Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Construction of GPC3-modified Lipopolymer SiRNA Delivery System

Author(s): Dandan Sun, Xiaoyu Li, Yaru Liu, Jishan Quan* and Guangyu Jin*

Volume 30, Issue 19, 2024

Published on: 19 April, 2024

Page: [1507 - 1518] Pages: 12

DOI: 10.2174/0113816128258852231204102044

Price: $65

Abstract

Background: Gene therapy has been widely concerned because of its unique therapeutic mechanism. However, due to the lack of safe and effective carries, it has not been widely used in clinical practice. Glypican 3 (GPC3) is a highly specific proteoglycan for hepatocellular carcinoma and is a potential diagnostic and therapeutic target for hepatocellular carcinoma. Herein, to monitor the effect of gene therapy and enhance the transfection efficiency of gene carriers, GPC3-modified lipid polyethyleneimine-modified superparamagnetic nanoparticle (GLPS), a type of visualized carrier for siRNA (small-interfering RNA) targeting the liver, was prepared.

Methods: We performed in vitro gene silencing, cytotoxicity, and agarose gel electrophoresis to identify the optimal GLPS formulation. In vitro MRI and Prussian blue staining verified the liver-targeting function of GLPS. We also analyzed the biocompatibility of GLPS by co-culturing with rabbit red blood cells. Morphological changes were evaluated using HE staining.

Results: The GLPS optimal formulation consisted of LPS and siRNA at a mass ratio of 25:1 and LPS and DSPE-PEG-GPC3 at a molar ratio of 2:3. GLPS exhibited evident liver-targeting function. In vitro, we did not observe morphological changes in red blood cells or hemolysis after co-culture. In vivo, routine blood analysis revealed no abnormalities after GLPS injection. Moreover, the tissue morphology of the kidney, spleen, and liver was normal without injury or inflammation.

Conclusion: GLPS could potentially serve as an effective carrier for liver-targeted MRI monitoring and siRNA delivery.

[1]
Asafo-Agyei KO, Samant H. Hepatocellular carcinoma. Treasure Island, FL: StatPearls 2022.
[2]
Sahin ID, Christodoulou MS, Guzelcan EA, et al. A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition. Sci Rep 2020; 10(1): 11814.
[http://dx.doi.org/10.1038/s41598-020-68775-9] [PMID: 32678233]
[3]
Cavazzana-Calvo M, Thrasher A, Mavilio F. The future of gene therapy. Nature 2004; 427(6977): 779-81.
[http://dx.doi.org/10.1038/427779a] [PMID: 14985734]
[4]
Kaiser J. Clinical research. Gene therapists celebrate a decade of progress. Science 2011; 334(6052): 29-30.
[http://dx.doi.org/10.1126/science.334.6052.29] [PMID: 21980087]
[5]
Zhao Y, Zhao T, Du Y, et al. Interaction kinetics of peptide lipids- mediated gene delivery. J Nanobiotechnol 2020; 18(1): 144.
[http://dx.doi.org/10.1186/s12951-020-00707-1] [PMID: 33069258]
[6]
Lundstrom K. Viral vectors in gene therapy: Where do we stand in 2023? Viruses 2023; 15(3): 698.
[http://dx.doi.org/10.3390/v15030698] [PMID: 36992407]
[7]
Sun D, Jin G, Jin Z, et al. Construction of a visualized liver-targeting siRNA delivery system. J Drug Deliv Sci Technol 2023; 85: 104566.
[http://dx.doi.org/10.1016/j.jddst.2023.104566]
[8]
Lu Y, Li J, Su N, Lu D. The mechanism for siRNA transmembrane assisted by PMAL. Molecules 2018; 23(7): 1586.
[http://dx.doi.org/10.3390/molecules23071586] [PMID: 29966273]
[9]
Zu H, Gao D. Non-viral vectors in gene therapy: Recent development, challenges, and prospects. AAPS J 2021; 23(4): 78.
[http://dx.doi.org/10.1208/s12248-021-00608-7] [PMID: 34076797]
[10]
Mirzaei S, Paskeh MDA, Entezari M, et al. siRNA and targeted delivery systems in breast cancer therapy. Clin Transl Oncol 2022; 25(5): 1167-88.
[http://dx.doi.org/10.1007/s12094-022-03043-y] [PMID: 36562927]
[11]
Li D, Gao C, Kuang M, et al. Nanoparticles as drug delivery systems of RNAi in cancer therapy. Molecules 2021; 26(8): 2380.
[http://dx.doi.org/10.3390/molecules26082380] [PMID: 33921892]
[12]
Duan Y, Guan X, Ge J, et al. Cationic nano-copolymers mediated IKKbeta targeting siRNA inhibit the proliferation of human Tenon’s capsule fibroblasts in vitro. Mol Vis 2008; 14: 2616-28.
[PMID: 19137061]
[13]
Sánchez-Moreno P, de Vicente J, Nardecchia S, Marchal J, Boulaiz H. Thermo-sensitive nanomaterials: Recent advance in synthesis and biomedical applications. Nanomaterials 2018; 8(11): 935.
[http://dx.doi.org/10.3390/nano8110935] [PMID: 30428608]
[14]
Mellott AJ, Shinogle HE, Moore DS, Detamore MS. Fluorescent Photo-conversion: A second chance to label unique cells. Cell Mol Bioeng 2015; 8(1): 187-96.
[http://dx.doi.org/10.1007/s12195-014-0365-4] [PMID: 25914756]
[15]
Chen Z, Krishnamachary B, Bhujwalla Z. Degradable dextran nanopolymer as a carrier for Choline Kinase (ChoK) siRNA cancer therapy. Nanomaterials 2016; 6(2): 34.
[http://dx.doi.org/10.3390/nano6020034] [PMID: 28344291]
[16]
Sun W, Wang Y, Cai M, et al. Codelivery of sorafenib and GPC3 siRNA with PEI-modified liposomes for hepatoma therapy. Biomater Sci 2017; 5(12): 2468-79.
[http://dx.doi.org/10.1039/C7BM00866J] [PMID: 29106433]
[17]
Zhang L, Chan JM, Gu FX, et al. Self-assembled lipid-polymer hybrid nanoparticles: A robust drug delivery platform. ACS Nano 2008; 2(8): 1696-702.
[http://dx.doi.org/10.1021/nn800275r] [PMID: 19206374]
[18]
García L, Buñuales M, Düzgüneş N, Tros de Ilarduya C. Serum-resistant lipopolyplexes for gene delivery to liver tumour cells. Eur J Pharm Biopharm 2007; 67(1): 58-66.
[http://dx.doi.org/10.1016/j.ejpb.2007.01.005] [PMID: 17321729]
[19]
Wang J, Ye X, Ni H, Zhang J, Ju S, Ding W. Transfection efficiency evaluation and endocytosis exploration of different polymer condensed agents. DNA Cell Biol 2019; 38(10): 1048-55.
[http://dx.doi.org/10.1089/dna.2018.4464] [PMID: 31433200]
[20]
Ewe A, Panchal O, Pinnapireddy SR, et al. Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo. Nanomedicine 2017; 13(1): 209-18.
[http://dx.doi.org/10.1016/j.nano.2016.08.005] [PMID: 27553077]
[21]
Lungwitz U, Breunig M, Blunk T, Göpferich A. Polyethylenimine-based non-viral gene delivery systems. Eur J Pharm Biopharm 2005; 60(2): 247-66.
[http://dx.doi.org/10.1016/j.ejpb.2004.11.011] [PMID: 15939236]
[22]
Shih TC, Wang L, Wang HC, Wan YJY. Glypican-3: A molecular marker for the detection and treatment of hepatocellular carcinoma. Liver Res 2020; 4(4): 168-72.
[http://dx.doi.org/10.1016/j.livres.2020.11.003] [PMID: 33384879]
[23]
An S, Zhang D, Zhang Y, et al. GPC3-targeted immunoPET imaging of hepatocellular carcinomas. Eur J Nucl Med Mol Imaging 2022; 49(8): 2682-92.
[http://dx.doi.org/10.1007/s00259-022-05723-x] [PMID: 35147737]
[24]
Montalbano M, Georgiadis J, Masterson AL, et al. Biology and function of glypican-3 as a candidate for early cancerous transformation of hepatocytes in hepatocellular carcinoma. Oncol Rep 2017; 37(3): 1291-300.
[http://dx.doi.org/10.3892/or.2017.5387] [PMID: 28098909]
[25]
Lai JP, Oseini AM, Moser CD, et al. The oncogenic effect of sulfatase 2 in human hepatocellular carcinoma is mediated in part by glypican 3-dependent Wnt activation. Hepatology 2010; 52(5): 1680-9.
[http://dx.doi.org/10.1002/hep.23848] [PMID: 20725905]
[26]
Liu S, Li Y, Chen W, et al. Silencing glypican-3 expression induces apoptosis in human hepatocellular carcinoma cells. Biochem Biophys Res Commun 2012; 419(4): 656-61.
[http://dx.doi.org/10.1016/j.bbrc.2012.02.069] [PMID: 22382024]
[27]
Xing M, Wang X, Kirken R, He L, Zhang JY. Immunodiagnostic biomarkers for Hepatocellular Carcinoma (HCC): The first step in detection and treatment. Int J Mol Sci 2021; 22(11): 6139.
[http://dx.doi.org/10.3390/ijms22116139] [PMID: 34200243]
[28]
Zheng X, Liu X, Lei Y, Wang G, Liu M. Glypican-3: A novel and promising target for the treatment of hepatocellular carcinoma. Front Oncol 2022; 12: 824208.
[http://dx.doi.org/10.3389/fonc.2022.824208] [PMID: 35251989]
[29]
Sun J, Zhou Y, Jin G, Jin Y, Quan J. Preparation and preliminary evaluation of dual-functional nanoparticles for MRI and siRNA delivery. Iran J Pharm Res 2021; 20(4): 265-77.
[PMID: 35194445]
[30]
Yoo MK, Park IK, Lim HT, et al. Folate-PEG-superparamagnetic iron oxide nanoparticles for lung cancer imaging. Acta Biomater 2012; 8(8): 3005-13.
[http://dx.doi.org/10.1016/j.actbio.2012.04.029] [PMID: 22543005]
[31]
Ghaffari M, Dehghan G, Abedi-Gaballu F, et al. Surface functionalized dendrimers as controlled-release delivery nanosystems for tumor targeting. Eur J Pharm Sci 2018; 122: 311-30.
[http://dx.doi.org/10.1016/j.ejps.2018.07.020] [PMID: 30003954]
[32]
Bhatt H, Kiran Rompicharla SV, Ghosh B, Torchilin V, Biswas S. Transferrin/α-tocopherol modified poly(amidoamine) dendrimers for improved tumor targeting and anticancer activity of paclitaxel. Nanomedicine 2019; 14(24): 3159-76.
[http://dx.doi.org/10.2217/nnm-2019-0128] [PMID: 31855118]
[33]
Chouly C, Pouliquen D, Lucet I, Jeune JJ, Jallet P. Development of superparamagnetic nanoparticles for MRI: Effect of particle size, charge and surface nature on biodistribution. J Microencapsul 1996; 13(3): 245-55.
[http://dx.doi.org/10.3109/02652049609026013] [PMID: 8860681]
[34]
Harris JM, Chess RB. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2003; 2(3): 214-21.
[http://dx.doi.org/10.1038/nrd1033] [PMID: 12612647]
[35]
Yamazaki Y, Nango M, Matsuura M, Hasegawa Y, Hasegawa M, Oku N. Polycation liposomes, a novel nonviral gene transfer system, constructed from cetylated polyethylenimine. Gene Ther 2000; 7(13): 1148-55.
[http://dx.doi.org/10.1038/sj.gt.3301217] [PMID: 10918482]
[36]
Nieto González N, Obinu A, Rassu G, Giunchedi P, Gavini E. Polymeric and lipid nanoparticles: Which applications in pediatrics? Pharmaceutics 2021; 13(5): 670.
[http://dx.doi.org/10.3390/pharmaceutics13050670] [PMID: 34066953]
[37]
Liu X, Gao F, Jiang L, et al. 32A9, a novel human antibody for designing an immunotoxin and CAR-T cells against glypican-3 in hepatocellular carcinoma. J Transl Med 2020; 18(1): 295.
[http://dx.doi.org/10.1186/s12967-020-02462-1] [PMID: 32746924]
[38]
Kostevšek N, Cheung CCL, Serša I, et al. Magneto-liposomes as MRI contrast agents: A systematic study of different liposomal formulations. Nanomaterials 2020; 10(5): 889.
[http://dx.doi.org/10.3390/nano10050889] [PMID: 32384645]
[39]
Wang B, Wu W, Lu H, Wang Z, Xin H. Enhanced anti-tumor of pep-1 modified superparamagnetic iron oxide/ptx loaded polymer nanoparticles. Front Pharmacol 2019; 9: 1556.
[http://dx.doi.org/10.3389/fphar.2018.01556] [PMID: 30723412]
[40]
Amin K, Dannenfelser RM. In vitro hemolysis: Guidance for the pharmaceutical scientist. J Pharm Sci 2006; 95(6): 1173-6.
[http://dx.doi.org/10.1002/jps.20627] [PMID: 16639718]
[41]
Zhang H. Preparation and Preliminary Evaluation of Glycosaminoglycans Modified Superparamagnetic Iron Oxide Nanoparticles as MRI Negative Contrast Agents. Shandong China: Shandong University 2020.
[42]
Singh N, Sahoo SK, Kumar R. Hemolysis tendency of anticancer nanoparticles changes with type of blood group antigen: An insight into blood nanoparticle interactions. Mater Sci Eng C 2020; 109: 110645.
[http://dx.doi.org/10.1016/j.msec.2020.110645] [PMID: 32228982]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version519msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[13:31:40] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[13:31:40] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[13:31:40] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[13:31:40] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[13:31:40] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (145ms)time
  • Application (374ms)time
  • 1 x Application (72.09%)
    374ms
    1 x Booting (27.91%)
    145ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated272ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('59884719','',1,1739971900,1739971900) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739971900
      1.73msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('59884719','/article/139892',1,1739971900,1739971900)
      3.03msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59884719 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59884719) limit 1
      16.19msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59884719
      • 1: 59884719
      • 2: 59884719
      • 3: 59884719
      • 4: 59884719
      • 5: 59884719
      • 6: 59884719
      • 7: 59884719
      • 8: 59884719
      • 9: 59884719
      • 10: 59884719
      • 11: 59884719
      • 12: 59884719
      • 13: 59884719
      • 14: 59884719
      • 15: 59884719
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=139892
      1.09msalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 29 limit 1
      1.26msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 29
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 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 count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and sj.journal_id!=29 group by `j`.`nid`) as `aggregate_table`
      1.59msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 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 j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=29) and sj.journal_id!=29 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.33msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 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 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=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.68msalphaeurekaselec_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=29) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.57msalphaeurekaselec_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` = '139892'
      340μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 139892
      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` = '139892'
      3.99msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 139892
      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` = '139892' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.75msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 139892
      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
      310μsalphaeurekaselec_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
      700μsalphaeurekaselec_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 = 29 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      64.64msalphaeurekaselec_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 = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      102msalphaeurekaselec_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 = 29 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      47.06msalphaeurekaselec_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` = 139892 limit 1
      270μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 139892
      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 = 139892 and content_type = 'article' order by status desc limit 1
      280μsalphaeurekaselec_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` = 229161 limit 1
      240μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 229161
      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
      270μsalphaeurekaselec_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` = 'CPD' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      450μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPD
      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 = '139892' 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) )
      480μsalphaeurekaselec_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 = '13349' 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) )
      360μsalphaeurekaselec_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 = '3494' 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) )
      440μsalphaeurekaselec_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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3494) 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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3494) 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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3494)
      8.75msalphaeurekaselec_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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13349) 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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13349) 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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13349)
      630μsalphaeurekaselec_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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 139892) 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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 139892) 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 <= 59884719 and j.to_ip >=59884719 )) and ((j.from_date <= 1739971900 and j.to_date >= 1739971900 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 139892)
      610μsalphaeurekaselec_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` < '1507' and is_uploaded = 1 and issue_id = 13349 order by cast(first_page as SIGNED) desc limit 1
      670μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 1507
      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` > '1518' and is_uploaded = 1 and issue_id = 13349 order by cast(first_page as SIGNED) asc limit 1
      600μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 1518
      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'
      210μsalphaeurekaselec_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
      220μsalphaeurekaselec_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` = 139892 limit 1
      2.53msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 139892
      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` = 29 and `b`.`banner_from_date` <= 1739971900 and `b`.`banner_to_date` >= 1739971900 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.65msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1739971900
      • 4: 1739971900
      • 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` = 29 and `b`.`banner_from_date` <= 1739971900 and `b`.`banner_to_date` >= 1739971900 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.66msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 29
      • 3: 1739971900
      • 4: 1739971900
      • 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='b0ea1e18c666994b271ea0826cddebe6'
      310μsalphaeurekaselec_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
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        NJLkolgQ2cQmvn0cy3InplsTf8yOe94jI2lvL3W8
        uc_cart_id
        b0ea1e18c666994b271ea0826cddebe6
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/139892" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/139892
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 13:31:40 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImZTOGVCd1RwSUlrTlY3OVNxZ2hkRnc9PSIsInZhbHVlIjoiaVczMVV4WGFkdzV1VjBJY0wvVmorZzlkQTcwNDNoSElIbDJWRHVSRWtaQXVrU2gzMndiVW4yVm1aN2s1TGtMcXh1NWFnZkRZODZTOXVLeWhYdHR0WDlDMnZuay9mTXJGYk4zNGIwb1lHbHhVbURUYmUwLzdqcEpNdGljZDZIMisiLCJtYWMiOiIyMGJmMDFmNWYxNmUzMzQ2YjlmMzY0OGU2ZTYzMTcwOTE0ZWI2ZTBlOTUzYWNiYTc5MGIxNGQ1OTZlNDY1NTJkIiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 01:31:40 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6ImZTOGVCd1RwSUlrTlY3OVNxZ2hkRnc9PSIsInZhbHVlIjoiaVczMVV4WGFkdzV1VjBJY0wvVmorZzlkQTcwNDNoSElIbDJWRHVSRWtaQXVrU2gzMndiVW4yVm1aN2s1TGtMcXh1NWFnZ" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImFWeTB4RFlJb3FqdmNTM29KeVd1QVE9PSIsInZhbHVlIjoiSWFmSldoRUkwWndBZ2NGZndqNlVyR0ZUcnJSMC95T2JSS2pJZXNtbzBEM2xyV29KWWF3L3dnT011cTZFcG1iOFp5dmhRL3RBQlR0NEcrOG9QL3BEbUxyc2wySm1hUFB0Rkd6OHNINWIrS2hVOXlWK2czUHE2QTRGZXdFL08yODQiLCJtYWMiOiI5OTcwNzZjMTdkYmQzNzUxMGI2YTZkMDlhNWUyZWJmYzFlMWUyNDY1ZWFmOWQ2ZjNhOTViYjgxMmY1ODFmMDBmIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImFWeTB4RFlJb3FqdmNTM29KeVd1QVE9PSIsInZhbHVlIjoiSWFmSldoRUkwWndBZ2NGZndqNlVyR0ZUcnJSMC95T2JSS2pJZXNtbzBEM2xyV29KWWF3L3dnT01" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImZTOGVCd1RwSUlrTlY3OVNxZ2hkRnc9PSIsInZhbHVlIjoiaVczMVV4WGFkdzV1VjBJY0wvVmorZzlkQTcwNDNoSElIbDJWRHVSRWtaQXVrU2gzMndiVW4yVm1aN2s1TGtMcXh1NWFnZkRZODZTOXVLeWhYdHR0WDlDMnZuay9mTXJGYk4zNGIwb1lHbHhVbURUYmUwLzdqcEpNdGljZDZIMisiLCJtYWMiOiIyMGJmMDFmNWYxNmUzMzQ2YjlmMzY0OGU2ZTYzMTcwOTE0ZWI2ZTBlOTUzYWNiYTc5MGIxNGQ1OTZlNDY1NTJkIiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 01:31:40 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6ImZTOGVCd1RwSUlrTlY3OVNxZ2hkRnc9PSIsInZhbHVlIjoiaVczMVV4WGFkdzV1VjBJY0wvVmorZzlkQTcwNDNoSElIbDJWRHVSRWtaQXVrU2gzMndiVW4yVm1aN2s1TGtMcXh1NWFnZ" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImFWeTB4RFlJb3FqdmNTM29KeVd1QVE9PSIsInZhbHVlIjoiSWFmSldoRUkwWndBZ2NGZndqNlVyR0ZUcnJSMC95T2JSS2pJZXNtbzBEM2xyV29KWWF3L3dnT011cTZFcG1iOFp5dmhRL3RBQlR0NEcrOG9QL3BEbUxyc2wySm1hUFB0Rkd6OHNINWIrS2hVOXlWK2czUHE2QTRGZXdFL08yODQiLCJtYWMiOiI5OTcwNzZjMTdkYmQzNzUxMGI2YTZkMDlhNWUyZWJmYzFlMWUyNDY1ZWFmOWQ2ZjNhOTViYjgxMmY1ODFmMDBmIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImFWeTB4RFlJb3FqdmNTM29KeVd1QVE9PSIsInZhbHVlIjoiSWFmSldoRUkwWndBZ2NGZndqNlVyR0ZUcnJSMC95T2JSS2pJZXNtbzBEM2xyV29KWWF3L3dnT01" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "NJLkolgQ2cQmvn0cy3InplsTf8yOe94jI2lvL3W8" "uc_cart_id" => "b0ea1e18c666994b271ea0826cddebe6" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/139892" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 13:31:40GET/article/139892514361