the Characterization of Inhibitors

Author(s): Xiang Zhang, Shu He, Xiaolei Hu, Jing Wu, Xinpeng Li, Fei Liao* and Xiaolan Yang*

Volume 22, Issue 1, 2019

Page: [49 - 58] Pages: 10

DOI: 10.2174/1386207322666190306142810

Price: $65

Abstract

Aim and Objective: Human full-length cyclic nucleotide phosphodiesterase isozyme 4B2 (hPDE4B2) as the target for screening and characterizing inhibitors suffers from low activity yield and the coexistence of two conformational states bearing different affinities for (R)-rolipram. Hence, the 152~528 truncate of hPDE4B2 existing only in the low-affinity conformation state for (R)-rolipram was compared against the full-length hPDE4B2 to characterize inhibitors.

Materials and Methods: With 6His-SUMO tag at the N-terminus, both the full-length hPDE 4B2 (SF-hPDE4B2) and the 152~528 truncate (ST-hPDE4B2) were expressed in Escherichia coli cells, purified through Ni-NTA column and compared for the characterization of inhibitors. The inhibition constants (Ki) of some synthesized rolipram analogues against both targets were determined with 96-well microplate through the coupled action of monophosphatase on AMP and spectrophotometric assay of phosphate with malachite green.

Results: After affinity purification with Ni2+-NTA column, ST-hPDE4B2 showed about 30-fold higher specific activity and 100-fold higher activity yield than SF-hPDE4B2; Ki of (R)-rolipram on ST-hPDE4B2 was consistent with that on the low-affinity state of the untagged full-length hPDE4B2 expressed in insect cells. Of some representative rolipram analogues as inhibitors, a dual-logarithm model quantitatively described their monotonic association, and Ki from 0.010 mM to 8.5 mM against SF-hPDE4B2 was predicted from Ki against ST-hPDE4B2, supporting the discovery of consistent hits by the use of both targets with a pair of properly-set cutoffs.

Conclusion: ST-hPDE4B2 with much higher activity yield may be a favorable alternative target to characterize/screen rolipram analogues as hPDE4B inhibitors in high-throughput mode.

Keywords: Human cyclic nucleotide phosphodiesterase 4B, truncate, inhibitor, rolipram, SUMO tag, inflammatory.

[1]
Houslay, M.D.; Schafer, P.; Zhang, K.Y. Keynote review: Phosphodiesterase-4 as a therapeutic target. Drug Discov. Today, 2005, 10(22), 1503-1519.
[2]
Lipworth, B.J. Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet, 2005, 36(9454), 167-175.
[3]
Page, C.P.; Spina, D. Selective PDE inhibitors as novel treatments for respiratory diseases. Curr. Opin. Pharmacol., 2012, 12(3), 275-286.
[4]
Bora, R.S.; Malik, R.; Arya, R.; Gupta, D.; Singh, V.; Aggarwal, N.; Dastidar, S.; Ray, A.; Saini, K.S. A reporter gene assay for screening of PDE4 subtype selective inhibitors. Biochem. Biophys. Res. Commun., 2007, 356(1), 153-158.
[5]
Wunder, F.; Quednau, R.; Geerts, A.; Barg, M.; Tersteegen, A. Characterization of the cellular activity of PDE 4 inhibitors using two novel PDE 4 reporter cell lines. Mol. Pharm., 2013, 10(10), 3697-3705.
[6]
Bardelle, C.; Smales, C.; Ito, M.; Nomoto, K.; Wong, E.Y.; Kato, H.; Saeki, T.; Staddon, J.M. Phosphodiesterase 4 conformers: Preparation of recombinant enzymes and assay for inhibitors. Anal. Biochem., 1999, 275(2), 148-155.
[7]
Kariv, I.I.; Stevens, M.E.; Behrens, D.L.; Oldenburg, K.R. High throughput quantitation of cAMP production mediated by activation of seven transmembrane domain receptors. J. Biomol. Screen., 1999, 4(1), 27-32.
[8]
Li, Q.Y.; Xu, M.K.; Liu, G.; Christoffersen, C.T.; Wang, M.W. Discovery of novel PDE10 inhibitors by a robust homogeneous screening assay. Acta Pharmacol. Sin., 2013, 34(8), 1116-1120.
[9]
Huang, W.; Zhang, Y.; Sportsman, J.R. A fluorescence polarization assay for cyclic nucleotide phosphodiesterases. J. Biomol. Screen., 2002, 7(3), 215-222.
[10]
Staeben, M.; Kleman-Leyer, K.M.; Kopp, A.L.; Westermeyer, T.A.; Lowery, R.G. Development and validation of a transcreener assay for detection of AMP- and GMP-producing enzymes. Assay Drug Dev. Technol., 2010, 8(3), 344-355.
[11]
Chen, C.; Liu, M.; Wu, J.; Yang, X.; Hu, X.; Pu, J.; Long, G.; Xie, Y.; Jiang, H.; Yuan, Y.; Liao, F. Microplate-based method to screen inhibitors of isozymes of cyclic nucleotide phosphodiesterase fused to SUMO. J. Enzyme Inhib. Med. Chem., 2014, 29(6), 836-839.
[12]
Feng, J.; Chen, Y.; Pu, J.; Yang, X.; Zhang, C.; Zhu, S.; Zhao, Y.; Yuan, Y.; Yuan, H.; Liao, F. An improved malachite green assay of phosphate: Mechanism and application. Anal. Biochem., 2011, 409(1), 144-149.
[13]
Zhu, S.; Gan, Z.; Li, Z.; Liu, Y.; Yang, X.; Deng, P.; Xie, Y.; Yu, M.; Liao, H.; Zhao, Y.; Zhao, L.; Liao, F. The measurement of cyclic nucleotide phosphodiesterase 4 activities via the quantification of inorganic phosphate with malachite green. Anal. Chim. Acta, 2009, 636(1), 105-110.
[14]
Arya, R.; Aslam, S.; Gupta, S.; Bora, R.S.; Vijayakrishnan, L.; Gulati, P.; Naithani, S.; Mukherjee, S.; Dastidar, S.; Bhattacharya, A.; Saini, K.S. Production and characterization of pharmacologically active recombinant human phosphodiesterase 4B in Dictyostelium discoideum. Biotechnol. J., 2008, 3(7), 938-947.
[15]
Saldou, N.; Obernolte, R.; Huber, A.; Baecker, P.A.; Wilhelm, R.; Alvarez, R.; Li, B.; Xia, L.; Callan, O.; Su, C.; Jarnagin, K.; Shelton, E.R. Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Cell. Signal., 1998, 10(6), 427-440.
[16]
Rocque, W.J.; Tian, G.; Wiseman, J.S.; Holmes, W.D.; Zajac-Thompson, I.; Willard, D.H.; Patel, I.R.; Wisely, G.B.; Clay, W.C.; Kadwell, S.H.; Hoffman, C.R.; Luther, M.A. Human recombinant phosphodiesterase 4B2B binds (R)-rolipram at a single site with two affinities. Biochemistry, 1997, 36(46), 14250-14261.
[17]
Rocque, W.J.; Holmes, W.D.; Patel, I.R.; Dougherty, R.W.; Ittoop, O.; Overton, L.; Hoffman, C.R.; Wisely, G.B.; Willard, D.H.; Luther, M.A. Detailed characterization of a purified type 4 phosphodiesterase.; HSPDE4B2B: Differentiation of high- and low-affinity (R)-rolipram binding. Protein Expr. Purif., 1997, 9(2), 191-202.
[18]
Wang, P.; Myers, J.G.; Wu, P.; Cheewatrakoolpong, B.; Egan, R.W.; Billah, M.M. Expression, purification, and characterization of human cAMP-specific phosphodiesterase (PDE4) subtypes A, B, C and D. Biochem. Biophys. Res. Commun., 1997, 234(2), 320-324.
[19]
Salanova, M.; Jin, S.C.; Conti, M. Heterologous expression and purification of recombinant rolipram-sensitive cyclic AMP-specific phosphodiesterases. Methods, 1998, 14(1), 55-64.
[20]
Gurney, M.E.; Burgin, A.B.; Magnusson, O.T.; Stewart, L.J. Small molecule allosteric modulators of phosphodiesterase 4. Handb. Exp. Pharmacol., 2011, (204), 167-192.
[21]
Xie, M.; Blackman, B.; Scheitrum, C.; Mika, D.; Blanchard, E.; Lei, T.; Conti, M.; Richter, W. The upstream conserved regions (UCRs) mediate homo- and hetero-oligomerization of type 4 cyclic nucleotide phosphodiesterases (PDE4s). Biochem. J., 2014, 459(3), 539-550.
[22]
Souness, J.E.; Rao, S. Proposal for pharmacologically distinct conformers of PDE4 cyclic AMP phosphodiesterases. Cell. Signal., 1997, 9(3-4), 227-236.
[23]
Zhu, S.; Yang, G.; Yang, X.; Zhao, Y.; Li, X.; Deng, P.; Xie, Y.; Gan, Z.; Liu, Y.; Li, Z.; Liao, J.; Yu, M.; Liao, F. Soluble expression in Escherichia coli of active human cyclic nucleotide phosphodiesterase isoform 4B2 in fusion with maltose-binding protein. Biosci. Biotechnol. Biochem., 2009, 73(4), 968-970.
[24]
Zhang, Y.; Yang, X.; Hu, X.; Liu, M.; Chen, C.; Xie, Y.; Pu, J.; Wu, J.; Long, G.; Liao, F. Resonant-Mie-scattering of aggregates of phosphomolybdate and papaverine for measuring activities and screening inhibitors of cyclic nucleotide phosphodiesterase isozymes. Anal. Chim. Acta, 2013, 804, 215-220.
[25]
Ashton, M.J.; Cook, D.C.; Fenton, G.; Karlsson, J.A.; Palfreyman, M.N.; Raeburn, D.; Ratcliffe, A.J.; Souness, J.E.; Thurairatnam, S.; Vicker, N. Selective type IV phosphodiesterase inhibitors as antiasthmatic agents.The syntheses and biological activities of 3-(cyclopentyloxy)-4-methoxybenzamides and analogues. J. Med. Chem., 1994, 37(11), 1696-1703.
[26]
Day, J.P.; Lindsay, B.; Riddell, T.; Jiang, Z.; Allcock, R.W.; Abraham, A.; Sookup, S.; Christian, F.; Bogum, J. Marti,n E.K.; Rae, R.L.; Anthony, D.; Rosair, G.M.; Houslay, D.M.; Huston, E.; Baillie, G.S.; Klussmann, E.; Houslay, M.D.; Adams, D.R. Elucidation of a structural basis for the inhibitor-driven, p62 (SQSTM1)-dependent intracellular redistribution of cAMP phosphodiesterase-4A4 (PDE4A4). J. Med. Chem., 2011, 54(9), 3331-3347.
[27]
Yuan, M.; Yang, X.; Li, Y.; Liu, H.; Pu, J.; Zhan, C.G.; Liao, F. Facile alkaline lysis of Echerichia coli cells in high-throughput mode for screening enzyme mutants: Arylsulfatase as an example. Appl. Biochem. Biotechnol., 2016, 179(4), 545-557.
[28]
Li, Y.; Yang, X.; Wang, D.; Hu, X.; Yuan, M.; Pu, J.; Zhan, C-G.; Yang, Z.; Liao, F. Striking effects of storage buffers on apparent half-lives of the activity of pseudomonas aeruginosa arylsulfatase. Protein J., 2016, 35(4), 283-290.
[29]
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 1976, 72, 248-254.
[30]
Qi, M.; Zhang, G.P. An investigation of model selection criteria for neural network time series forecasting. Eur. J. Oper. Res., 2001, 132(1), 666-680.
[31]
Li, Y.; Long, G.; Yang, X.; Hu, X.; Feng, Y.; Tan, D.; Xie, Y.; Pu, J.; Liao, F. Approximated maximum adsorption of His-tagged enzyme/mutants on Ni2+-NTA for comparison of specific activities. Int. J. Biol. Macromol., 2015, 74, 211-217.
[32]
You, C.; Okano, H.; Hui, S.; Zhang, Z.; Kim, M.; Gunderson, C.W.; Wang, Y.P.; Lenz, P. Ya,n D.; Hwa, T. Coordination of bacterial proteome with metabolism by cyclic AMP signalling. Nature, 2013, 500(7462), 301-306.
[33]
Malo, N.; Hanley, J.A.; Cerquozzi, S.; Pelletier, J.; Nadon, R. Statistical practice in high-throughput screening data analysis. Nat. Biotechnol., 2006, 24(2), 167-175.

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      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=8) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.13msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=8) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.12msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '97096'
      2.49msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 97096
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '97096'
      2.23msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 97096
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '97096' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      1.56msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 97096
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      240μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      440μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 8 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      26.56msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 8 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      16.69msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 8 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      13.74msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 97096 limit 1
      200μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 97096
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 97096 and content_type = 'article' order by status desc limit 1
      230μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 170481 limit 1
      170μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 170481
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      180μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CCHTS' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      260μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CCHTS
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '97096' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      300μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '9080' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      250μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '2539' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      230μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2539) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2539) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2539)
      1.34msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9080) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9080) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9080)
      510μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 97096) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 97096) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59235952 and j.to_ip >=59235952 )) and ((j.from_date <= 1740345515 and j.to_date >= 1740345515 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 97096)
      510μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '49' and is_uploaded = 1 and issue_id = 9080 order by cast(first_page as SIGNED) desc limit 1
      430μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 49
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '58' and is_uploaded = 1 and issue_id = 9080 order by cast(first_page as SIGNED) asc limit 1
      410μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 58
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      230μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      300μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 97096 limit 1
      2.51msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 97096
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 8 and `b`.`banner_from_date` <= 1740345515 and `b`.`banner_to_date` >= 1740345515 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.54msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 8
      • 3: 1740345515
      • 4: 1740345515
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 8 and `b`.`banner_from_date` <= 1740345515 and `b`.`banner_to_date` >= 1740345515 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.53msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 8
      • 3: 1740345515
      • 4: 1740345515
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='372492906e07e0e281bbabb635e593ec'
      280μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-23 21:18:35GET/article/97096314361