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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Epigenetic Regulator Signatures in Regenerative Capacity

Author(s): Sarah Albogami*

Volume 14, Issue 7, 2019

Page: [598 - 606] Pages: 9

DOI: 10.2174/1574888X14666190618125111

Price: $65

Abstract

Background: Regeneration is the process by which body parts lost as a result of injury are replaced, as observed in certain animal species. The root of regenerative differences between organisms is still not very well understood; if regeneration merely recycles developmental pathways in the adult form, why can some animals regrow organs whereas others cannot? In the regulation of the regeneration process as well as other biological phenomena, epigenetics plays an essential role.

Objective: This review aims to demonstrate the role of epigenetic regulators in determining regenerative capacity.

Results: In this review, we discuss the basis of regenerative differences between organisms. In addition, we present the current knowledge on the role of epigenetic regulation in regeneration, including DNA methylation, histone modification, lysine methylation, lysine methyltransferases, and the SET1 family.

Conclusion: An improved understanding of the regeneration process and the epigenetic regulation thereof through the study of regeneration in highly regenerative species will help in the field of regenerative medicine in future.

Keywords: Epigenetics, regeneration process, stem cell differentiation, histone modification, methylation of lysines, lysine methyltransferases.

[1]
Dillon SC, Zhang X, Trievel RC, Cheng X. The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol 2005; 6(8): 227.
[2]
Barkway J. Regeneration through reading. Public Library J 2007; 22: 13.
[3]
Fritz HW. Revolution and Regeneration. Libr J 1983; 108: 1480.
[4]
Sánchez Alvarado A. Planarian regeneration: its end is its beginning. Cell 2006; 124(2): 241-5.
[5]
Sánchez Alvarado A. Stem cells and the Planarian Schmidtea mediterranea. C R Biol 2007; 330(6-7): 498-503.
[6]
Reddien PW, Sánchez Alvarado A. Fundamentals of planarian regeneration. Annu Rev Cell Dev Biol 2004; 20: 725-57.
[7]
Owlarn S, Klenner F, Schmidt D, et al. Generic wound signals initiate regeneration in missing-tissue contexts. Nat Commun 2017; 8(1): 2282.
[8]
Eisenhoffer GT, Kang H, Sánchez Alvarado A. Molecular analysis of stem cells and their descendants during cell turnover and regeneration in the planarian Schmidtea mediterranea. Cell Stem Cell 2008; 3(3): 327-39.
[9]
Tanaka EM, Reddien PW. The cellular basis for animal regeneration. Dev Cell 2011; 21(1): 172-85.
[10]
Knapp D, Tanaka EM. Regeneration and reprogramming. Curr Opin Genet Dev 2012; 22(5): 485-93.
[11]
Eguizabal C, Montserrat N, Veiga A, Izpisua Belmonte JC. Dedifferentiation, transdifferentiation, and reprogramming: future directions in regenerative medicine. Semin Reprod Med 2013; 31(1): 82-94.
[12]
Kaul H, Ventikos Y. On the genealogy of tissue engineering and regenerative medicine. Tissue Eng Part B Rev 2015; 21(2): 203-17.
[13]
Ingber DE, Levin M. What lies at the interface of regenerative medicine and developmental biology? Development 2007; 134(14): 2541-7.
[14]
Sylvester KG, Longaker MT. Stem cells: review and update. Arch Surg 2004; 139(1): 93-9.
[15]
Weissman IL. Stem cells--scientific, medical, and political issues. N Engl J Med 2002; 346(20): 1576-9.
[16]
Poss KD. Advances in understanding tissue regenerative capacity and mechanisms in animals. Nat Rev Genet 2010; 11(10): 710-22.
[17]
Saló E. The power of regeneration and the stem-cell kingdom: freshwater planarians (Platyhelminthes). BioEssays 2006; 28(5): 546-59.
[18]
Falanga V. Stem cells in tissue repair and regeneration. J Invest Dermatol 2012; 132(6): 1538-41.
[19]
Chagastelles PC, Nardi NB. Biology of stem cells: an overview. Kidney Int Supp (2011) 2011; 1(3): 63-7.
[20]
Loh YH, Agarwal S, Park IH, et al. Generation of induced pluripotent stem cells from human blood. Blood 2009; 113(22): 5476-9.
[21]
Rinkevich Y, Lindau P, Ueno H, Longaker MT, Weissman IL. Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip. Nature 2011; 476(7361): 409-13.
[22]
Cai S, Fu X, Sheng Z. Dedifferentiation: A new approach in stem cell research. Bioscience 2007; 57: 655-62.
[23]
Jopling C, Boue S, Izpisua Belmonte JC. Dedifferentiation, transdifferentiation and reprogramming: Three routes to regeneration. Nat Rev Mol Cell Biol 2011; 12(2): 79-89.
[24]
Soufi A, Dalton S. Cycling through developmental decisions: how cell cycle dynamics control pluripotency, differentiation and reprogramming. Development 2016; 143(23): 4301-11.
[25]
Oliveri RS. Epigenetic dedifferentiation of somatic cells into pluripotency: cellular alchemy in the age of regenerative medicine? Regen Med 2007; 2(5): 795-816.
[26]
Xu J, Du Y, Deng H. Direct lineage reprogramming: strategies, mechanisms, and applications. Cell Stem Cell 2015; 16(2): 119-34.
[27]
Shen C-N, Horb ME, Slack JM, Tosh D. Transdifferentiation of pancreas to liver. Mech Dev 2003; 120(1): 107-16.
[28]
Ma X, Kong L, Zhu S. Reprogramming cell fates by small molecules. Protein Cell 2017; 8(5): 328-48.
[29]
Sancho-Martinez I, Ocampo A, Izpisua Belmonte JC. Reprogramming by lineage specifiers: blurring the lines between pluripotency and differentiation. Curr Opin Genet Dev 2014; 28: 57-63.
[30]
Garza-Garcia AA, Driscoll PC, Brockes JP. Evidence for the local evolution of mechanisms underlying limb regeneration in salamanders. Integr Comp Biol 2010; 50(4): 528-35.
[31]
Sánchez Alvarado A, Tsonis PA. Bridging the regeneration gap: genetic insights from diverse animal models. Nat Rev Genet 2006; 7(11): 873-84.
[32]
Holstein TW, Hobmayer E, Technau U. Cnidarians: an evolutionarily conserved model system for regeneration? Dev Dyn 2003; 226(2): 257-67.
[33]
Poss KD. Advances in understanding tissue regenerative capacity and mechanisms in animals. Nat Rev Genet 2010; 11(10): 710-22.
[34]
Birnbaum KD, Sánchez Alvarado A. Slicing across kingdoms: Regeneration in plants and animals. Cell 2008; 132(4): 697-710.
[35]
Ishida T, Nakajima T, Kudo A, Kawakami A. Phosphorylation of Junb family proteins by the Jun N-terminal kinase supports tissue regeneration in zebrafish. Dev Biol 2010; 340(2): 468-79.
[36]
Mescher AL, Neff AW. Regenerative capacity and the developing immune system. Adv Biochem Eng Biotechnol 2005; 93: 39-66.
[37]
Aurora AB, Olson EN. Immune modulation of stem cells and regeneration. Cell Stem Cell 2014; 15(1): 14-25.
[38]
Pechersky AV, Pechersky VI, Aseev MV, Droblenkov AV, Semiglazov VF. Immune system and regeneration. J Stem Cells 2016; 11(2): 69-87.
[39]
Rouhana L, Tasaki J. Epigenetics and shared Molecular Processes in the regeneration of complex structures. Stem Cells Int 2016.20166947395
[40]
Bornelöv S, Reynolds N, Xenophontos M, et al. The nucleosome remodeling and deacetylation complex modulates chromatin structure at sites of active transcription to fine-tune gene expression. Mol Cell 2018; 71(1): 56-72.e4.
[41]
Bonasio R, Tu S, Reinberg D. Molecular signals of epigenetic states. Science 2010; 330(6004): 612-6.
[42]
Woodcock CL, Dimitrov S. Higher-order structure of chromatin and chromosomes. Curr Opin Genet Dev 2001; 11(2): 130-5.
[43]
Grigoryev SA. Chromatin higher-order holding: a perspective with linker DNA angles. Biophys J 2018; 114(10): 2290-7.
[44]
Garcia-Saez I, Menoni H, Boopathi R, et al. Structure of an H1-bound 6-nucleosome array reveals an untwisted two-start chromatin fiber conformation. Mol Cell 2018; 72(5): 902-915.e7.
[45]
Eissenberg JC, Shilatifard A. Histone H3 lysine 4 (H3K4) methylation in development and differentiation. Dev Biol 2010; 339(2): 240-9.
[46]
Groth A, Rocha W, Verreault A, Almouzni G. Chromatin challenges during DNA replication and repair. Cell 2007; 128(4): 721-33.
[47]
McGhee JD, Felsenfeld G. Nucleosome structure. Annu Rev Biochem 1980; 49: 1115-56.
[48]
Richmond TJ, Davey CA. The structure of DNA in the nucleosome core. Nature 2003; 423(6936): 145-50.
[49]
Schneider R, Bannister AJ, Kouzarides T. Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem Sci 2002; 27(8): 396-402.
[50]
Pullirsch D, Härtel R, Kishimoto H, Leeb M, Steiner G, Wutz A. The Trithorax group protein Ash2l and Saf-A are recruited to the inactive X chromosome at the onset of stable X inactivation. Development 2010; 137(6): 935-43.
[51]
Cutter AR, Hayes JJ. A brief review of nucleosome structure. FEBS Lett 2015; 589(20 Pt A): 2914-22.
[52]
Qureshi IA, Mehler MF. Emerging role of epigenetics in stroke: part 1: DNA methylation and chromatin modifications. Arch Neurol 2010; 67(11): 1316-22.
[53]
Belotserkovskaya R, Oh S, Bondarenko VA, Orphanides G, Studitsky VM, Reinberg D. FACT facilitates transcription-dependent nucleosome alteration. Science 2003; 301(5636): 1090-3.
[54]
Finch JT, Lutter LC, Rhodes D, et al. Structure of nucleosome core particles of chromatin. Nature 1977; 269(5623): 29-36.
[55]
Santos-Rosa H, Caldas C. Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer 2005; 41(16): 2381-402.
[56]
Santos-Rosa H, Schneider R, Bannister AJ, et al. Active genes are tri-methylated at K4 of histone H3. Nature 2002; 419(6905): 407-11.
[57]
Ng HH, Robert F, Young RA, Struhl K. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell 2003; 11(3): 709-19.
[58]
Grewal SIS, Rice JC. Regulation of heterochromatin by histone methylation and small RNAs. Curr Opin Cell Biol 2004; 16(3): 230-8.
[59]
Cheung P, Lau P. Epigenetic regulation by histone methylation and histone variants. Mol Endocrinol 2005; 19(3): 563-73.
[60]
Santos J, Pereira CF, Di-Gregorio A, et al. Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo. Epigenetics Chromatin 2010; 3: 1.
[61]
Goldberg AD, Allis CD, Bernstein E. Epigenetics: a landscape takes shape. Cell 2007; 128(4): 635-8.
[62]
Lehner B. Genotype to phenotype: lessons from model organisms for human genetics. Nat Rev Genet 2013; 14(3): 168-78.
[63]
Biémont C. From genotype to phenotype. What do epigenetics and epigenomics tell us? Heredity 2010; 105(1): 1-3.
[64]
Costa FF. Non-coding RNAs, epigenetics and complexity. Gene 2008; 410(1): 9-17.
[65]
Vincent A, Van Seuningen I. Epigenetics, stem cells and epithelial cell fate. Differentiation 2009; 78(2-3): 99-107.
[66]
Spivakov M, Fisher AG. Epigenetic signatures of stem-cell identity. Nat Rev Genet 2007; 8(4): 263-71.
[67]
Jones PA. DNA methylation and cancer. Oncogene 2002; 21(35): 5358-60.
[68]
Lachner M, Jenuwein T. The many faces of histone lysine methylation. Curr Opin Cell Biol 2002; 14(3): 286-98.
[69]
Völkel P, Angrand PO. The control of histone lysine methylation in epigenetic regulation. Biochimie 2007; 89(1): 1-20.
[70]
Sang Y, Wu MF, Wagner D. The stem cell--chromatin connection. Semin Cell Dev Biol 2009; 20(9): 1143-8.
[71]
Bannister AJ, Kouzarides T. Reversing histone methylation. Nature 2005; 436(7054): 1103-6.
[72]
Jenuwein T, Allis CD. Translating the Histone Code Science 2001; 293(5532): 1074-80.
[73]
Sims RJ III, Nishioka K, Reinberg D. Histone lysine methylation: a signature for chromatin function. Trends Genet 2003; 19(11): 629-39.
[74]
Rose NR, Klose RJ. Understanding the relationship between DNA methylation and histone lysine methylation. Biochim Biophys Acta 2014; 1839(12): 1362-72.
[75]
Martin C, Zhang Y. The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 2005; 6(11): 838-49.
[76]
Guo L, Yu Y, Law JA, Zhang X. SET DOMAIN GROUP2 is the major histone H3 lysine [corrected] 4 trimethyltransferase in Arabidopsis. Proc Natl Acad Sci USA 2010; 107(43): 18557-62.
[77]
Dorigo B, Schalch T, Bystricky K, Richmond TJ. Chromatin fiber folding: requirement for the histone H4 N-terminal tail. J Mol Biol 2003; 327(1): 85-96.
[78]
Iwasaki W, Miya Y, Horikoshi N, et al. Contribution of histone N-terminal tails to the structure and stability of nucleosomes. FEBS Open Bio 2013; 3: 363-9.
[79]
Berr A, McCallum EJ, Ménard R, et al. Arabidopsis SET DOMAIN GROUP2 is required for H3K4 trimethylation and is crucial for both sporophyte and gametophyte development. Plant Cell 2010; 22(10): 3232-48.
[80]
Fischle W, Wang Y, Allis CD. Histone and chromatin cross-talk. Curr Opin Cell Biol 2003; 15(2): 172-83.
[81]
Trojer P, Reinberg D. Histone lysine demethylases and their impact on epigenetics. Cell 2006; 125(2): 213-7.
[82]
Terranova R, Pujol N, Fasano L, Djabali M. Characterisation of set-1, a conserved PR/SET domain gene in Caenorhabditis elegans. Gene 2002; 292(1-2): 33-41.
[83]
Miller T, Krogan NJ, Dover J, et al. COMPASS: A complex of proteins associated with a trithorax-related SET domain protein. Proc Natl Acad Sci USA 2001; 98(23): 12902-7.
[84]
Hsin JP, Manley JL. The RNA polymerase II CTD coordinates transcription and RNA processing. Genes Dev 2012; 26: 2119-37.
[85]
Hubert A, Henderson JM, Ross KG, Cowles MW, Torres J, Zayas RM. Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases. Epigenetics 2013; 8(1): 79-91.
[86]
Jin B, Li Y, Robertson KD. DNA methylation: superior or subordinate in the epigenetic hierarchy? Genes Cancer 2011; 2(6): 607-17.
[87]
Robertson KD. DNA methylation and chromatin - unraveling the tangled web. Oncogene 2002; 21(35): 5361-79.
[88]
Tate PH, Bird AP. Effects of DNA methylation on DNA-binding proteins and gene expression. Curr Opin Genet Dev 1993; 3(2): 226-31.
[89]
Górnikiewicz B, Ronowicz A, Podolak J, Madanecki P, Stanisławska-Sachadyn A, Sachadyn P. Epigenetic basis of regeneration: analysis of genomic DNA methylation profiles in the MRL/MpJ mouse. DNA Res 2013; 20(6): 605-21.
[90]
Zhu X, Xiao C, Xiong JW. Epigenetic regulation of organ regeneration in Zebrafish. J Cardiovasc Dev Dis 2018; 5(4): 57.
[91]
Aluru N, Karchner SI, Krick KS, Zhu W, Liu J. Role of DNA methylation in altered gene expression patterns in adult zebrafish (Danio rerio) exposed to 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB 126). Environl Epigenet 2018. 4: dvy005.
[92]
Javaid N, Choi S. Acetylation- and methylation-related epigenetic proteins in the context of their targets. Genes 2017; 8(8): 196.
[93]
Robb SMC, Sánchez Alvarado A. Histone modifications and regeneration in the planarian Schmidtea mediterranea. Curr Top Dev Biol 2014; 108: 71-93.
[94]
Wan J, Goldman D. Retina regeneration in zebrafish. Curr Opin Genet Dev 2016; 40: 41-7.
[95]
Mitra S, Sharma P, Kaur S, et al. Histone Deacetylase-mediated Müller glia reprogramming through Her4.1-Lin28a axis is essential for retina regeneration in zebrafish. iScience 2018; 7: 68-84.
[96]
He Y, Tang D, Li W, Chai R, Li H. Histone deacetylase 1 is required for the development of the zebrafish inner ear. Sci Rep 2016; 6: 16535.
[97]
Palmisano I, Di Giovanni S. Advances and limitations of current epigenetic studies onvestigating mammalian axonal regeneration. Neurotherapeutics 2018; 15(3): 529-40.
[98]
Wang GL, Salisbury E, Shi X, Timchenko L, Medrano EE, Timchenko NA. HDAC1 promotes liver proliferation in young mice via interactions with C/EBPbeta. J Biol Chem 2008; 283(38): 26179-87.

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    • 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=98978
      890μsalphaeurekaselec_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` = 60 limit 1
      1.18msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 60
      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=60) and sj.journal_id!=60 group by `j`.`nid`) as `aggregate_table`
      1.19msalphaeurekaselec_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=60) and sj.journal_id!=60 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.09msalphaeurekaselec_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=60) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      6.85msalphaeurekaselec_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=60) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      6.36msalphaeurekaselec_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` = '98978'
      370μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 98978
      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` = '98978'
      2.67msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 98978
      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` = '98978' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      850μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 98978
      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
      340μsalphaeurekaselec_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
      710μsalphaeurekaselec_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 = 60 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      44.45msalphaeurekaselec_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 = 60 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      16.52msalphaeurekaselec_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 = 60 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      6.5msalphaeurekaselec_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` = 98978 limit 1
      640μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 98978
      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 = 98978 and content_type = 'article' order by status desc limit 1
      260μsalphaeurekaselec_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` = 172736 limit 1
      170μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 172736
      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
      190μsalphaeurekaselec_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` = 'CSCRT' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      230μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CSCRT
      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 = '98978' 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) )
      350μsalphaeurekaselec_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 = '9340' 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) )
      260μsalphaeurekaselec_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 = '2598' 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) )
      250μsalphaeurekaselec_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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2598) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2598) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 2598)
      45.61msalphaeurekaselec_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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9340) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9340) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 9340)
      680μsalphaeurekaselec_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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 98978) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 98978) 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 <= 873368187 and j.to_ip >=873368187 )) and ((j.from_date <= 1740526982 and j.to_date >= 1740526982 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 98978)
      560μsalphaeurekaselec_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` < '598' and is_uploaded = 1 and issue_id = 9340 order by cast(first_page as SIGNED) desc limit 1
      460μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 598
      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` > '606' and is_uploaded = 1 and issue_id = 9340 order by cast(first_page as SIGNED) asc limit 1
      360μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 606
      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'
      160μsalphaeurekaselec_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
      170μsalphaeurekaselec_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` = 98978 limit 1
      2.27msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 98978
      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` = 60 and `b`.`banner_from_date` <= 1740526982 and `b`.`banner_to_date` >= 1740526982 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 60
      • 3: 1740526982
      • 4: 1740526982
      • 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` = 60 and `b`.`banner_from_date` <= 1740526982 and `b`.`banner_to_date` >= 1740526982 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.32msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 60
      • 3: 1740526982
      • 4: 1740526982
      • 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='f1d561a2d9778186b75d6cae93721a3e'
      220μsalphaeurekaselec_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#?
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        uc_cart_id
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        _flash
        array:2 [ "old" => [] "new" => [] ]
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        []
        path_info
        /article/98978
        status_code
        200
        
        status_text
        OK
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        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 23:43:02GET/article/98978314361