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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

N-acetyl Cysteine Inhibits Cell Proliferation and Differentiation of LPSInduced MC3T3-E1 Cells Via Regulating Inflammatory Cytokines

Author(s): Wangyang Li, Hui Zhang, Junchi Chen, Yujie Tan, Ailing Li and Ling Guo*

Volume 24, Issue 3, 2023

Published on: 26 August, 2022

Page: [450 - 459] Pages: 10

DOI: 10.2174/1389201023666220520102001

Price: $65

Abstract

Background: Peri-implantitis is one of the most common complications in oral implantation and could lead to the loss of the function of bone tissues around implants.

Methods: This study used lipopolysaccharide (LPS) as a stimulant for MC3T3-E1 cells and N-acetyl cysteine (NAC) as an inhibitor to inhibit the effect of LPS to investigate the effect of NAC on the expression of bone formation related factors and inflammatory-related factors of osteoblasts under the action of LPS.

Results: In this study, we found that the cell proliferation and cell differentiation were significantly promoted when NAC concentrations were between 0 ~ 0.5 mM, but were inhibited when the concentration exceeded 0.5 mM. LPS had a slightly promoting effect on the cell proliferation before 20 μg/mL but inhibited the cell proliferation after 20 μg/mL. LPS reduced protein and gene expressions of Runx2, ALP and BGP and increased protein and gene expressions of NF-κB and TNF-α. NAC reversibly regulated the LPS’s regulation on the expression of MC3T3-E1 cell cytokine gene and protein.

Conclusion: The optimal NAC concentration for treating MC3T3-E1 cells is 0.5 mM, and the optimal LPS concentration for stimulating MC3T3-E1 cells is 20 μg/mL. NAC plays an active role in regulating the differentiation of MC3T3-E1 cells, and can inhibit LPS to regulate the differentiation of MC3T3-E1 cells. NAC promotes the expression of an osteogenic factor of MC3T3-E1cells and inhibits the expression of inflammatory cytokines.

Keywords: N-acetyl cysteine, MC3T3-E1, Cytokines, lipopolysaccharide, Peri-implantitis, expression.

[1]
Yu, Y.; Qiu, L.; Guo, J.; Yang, D.; Qu, L.; Yu, J.; Zhan, F.; Xue, M.; Zhong, M. TRIB3 mediates the expression of Wnt5a and activation of nuclear factor-κB in Porphyromonas endodontalis lipopolysaccharide-treated osteoblasts. Mol. Oral Microbiol., 2015, 30(4), 295-306.
[http://dx.doi.org/10.1111/omi.12094] [PMID: 25601649]
[2]
Oh, S.L. A peri-implantitis associated with a pre-existing pathology. J. Oral Implantol., 2017, 43(3), 232-236.
[http://dx.doi.org/10.1563/aaid-joi-D-16-00211] [PMID: 28156187]
[3]
Shanbhag, S.; Pandis, N.; Mustafa, K.; Nyengaard, J.R.; Stavropoulos, A. Bone tissue engineering in oral peri-implant defects in preclinical in vivo research: A systematic review and meta-analysis. J. Tissue Eng. Regen. Med., 2018, 12(1), e336-e349.
[http://dx.doi.org/10.1002/term.2412] [PMID: 28095650]
[4]
Cosoli, G.; Scalise, L.; Tricarico, G.; Tomasini, E.P.; Cerri, G. An innovative therapy for peri-implantitis based on radio frequency electric current: Numerical simulation results and clinical evidence. Conf. Proc. IEEE Eng. Med. Biol. Soc., 2016, 2016, 5652-5655.
[http://dx.doi.org/10.1109/EMBC.2016.7592009] [PMID: 28269537]
[5]
Arab, H.; Shiezadeh, F.; Moeintaghavi, A.; Anbiaei, N.; Mohamadi, S. Comparison of two regenerative surgical treatments for peri-implantitis defect using natix alone or in combination with bio-oss and collagen membrane. J. Long Term Eff. Med. Implants, 2016, 26(3), 199-204.
[http://dx.doi.org/10.1615/JLongTermEffMedImplants.2016016396] [PMID: 28134601]
[6]
Wang, X.; Feng, Z.; Li, J.; Chen, L.; Tang, W. High glucose induces autophagy of MC3T3-E1 cells via ROS-AKT-mTOR axis. Mol. Cell. Endocrinol., 2016, 429, 62-72.
[http://dx.doi.org/10.1016/j.mce.2016.03.036] [PMID: 27068641]
[7]
Lee, D.; Kook, S.H.; Ji, H.; Lee, S.A.; Choi, K.C.; Lee, K.Y.; Lee, J.C. N-acetyl cysteine inhibits H2O2-mediated reduction in the minerali-zation of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway. BMB Rep., 2015, 48(11), 636-641.
[http://dx.doi.org/10.5483/BMBRep.2015.48.11.112] [PMID: 26303969]
[8]
Nagao, M.; Tanabe, N.; Manaka, S.; Naito, M.; Sekino, J.; Takayama, T.; Kawato, T.; Torigoe, G.; Kato, S.; Tsukune, N.; Maeno, M.; Suzuki, N.; Sato, S. LIPUS suppressed LPS-induced IL-1α through the inhibition of NF-κB nuclear translocation via AT1-PLCβ pathway in MC3T3-E1 cells. J. Cell. Physiol., 2017, 232(12), 3337-3346.
[http://dx.doi.org/10.1002/jcp.25777] [PMID: 28063227]
[9]
Gao, A.; Wang, X.; Yu, H.; Li, N.; Hou, Y.; Yu, W. Effect of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on the expression of EphA2 in osteoblasts and osteoclasts. In Vitro Cell. Dev. Biol. Anim., 2016, 52(2), 228-234.
[http://dx.doi.org/10.1007/s11626-015-9965-0] [PMID: 26559065]
[10]
Cavagis, A.; Takamori, E.; Granjeiro, J.; Oliveira, R.; Ferreira, C.; Peppelenbosch, M.; Zambuzzi, W. TNFα contributes for attenuating both Y397FAK and Y416Src phosphorylations in osteoblasts. Oral Dis., 2014, 20(8), 780-786.
[PMID: 24164869]
[11]
Sato, Y.; Ishihara, N.; Nagayama, D.; Saiki, A.; Tatsuno, I. 7-ketocholesterol induces apoptosis of MC3T3-E1 cells associated with reactive oxygen species generation, endoplasmic reticulum stress and caspase-3/7 dependent pathway. Mol. Genet. Metab. Rep., 2017, 10, 56-60.
[http://dx.doi.org/10.1016/j.ymgmr.2017.01.006] [PMID: 28116245]
[12]
Yu, Y.Q.; Qu, L.; Qiu, L.H.; Guo, J.J.; Ma, N.; Zhu, L. Mechanism of TNF-α in bone defect of chronic apical periodontitis. Shanghai Kou Qiang Yi Xue J. Stomatol., 2016, 25(4), 414-419.
[PMID: 27858062]
[13]
Liu, Y.H.; Huang, D.; Li, Z.J.; Li, X.H.; Wang, X.; Yang, H.P.; Tian, S.P.; Mao, Y.; Liu, M.F.; Wang, Y.F.; Wu, Y.; Han, X.F. Toll-like receptor-4-dependence of the lipopolysaccharidemediated inhibition of osteoblast differentiation. Genet. Mol. Res., 2016, 15(2)
[http://dx.doi.org/10.4238/gmr.15027191] [PMID: 27173231]
[14]
Liu, H.; Hao, W.; Wang, X.; Su, H. miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells. J. Toxicol. Sci., 2016, 41(2), 185-193.
[http://dx.doi.org/10.2131/jts.41.185] [PMID: 26961602]
[15]
Choudhury, S.; Ghosh, S.; Gupta, P.; Mukherjee, S.; Chattopadhyay, S. Inflammation-induced ROS generation causes pancreatic cell death through modulation of Nrf2/NF-κB and SAPK/JNK pathway. Free Radic. Res., 2015, 49(11), 1371-1383.
[http://dx.doi.org/10.3109/10715762.2015.1075016] [PMID: 26189548]
[16]
Nam, Y.J.; Lee, D.H.; Lee, M.S.; Lee, C.S. Sesquiterpene lactone parthenolide attenuates production of inflammatory mediators by suppressing the Toll-like receptor-4-mediated activation of the Akt, mTOR, and NF-κB pathways. Naunyn Schmiedebergs Arch. Pharmacol., 2015, 388(9), 921-930.
[http://dx.doi.org/10.1007/s00210-015-1132-3] [PMID: 25971793]
[17]
Hou, Y.; Wang, L.; Yi, D.; Wu, G. N-acetylcysteine and intestinal health: A focus on its mechanism of action. Front. Biosci., 2015, 20(5), 872-891.
[http://dx.doi.org/10.2741/4342] [PMID: 25553484]
[18]
Wang, Y.N.; Jia, T.T.; Feng, Y.; Liu, S.Y.; Zhang, W.J.; Zhang, D.J.; Xu, X. Hyperlipidemia impairs osseointegration via the ROS/Wnt/β-catenin pathway. J. Dent. Res., 2021, 100(6), 658-665.
[http://dx.doi.org/10.1177/0022034520983245] [PMID: 33402029]
[19]
Mostofi, S.; Bonyadi Rad, E.; Wiltsche, H.; Fasching, U.; Szakacs, G.; Ramskogler, C.; Srinivasaiah, S.; Ueçal, M.; Willumeit, R.; Weinberg, A.M.; Schaefer, U. Effects of corroded and noncorroded biodegradable Mg and Mg alloys on viability, morphology and differentiation of MC3T3-E1 cells elicited by direct cell/material interaction. PLoS One, 2016, 11(7), e0159879.
[http://dx.doi.org/10.1371/journal.pone.0159879] [PMID: 27459513]
[20]
Hendesi, H.; Barbe, M.F.; Safadi, F.F.; Monroy, M.A.; Popoff, S.N. Integrin mediated adhesion of osteoblasts to connective tissue growth factor (CTGF/CCN2) induces cytoskeleton reorganization and cell differentiation. PLoS One, 2015, 10(2), e0115325.
[http://dx.doi.org/10.1371/journal.pone.0115325] [PMID: 25714841]
[21]
Valente, N.A.; Mang, T.; Hatton, M.; Mikulski, L.; Andreana, S. Effects of two diode lasers with and without photosensitization on contaminated implant surfaces: An ex vivo study. Photomed. Laser Surg., 2017, 35(7), 347-356.
[http://dx.doi.org/10.1089/pho.2016.4247] [PMID: 28253064]
[22]
Rathnayake, N.; Gieselmann, D.R.; Heikkinen, A.M.; Tervahartiala, T.; Sorsa, T. Salivary diagnostics-point-of-care diagnostics of MMP-8 in dentistry and medicine. Diagnostics (Basel), 2017, 7(1), 7.
[http://dx.doi.org/10.3390/diagnostics7010007] [PMID: 28117682]
[23]
Karimi, M.R.; Hasani, A.; Khosroshahian, S. Efficacy of antimicrobial photodynamic therapy as an adjunctive to mechanical debridement in the treatment of peri-implant diseases: A randomized controlled clinical trial. J. Lasers Med. Sci., 2016, 7(3), 139-145.
[http://dx.doi.org/10.15171/jlms.2016.24] [PMID: 28144432]
[24]
Yang, L.; Meng, H.; Yang, M. Autophagy protects osteoblasts from advanced glycation end products-induced apoptosis through intracellular reactive oxygen species. J. Mol. Endocrinol., 2016, 56(4), 291-300.
[http://dx.doi.org/10.1530/JME-15-0267] [PMID: 26903511]
[25]
Arakaki, N.; Yamashita, A.; Niimi, S.; Yamazaki, T. Involvement of reactive oxygen species in osteoblastic differentiation of MC3T3-E1 cells accompanied by mitochondrial morphological dynamics. Biomed. Res., 2013, 34(3), 161-166.
[http://dx.doi.org/10.2220/biomedres.34.161] [PMID: 23782750]
[26]
Meresta, A.; Folkert, J.; Gaber, T.; Miksch, K.; Buttgereit, F.; Detert, J.; Pischon, N.; Gurzawska, K. Plant-derived pectin nanocoatings to prevent inflammatory cellular response of osteoblasts following Porphyromonas gingivalis infection. Int. J. Nanomedicine, 2017, 12, 433-445.
[http://dx.doi.org/10.2147/IJN.S113740] [PMID: 28138240]
[27]
Folkert, J.; Meresta, A.; Gaber, T.; Miksch, K.; Buttgereit, F.; Detert, J.; Pischon, N.; Gurzawska, K. Nanocoating with plant-derived pectins activates osteoblast response in vitro. Int. J. Nanomedicine, 2016, 12, 239-249.
[http://dx.doi.org/10.2147/IJN.S99020] [PMID: 28096669]
[28]
Haneji, T. Roles of PKR in differentiation and apoptosis of bonerelated cells. Anat. Sci. Int., 2017, 92(3), 313-319.
[http://dx.doi.org/10.1007/s12565-016-0385-3] [PMID: 27987116]
[29]
Postema, M.; Gilja, O.H. Ultrasound-directed drug delivery. Curr. Pharm. Biotechnol., 2007, 8(6), 355-361.
[http://dx.doi.org/10.2174/138920107783018453] [PMID: 18289044]
[30]
Park, S.Y.; Kim, S.H.; Yoon, H.K.; Yim, C.H.; Lim, S.K. The role of nuclear factor-E2-related factor 1 in the oxidative stress response in MC3T3-E1 osteoblastic cells. Endocrinol. Metab. (Seoul), 2016, 31(2), 336-342.
[http://dx.doi.org/10.3803/EnM.2016.31.2.336] [PMID: 27118276]
[31]
Wang, J.; Wu, G.; Liu, X.; Sun, G.; Li, D.; Wei, H. A decomposable silica-based antibacterial coating for percutaneous titanium implant. Int. J. Nanomedicine, 2017, 12, 371-379.
[http://dx.doi.org/10.2147/IJN.S123622] [PMID: 28123297]
[32]
Ziebolz, D.; Schmalz, G.; Gollasch, D.; Eickholz, P.; Rinke, S. Microbiological and aMMP-8 findings depending on peri-implant disease in patients undergoing supportive implant therapy. Diagn. Microbiol. Infect. Dis., 2017, 88(1), 47-52.
[http://dx.doi.org/10.1016/j.diagmicrobio.2017.02.008] [PMID: 28274501]
[33]
Govindharajulu, J.P.; Chen, X.; Li, Y.; Rodriguez-Cabello, J.C.; Battacharya, M.; Aparicio, C. Chitosan-recombinamer layer-bylayer coatings for multifunctional implants. Int. J. Mol. Sci., 2017, 18(2), 369.
[http://dx.doi.org/10.3390/ijms18020369] [PMID: 28208793]
[34]
Mohamadyar-Toupkanlou, F.; Vasheghani-Farahani, E.; Hanaee-Ahvaz, H.; Soleimani, M.; Dodel, M.; Havasi, P.; Ardeshirylajimi, A.; Taherzadeh, E.S. Osteogenic differentiation of MSCs on fibronectin coated and nHA-modified scaffolds. ASAIO J., 2017, 63(5), 684-691.
[http://dx.doi.org/10.1097/MAT.0000000000000551] [PMID: 28234642]
[35]
You, M.; Li, K.; Xie, Y.; Huang, L.; Zheng, X. The effects of cerium valence states at cerium oxide coatings on the responses of bone mesenchymal stem cells and macrophages. Biol. Trace Elem. Res., 2017, 179(2), 259-270.
[http://dx.doi.org/10.1007/s12011-017-0968-4] [PMID: 28229387]
[36]
Xie, Q.; Wei, W.; Ruan, J.; Ding, Y.; Zhuang, A.; Bi, X.; Sun, H.; Gu, P.; Wang, Z.; Fan, X. Effects of miR-146a on the osteogenesis of adipose-derived mesenchymal stem cells and bone regeneration. Sci. Rep., 2017, 7(1), 42840.
[http://dx.doi.org/10.1038/srep42840] [PMID: 28205638]
[37]
Sumegi, K.; Fekete, K.; Antus, C.; Debreceni, B.; Hocsak, E.; Gallyas, F., Jr; Sumegi, B.; Szabo, A. BGP-15 protects against oxidative stress- or lipopolysaccharide-induced mitochondrial destabilization and reduces mitochondrial production of reactive oxygen species. PLoS One, 2017, 12(1), e0169372.
[http://dx.doi.org/10.1371/journal.pone.0169372] [PMID: 28046125]
[38]
Bin, G.; Bo, Z.; Jing, W.; Jin, J.; Xiaoyi, T.; Cong, C.; Liping, A.; Jinglin, M.; Cuifang, W.; Yonggang, C.; Yayi, X. Fluid shear stress suppresses TNF-α-induced apoptosis in MC3T3-E1 cells: Involvement of ERK5-AKT-FoxO3a-Bim/FasL signaling pathways. Exp. Cell Res., 2016, 343(2), 208-217.
[http://dx.doi.org/10.1016/j.yexcr.2016.03.014] [PMID: 27060196]
[39]
Koyama, T.; Kamemura, K. Global increase in O-linked N-acetylglucosamine modification promotes osteoblast differentiation. Exp. Cell Res., 2015, 338(2), 194-202.
[http://dx.doi.org/10.1016/j.yexcr.2015.08.009] [PMID: 26302267]
[40]
Ma, S.; Imazato, S.; Takahashi, Y.; Kiba, W.; Takeda, K.; Izutani, N.; Kitagawa, H.; Chen, J. Mechanism of detoxification of the cationic antibacterial monomer 12-methacryloyloxydodecylpyridiniumbromide (MDPB) by N-acetyl cysteine. Dent. Mater., 2013, 29(12), 1219-1227.
[http://dx.doi.org/10.1016/j.dental.2013.09.008] [PMID: 24119918]
[41]
Lee, D.H.; Lim, B.S.; Lee, Y.K.; Yang, H.C. Mechanisms of root canal sealers cytotoxicity on osteoblastic cell line MC3T3-E1. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod., 2007, 104(5), 717-721.
[http://dx.doi.org/10.1016/j.tripleo.2007.05.018] [PMID: 17706441]

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      • 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=123802
      2.78msalphaeurekaselec_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` = 30 limit 1
      4.16msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 30
      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=30) and sj.journal_id!=30 group by `j`.`nid`) as `aggregate_table`
      1.91msalphaeurekaselec_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=30) and sj.journal_id!=30 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.52msalphaeurekaselec_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=30) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.78msalphaeurekaselec_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=30) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      5.47msalphaeurekaselec_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` = '123802'
      1.6msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 123802
      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` = '123802'
      4.87msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 123802
      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` = '123802' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      3.31msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 123802
      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
      370μsalphaeurekaselec_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
      750μsalphaeurekaselec_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 = 30 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      73.43msalphaeurekaselec_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 = 30 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      39.48msalphaeurekaselec_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 = 30 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      21.53msalphaeurekaselec_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` = 123802 limit 1
      1.99msalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 123802
      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 = 123802 and content_type = 'article' order by status desc limit 1
      350μsalphaeurekaselec_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` = 205059 limit 1
      270μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 205059
      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
      320μsalphaeurekaselec_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` = 'CPB' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      430μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CPB
      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 = '123802' 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) )
      550μsalphaeurekaselec_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 = '12216' 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) )
      440μsalphaeurekaselec_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 = '3326' 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) )
      420μsalphaeurekaselec_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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3326) 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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3326) 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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3326)
      124msalphaeurekaselec_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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12216) 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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12216) 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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12216)
      980μsalphaeurekaselec_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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 123802) 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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 123802) 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 <= 221975353 and j.to_ip >=221975353 )) and ((j.from_date <= 1740775942 and j.to_date >= 1740775942 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 123802)
      1.37msalphaeurekaselec_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` < '450' and is_uploaded = 1 and issue_id = 12216 order by cast(first_page as SIGNED) desc limit 1
      960μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 450
      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` > '459' and is_uploaded = 1 and issue_id = 12216 order by cast(first_page as SIGNED) asc limit 1
      860μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 459
      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'
      270μsalphaeurekaselec_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
      310μsalphaeurekaselec_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` = 123802 limit 1
      4.55msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 123802
      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` = 30 and `b`.`banner_from_date` <= 1740775942 and `b`.`banner_to_date` >= 1740775942 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.73msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 30
      • 3: 1740775942
      • 4: 1740775942
      • 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` = 30 and `b`.`banner_from_date` <= 1740775942 and `b`.`banner_to_date` >= 1740775942 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.94msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 30
      • 3: 1740775942
      • 4: 1740775942
      • 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='c22a120285e07ae8a2c83bb611e39652'
      370μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:291
      • 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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        dL1ylM2kzSL1nytEel66s79sHWWHS9geJv3vBadE
        uc_cart_id
        c22a120285e07ae8a2c83bb611e39652
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        array:1 [ "url" => "http://alpha.eurekaselect.com/article/123802" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
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        status_code
        200
        
        status_text
        OK
        format
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        text/html; charset=UTF-8
        request_query
        []
        
        request_request
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        request_headers
        0 of 0
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        request_cookies
        []
        
        response_headers
        0 of 0
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        array:5 [ "_token" => "dL1ylM2kzSL1nytEel66s79sHWWHS9geJv3vBadE" "uc_cart_id" => "c22a120285e07ae8a2c83bb611e39652" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/123802" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-28 20:52:22GET/article/123802514361