Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

miR-7 Reduces High Glucose Induced-damage Via HoxB3 and PI3K/AKT/mTOR Signaling Pathways in Retinal Pigment Epithelial Cells

Author(s): Zhongyi Yang, Hanying Hu, Yuling Zou, Wenbluo Luo, Lin Xie and Zhipeng You*

Volume 20, Issue 5, 2020

Page: [372 - 378] Pages: 7

DOI: 10.2174/1566524019666191023151137

Price: $65

Abstract

Background: Diabetic retinopathy (DR) is a common complication of diabetes. This study investigated the effect of miR-7 in the regulation of cell proliferation via the HoxB3 gene and PI3K/AKT/mTOR signaling pathways in DR.

Methods: Human retinal pigment epithelial cell line (ARPE-19) cultured in normal medium (Control) and high glucose medium (25mM glucose, HG) was transfected with mimics NC (HG+ mimics NC), miR-7 mimics (HG+miR-7 mimics), inhibitor NC (HG+ inhibitor NC), and miR-inhibitor (HG+miR-7 inhibitor). The cells were assayed for viability, apoptosis, and expression of genes.

Results: HG reduced cell viability and increased apoptosis. However, miR-7 mimics reduced the apoptosis. PCR results showed that miR-7 was significantly upregulated after transfection with miR-7 mimics. The expression of Hoxb3, mTOR, p-PI3K, and p- AKT was significantly downregulated at mRNA and protein levels after miR-7 mimics transfection, while no difference was observed for PI3K and AKT expression.

Conclusion: Our findings demonstrate that miR-7 regulates the growth of retinal epithelial cells through various pathways and is a potential therapeutic target for the prevention and treatment of diabetic retinopathy.

Keywords: miR-7, HoxB3, DR, PI3K/AKT/mTOR signaling, retinopathy, celll proliferation.

[1]
Weng JP, Bi Y. Epidemiological status of chronic diabetic complications in china. Chin Med J 2015; 128(24): 3267-9.
[http://dx.doi.org/10.4103/0366-6999.171350] [PMID: 26668138]
[2]
Vujosevic S, Midena E. Diabetic retinopathy in italy: epidemiology data and telemedicine screening programs. J Diabetes Res 2016; 2016 3627465
[http://dx.doi.org/10.1155/2016/3627465] [PMID: 27990441]
[3]
Lorenzi GM, Braffett BH, Arends VL, et al. Quality control measures over 30 years in a multicenter clinical study: results from the diabetes control and complications trial / epidemiology of diabetes interventions and complications (DCCT/EDIC) study. PLoS One 2015; 10(11) e0141286
[http://dx.doi.org/10.1371/journal.pone.0141286] [PMID: 26529311]
[4]
Mottaghi S, Larijani B, Sharifi AM. Atorvastatin: an efficient step forward in mesenchymal stem cell therapy of diabetic retinopathy. Cytotherapy 2013; 15(3): 263-6.
[http://dx.doi.org/10.1016/j.jcyt.2012.11.002] [PMID: 23253439]
[5]
Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. eLife 2015; 4: 4.
[http://dx.doi.org/10.7554/eLife.05005] [PMID: 26267216]
[6]
Zhou X, Zhu W, Li H, et al. Diagnostic value of a plasma microRNA signature in gastric cancer: a microRNA expression analysis. Sci Rep 2015; 5: 11251.
[http://dx.doi.org/10.1038/srep11251] [PMID: 26059512]
[7]
Wu JH, Gao Y, Ren AJ, et al. Altered microRNA expression profiles in retinas with diabetic retinopathy. Ophthalmic Res 2012; 47(4): 195-201.
[http://dx.doi.org/10.1159/000331992] [PMID: 22156553]
[8]
Currie KW, Brown DD, Zhu S, et al. HOX gene complement and expression in the planarian Schmidtea mediterranea. Evodevo 2016; 7: 7.
[http://dx.doi.org/10.1186/s13227-016-0044-8] [PMID: 27034770]
[9]
Platais C, Hakami F, Darda L, Lambert DW, Morgan R, Hunter KD. The role of HOX genes in head and neck squamous cell carcinoma. J Oral Pathol Med 2016; 45(4): 239-47.
[http://dx.doi.org/10.1111/jop.12388] [PMID: 26661059]
[10]
Hutlet B, Theys N, Coste C, et al. Systematic expression analysis of Hox genes at adulthood reveals novel patterns in the central nervous system. Brain Struct Funct 2016; 221(3): 1223-43.
[http://dx.doi.org/10.1007/s00429-014-0965-8] [PMID: 25527350]
[11]
Li Q, Zhu F, Chen P. miR-7 and miR-218 epigenetically control tumor suppressor genes RASSF1A and Claudin-6 by targeting HoxB3 in breast cancer. Biochem Biophys Res Commun 2012; 424(1): 28-33.
[http://dx.doi.org/10.1016/j.bbrc.2012.06.028] [PMID: 22705304]
[12]
Li YZ, Wen L, Wei X, et al. Inhibition of miR-7 promotes angiogenesis in human umbilical vein endothelial cells by upregulating VEGF via KLF4. Oncol Rep 2016; 36(3): 1569-75.
[http://dx.doi.org/10.3892/or.2016.4912] [PMID: 27431648]
[13]
Wei LZ, Wang YQ, Chang YL, et al. Imbalance of a KLF4-miR-7 auto-regulatory feedback loop promotes prostate cancer cell growth by impairing microRNA processing. Am J Cancer Res 2018; 8(2): 226-44.
[PMID: 29511594]
[14]
Senthilkumari S, Sharmila R, Chidambaranathan G, Vanniarajan A. Epalrestat, an aldose reductase inhibitor prevents glucose-induced toxicity in human retinal pigment epithelial cells in vitro. J Ocul Pharmacol Ther 2017; 33(1): 34-41.
[http://dx.doi.org/10.1089/jop.2016.0103] [PMID: 27835059]
[15]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[16]
Shadrach KG, Rayborn ME, Hollyfield JG, Bonilha VL. Correction: DJ-1-dependent regulation of oxidative stress in the retinal pigment epithelium (RPE). PLoS One 2017; 12(10) e0185834
[http://dx.doi.org/10.1371/journal.pone.0185834] [PMID: 28968455]
[17]
Li KR, Yang SQ, Gong YQ, et al. 3H-1,2-dithiole-3-thione protects retinal pigment epithelium cells against Ultra-violet radiation via activation of Akt-mTORC1-dependent Nrf2-HO-1 signaling. Sci Rep 2016; 6: 25525.
[http://dx.doi.org/10.1038/srep25525] [PMID: 27151674]
[18]
Chen XL, Zhang XD, Li YY, Chen XM, Tang DR, Ran RJ. Involvement of HMGB1 mediated signalling pathway in diabetic retinopathy: evidence from type 2 diabetic rats and ARPE-19 cells under diabetic condition. Br J Ophthalmol 2013; 97(12): 1598-603.
[http://dx.doi.org/10.1136/bjophthalmol-2013-303736] [PMID: 24133029]
[19]
Oh JR, Han JW, Kim YK, Ohn YH, Park TK. The effects of anti-vascular endothelial growth factor agents on human retinal pigment epithelial cells under high glucose conditions. Int J Ophthalmol 2017; 10(2): 203-10.
[PMID: 28251077]
[20]
Takagi H, Tanihara H, Seino Y, Yoshimura N. Characterization of glucose transporter in cultured human retinal pigment epithelial cells: gene expression and effect of growth factors. Invest Ophthalmol Vis Sci 1994; 35(1): 170-7.
[PMID: 8300344]
[21]
Young TA, Wang H, Munk S, et al. Vascular endothelial growth factor expression and secretion by retinal pigment epithelial cells in high glucose and hypoxia is protein kinase C-dependent. Exp Eye Res 2005; 80(5): 651-62.
[http://dx.doi.org/10.1016/j.exer.2004.11.015] [PMID: 15862172]
[22]
Chen H, Fan Y, Xu W, et al. miR-10b inhibits apoptosis and promotes proliferation and invasion of endometrial cancer cells via targeting HOXB3. Cancer Biother Radiopharm 2016; 31(6): 225-31.
[http://dx.doi.org/10.1089/cbr.2016.1998] [PMID: 27447302]
[23]
Yang D, Yan R, Zhang X, et al. Deregulation of MicroRNA-375 inhibits cancer proliferation migration and chemosensitivity in pancreatic cancer through the association of HOXB3. Am J Transl Res 2016; 8(3): 1551-9.
[PMID: 27186281]
[24]
Arevalo JF, Liu TYA. Intravitreal bevacizumab in diabetic retinopathy. Recommendations from the pan-american collaborative retina study group (PACORES): The 2016 knobloch lecture. Asia Pac J Ophthalmol (Phila) 2018; 7(1): 36-9.
[PMID: 29280367]
[25]
Ma J, Wang J, Liu Y, et al. Comparisons of serum miRNA expression profiles in patients with diabetic retinopathy and type 2 diabetes mellitus. Clinics (São Paulo) 2017; 72(2): 111-5.
[http://dx.doi.org/10.6061/clinics/2017(02)08] [PMID: 28273235]
[26]
Choudhary GS, Al-Harbi S, Mazumder S, et al. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis 2015; 6 e1593
[http://dx.doi.org/10.1038/cddis.2014.525] [PMID: 25590803]
[27]
Jacot JL, Sherris D. Potential therapeutic roles for inhibition of the PI3K/Akt/mTOR pathway in the pathophysiology of diabetic retinopathy. J Ophthalmol 2011; 2011 589813
[http://dx.doi.org/10.1155/2011/589813] [PMID: 22132311]
[28]
Xiong X, Wang P, Zhang Y, et al. Effects of traditional Chinese patent medicine on essential hypertension: a systematic review. Medicine (Baltimore) 2015; 94(5) e442
[29]
Chen X, Li J, Li M, et al. KH902 suppresses high glucose-induced migration and sprouting of human retinal endothelial cells by blocking VEGF and PIGF. Diabetes Obes Metab 2013; 15(3): 224-33.
[http://dx.doi.org/10.1111/dom.12008] [PMID: 22958404]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version264msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[21:42:46] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[21:42:46] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[21:42:46] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (92.5ms)time
  • Application (172ms)time
  • 1 x Application (65%)
    172ms
    1 x Booting (35%)
    92.50ms
    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 duplicated98.56ms
    • 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 ('59559709','',1,1740346966,1740346966) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740346966
      1.14msalphaeurekaselec_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 ('59559709','/article/101834',1,1740346966,1740346966)
      210μsalphaeurekaselec_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 >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) 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 >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) 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 >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) 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 >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) 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 >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) 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 >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 59559709 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 59559709) limit 1
      11.98msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 59559709
      • 1: 59559709
      • 2: 59559709
      • 3: 59559709
      • 4: 59559709
      • 5: 59559709
      • 6: 59559709
      • 7: 59559709
      • 8: 59559709
      • 9: 59559709
      • 10: 59559709
      • 11: 59559709
      • 12: 59559709
      • 13: 59559709
      • 14: 59559709
      • 15: 59559709
      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=101834
      710μsalphaeurekaselec_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` = 23 limit 1
      870μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 23
      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=23) and sj.journal_id!=23 group by `j`.`nid`) as `aggregate_table`
      870μsalphaeurekaselec_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=23) and sj.journal_id!=23 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      790μsalphaeurekaselec_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=23) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.72msalphaeurekaselec_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=23) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.85msalphaeurekaselec_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` = '101834'
      950μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 101834
      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` = '101834'
      3.22msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 101834
      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` = '101834' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.41msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 101834
      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
      220μsalphaeurekaselec_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
      430μsalphaeurekaselec_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 = 23 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      26.01msalphaeurekaselec_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 = 23 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      10.25msalphaeurekaselec_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 = 23 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      9.05msalphaeurekaselec_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` = 101834 limit 1
      240μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 101834
      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 = 101834 and content_type = 'article' order by status desc limit 1
      270μsalphaeurekaselec_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` = 176094 limit 1
      180μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 176094
      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
      200μsalphaeurekaselec_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` = 'CMM' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      290μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CMM
      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 = '101834' 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) )
      330μsalphaeurekaselec_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 = '9689' 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) )
      280μsalphaeurekaselec_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 = '2689' 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) )
      390μsalphaeurekaselec_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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2689) 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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2689) 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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2689)
      12.24msalphaeurekaselec_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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9689) 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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9689) 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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9689)
      870μsalphaeurekaselec_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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 101834) 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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 101834) 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 <= 59559709 and j.to_ip >=59559709 )) and ((j.from_date <= 1740346966 and j.to_date >= 1740346966 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 101834)
      780μsalphaeurekaselec_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` < '372' and is_uploaded = 1 and issue_id = 9689 order by cast(first_page as SIGNED) desc limit 1
      580μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 372
      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` > '378' and is_uploaded = 1 and issue_id = 9689 order by cast(first_page as SIGNED) asc limit 1
      550μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 378
      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
      240μsalphaeurekaselec_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` = 101834 limit 1
      2.8msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 101834
      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` = 23 and `b`.`banner_from_date` <= 1740346966 and `b`.`banner_to_date` >= 1740346966 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.6msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 23
      • 3: 1740346966
      • 4: 1740346966
      • 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` = 23 and `b`.`banner_from_date` <= 1740346966 and `b`.`banner_to_date` >= 1740346966 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.56msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 23
      • 3: 1740346966
      • 4: 1740346966
      • 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='cd8036e43cbe49650ea9c7c81d702746'
      270μsalphaeurekaselec_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#?
    App\Models\MultiLangArticle
    1MultiLangArticle.php#?
        _token
        qVcJYtdZFcKSmxdf8mR9DLeu4ln7lqjCHCHN0PH2
        uc_cart_id
        cd8036e43cbe49650ea9c7c81d702746
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/101834" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/101834
        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 => "Sun, 23 Feb 2025 21:42:46 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImF5S3ZDTzV3WGJUalFwU2ZSNDlubmc9PSIsInZhbHVlIjoiM0VrTXR5UU9TTTkzdTRFb00xYlYvTEkyL0ZGUm5MdGxRZG4yNlFuSWZjam82dFN4blhaRkZVS2dpRXVhckF2N1dnU3VZR2xmbm1RczR5SzA3Mlc1NTNUYWIweWM0OWYxVFFOdnJyZHZBRzJHM3E2SXVhVXIwUjBoNWhPVExiOGciLCJtYWMiOiJhNmRiNTlhOWIxNjU5ZDBkNDg5ZjVkYmRkNDAzZmM2NmFjMGIyMGJjMThjYzY1MTk1NjZmZDY3MzNhYmI0ZDYwIiwidGFnIjoiIn0%3D; expires=Wed, 26 Feb 2025 09:42:46 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6ImF5S3ZDTzV3WGJUalFwU2ZSNDlubmc9PSIsInZhbHVlIjoiM0VrTXR5UU9TTTkzdTRFb00xYlYvTEkyL0ZGUm5MdGxRZG4yNlFuSWZjam82dFN4blhaRkZVS2dpRXVhckF2N1dnU3VZR" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ilo5cnBmUGtJVHI5UXRZTEp5T1ZUTEE9PSIsInZhbHVlIjoiTURLNEpSV0kvNWNvVW9tWjVkWHFSODFSNjBPTnFmc0NIN2JrVFRndHBmbDFwL1ZmVHpLQmF1SDY4TFZFa0VUQUR2Z21Jd3dlZkJPMnZCc2xPNXFxNzhlSUYwVk56b3JaMjROTktqdGdTUjNCamlEaVBTUzBGZ3NDNWFjeWc3MVoiLCJtYWMiOiJiYmQ5ZTM1ZWVmMDcwMmFlMWM1ZTczNWM1YTgwZTUyZjU3YWFiM2NiNWRlYTllOGUxMzdkYWViOTNjOWViNGQ3IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6Ilo5cnBmUGtJVHI5UXRZTEp5T1ZUTEE9PSIsInZhbHVlIjoiTURLNEpSV0kvNWNvVW9tWjVkWHFSODFSNjBPTnFmc0NIN2JrVFRndHBmbDFwL1ZmVHpLQmF1SDY" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6ImF5S3ZDTzV3WGJUalFwU2ZSNDlubmc9PSIsInZhbHVlIjoiM0VrTXR5UU9TTTkzdTRFb00xYlYvTEkyL0ZGUm5MdGxRZG4yNlFuSWZjam82dFN4blhaRkZVS2dpRXVhckF2N1dnU3VZR2xmbm1RczR5SzA3Mlc1NTNUYWIweWM0OWYxVFFOdnJyZHZBRzJHM3E2SXVhVXIwUjBoNWhPVExiOGciLCJtYWMiOiJhNmRiNTlhOWIxNjU5ZDBkNDg5ZjVkYmRkNDAzZmM2NmFjMGIyMGJjMThjYzY1MTk1NjZmZDY3MzNhYmI0ZDYwIiwidGFnIjoiIn0%3D; expires=Wed, 26-Feb-2025 09:42:46 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6ImF5S3ZDTzV3WGJUalFwU2ZSNDlubmc9PSIsInZhbHVlIjoiM0VrTXR5UU9TTTkzdTRFb00xYlYvTEkyL0ZGUm5MdGxRZG4yNlFuSWZjam82dFN4blhaRkZVS2dpRXVhckF2N1dnU3VZR" 1 => "alphaeurekaselectnet_session=eyJpdiI6Ilo5cnBmUGtJVHI5UXRZTEp5T1ZUTEE9PSIsInZhbHVlIjoiTURLNEpSV0kvNWNvVW9tWjVkWHFSODFSNjBPTnFmc0NIN2JrVFRndHBmbDFwL1ZmVHpLQmF1SDY4TFZFa0VUQUR2Z21Jd3dlZkJPMnZCc2xPNXFxNzhlSUYwVk56b3JaMjROTktqdGdTUjNCamlEaVBTUzBGZ3NDNWFjeWc3MVoiLCJtYWMiOiJiYmQ5ZTM1ZWVmMDcwMmFlMWM1ZTczNWM1YTgwZTUyZjU3YWFiM2NiNWRlYTllOGUxMzdkYWViOTNjOWViNGQ3IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6Ilo5cnBmUGtJVHI5UXRZTEp5T1ZUTEE9PSIsInZhbHVlIjoiTURLNEpSV0kvNWNvVW9tWjVkWHFSODFSNjBPTnFmc0NIN2JrVFRndHBmbDFwL1ZmVHpLQmF1SDY" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "qVcJYtdZFcKSmxdf8mR9DLeu4ln7lqjCHCHN0PH2" "uc_cart_id" => "cd8036e43cbe49650ea9c7c81d702746" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/101834" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-23 21:42:46GET/article/101834314362