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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Formulation and Characterization of Phytosomes as Drug Delivery System of Formononetin: An Effective Anti-Osteoporotic Agent

Author(s): Arun Agarwal, Muhammad Wahajuddin*, Swati Chaturvedi, Sandeep K. Singh, Mamunur Rashid, Richa Garg, DIvya Chauhan, Nazneen Sultana and Jiaur R. Gayen

Volume 21, Issue 2, 2024

Published on: 08 February, 2023

Page: [261 - 270] Pages: 10

DOI: 10.2174/1567201820666230124114906

Price: $65

Abstract

Background: Formononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II classification.

Objective: We designed the present work to enhance FNT oral bioavailability by using Phospholipids (PL) as a promising carrier. Formononetin Phospholipid Complex (FNT-PC) was prepared by the solvent evaporation method and characterized.

Methods: FNT-PC was prepared by solvent evaporation method and characterization (FNT-PC) was performed using aqueous/n-octanol solubility and partition coefficient, FTIR, NMR, SEM, and in vivo pharmacokinetic study in female SD rats at 50 mg/kg.

Results: Physicochemical properties like aqueous/n-octanol solubility and partition coefficient were enhanced in FNT-PC. The FTIR spectrum confirmed there was no involvement of functional groups in the preparation of FNT-PC. Whereas, the NMR study resulted in the attachment of carbon (C-8) position of FNT by replacing the quaternary amine of PL to form FNT-PC. When scrutinized for its surface morphology, the FNT-PC exhibited the amorphous geometry that remarkably enhanced the dissolution of FNT (p<0.05) from its pure form. This dissolution effect was also affirmed by the per-oral administration of FNT-PC in female Sprague Dawley (SD) rats at 50 mg/kg dose. The pharmacokinetic profile showed the free FNT levels were markedly increased, correspondingly decreasing the conjugated FNT levels in rat plasma.

Conclusion: To summarize, FNT-PC could substantially reduce the first-pass metabolism with enhanced free concentration, improving oral bioavailability for therapeutic use.

Graphical Abstract

[1]
Nie, T.; Zhao, S.; Mao, L.; Yang, Y.; Sun, W.; Lin, X.; Liu, S.; Li, K.; Sun, Y.; Li, P.; Zhou, Z.; Lin, S.; Hui, X.; Xu, A.; Ma, C.W.; Xu, Y.; Wang, C.; Dunbar, P.R.; Wu, D. The natural compound, formononetin, extracted from Astragalus membranaceus increases adipocyte thermogenesis by modulating PPARγ activity. Br. J. Pharmacol., 2018, 175(9), 1439-1450.
[http://dx.doi.org/10.1111/bph.14139] [PMID: 29315511]
[2]
Clifton-Bligh, P.B.; Nery, M-L.; Clifton-Bligh, R.J.; Visvalingam, S.; Fulcher, G.R.; Byth, K.; Baber, R. Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized, double-blind, placebo-controlled study. Eur. J. Clin. Nutr., 2015, 69(1), 134-142.
[http://dx.doi.org/10.1038/ejcn.2014.207] [PMID: 25369831]
[3]
Zhou, R.; Xu, L.; Ye, M.; Liao, M.; Du, H.; Chen, H. Formononetin inhibits migration and invasion of MDA-MB-231 and 4T1 breast cancer cells by suppressing MMP-2 and MMP-9 through PI3K/AKT signaling pathways. Horm. Metab. Res., 2014, 46(11), 753-760.
[http://dx.doi.org/10.1055/s-0034-1376977] [PMID: 24977660]
[4]
Wu, Y.; Zhang, X.; Li, Z.; Yan, H.; Qin, J.; Li, T. Formononetin inhibits human bladder cancer cell proliferation and invasiveness via regulation of miR-21 and PTEN. Food Funct., 2017, 8(3), 1061-1066.
[http://dx.doi.org/10.1039/C6FO01535B] [PMID: 28139790]
[5]
Yang, Y.; Zhao, Y.; Ai, X.; Cheng, B.; Lu, S. Formononetin suppresses the proliferation of human non-small cell lung cancer through induction of cell cycle arrest and apoptosis. Int. J. Clin. Exp. Pathol., 2014, 7(12), 8453-8461.
[PMID: 25674209]
[6]
Auyeung, K.K.W.; Law, P.C.; Ko, J.K.S. Novel anti-angiogenic effects of formononetin in human colon cancer cells and tumor xenograft. Oncol. Rep., 2012, 28(6), 2188-2194.
[http://dx.doi.org/10.3892/or.2012.2056] [PMID: 23023137]
[7]
Singh, S.P. Wahajuddin; Tewari, D.; Pradhan, T.; Jain, G.K. PAMPA permeability, plasma protein binding, blood partition, pharmacokinetics and metabolism of formononetin, a methoxylated isoflavone. Food Chem. Toxicol., 2011, 49(5), 1056-1062.
[http://dx.doi.org/10.1016/j.fct.2011.01.012] [PMID: 21266188]
[8]
Wang, D.S.; Yan, L.Y.; Yang, D.Z.; Lyu, Y.; Fang, L.H.; Wang, S.B.; Du, G.H. Formononetin ameliorates myocardial ischemia/reperfusion injury in rats by suppressing the ROS-TXNIP-NLRP3 pathway. Biochem. Biophys. Res. Commun., 2020, 525(3), 759-766.
[http://dx.doi.org/10.1016/j.bbrc.2020.02.147] [PMID: 32145915]
[9]
Wang, G.; Liu, H.; Liu, Y.; Li, H.; Li, Z.; Shao, G.; Lv, X. Formononetin alleviates Streptococcus suis infection by targeting suilysin. Microb. Pathog., 2020, 147, 104388.
[http://dx.doi.org/10.1016/j.micpath.2020.104388] [PMID: 32687939]
[10]
Yi, L.; Lu, Y.; Yu, S.; Cheng, Q.; Yi, L. Formononetin inhibits inflammation and promotes gastric mucosal angiogenesis in gastric ulcer rats through regulating NF-κB signaling pathway. J. Recept. Signal Transduc., 2020, 42(1), 16-22.
[http://dx.doi.org/10.1080/10799893.2020.1837873] [PMID: 33100111]
[11]
Yuan, W.Y.; Li, L.Q.; Chen, Y.Y.; Zhou, Y.J.; Bao, K.F.; Zheng, J.; Hua, Y.Q.; Jiang, G.R.; Hong, M. Frontline Science: Two flavonoid compounds attenuate allergic asthma by regulating epithelial barrier via G protein‐coupled estrogen receptor: Probing a possible target for allergic inflammation. J. Leukoc. Biol., 2020, 108(1), 59-71.
[http://dx.doi.org/10.1002/JLB.3HI0220-342RR] [PMID: 32303124]
[12]
Yi, L.; Cui, J.; Wang, W.; Tang, W.; Teng, F.; Zhu, X.; Qin, J.; Wuniqiemu, T.; Sun, J.; Wei, Y.; Dong, J. Formononetin attenuates airway inflammation and oxidative stress in murine allergic asthma. Front. Pharmacol., 2020, 11, 533841.
[http://dx.doi.org/10.3389/fphar.2020.533841] [PMID: 33013383]
[13]
Zhang, Y.; Chen, C.; Zhang, J. Effects and significance of formononetin on expression levels of HIF 1α and VEGF in mouse cervical cancer tissue. Oncol. Lett., 2019, 18(3), 2248-2253.
[http://dx.doi.org/10.3892/ol.2019.10567] [PMID: 31452725]
[14]
Chaturvedi, S.; Azmi, L.; Shukla, I.; Naseem, Z.; Rao, C.V. Agarwal, NKJPM Gastroprotective effect of formononetin against ethanol-induced gastric ulceration in rats via augmentation of cytoprotective markers and curtailing apoptotic gene expression. Pharmacogn., 2018, 14(59), 605-612.
[15]
Jia, X.; Chen, J.; Lin, H.; Hu, M. Disposition of flavonoids viaenteric recycling: Enzyme-transporter coupling affects metabolism of biochanin A and formononetin and excretion of their phase II conjugates. J. Pharmacol. Exp. Ther., 2004, 310(3), 1103-1113.
[http://dx.doi.org/10.1124/jpet.104.068403] [PMID: 15128864]
[16]
Wu, B.; Kulkarni, K.; Basu, S.; Zhang, S.; Hu, M. First-pass metabolism viaUDP-glucuronosyltransferase: A barrier to oral bioavailability of phenolics. J. Pharm. Sci., 2011, 100(9), 3655-3681.
[http://dx.doi.org/10.1002/jps.22568] [PMID: 21484808]
[17]
Luo, L.Y.; Fan, M.X.; Zhao, H.Y.; Li, M.X.; Wu, X.; Gao, W.Y. Pharmacokinetics and bioavailability of the isoflavones formononetin and ononin and their in vitro absorption in ussing chamber and Caco-2 cell models. J. Agric. Food Chem., 2018, 66(11), 2917-2924.
[http://dx.doi.org/10.1021/acs.jafc.8b00035] [PMID: 29504397]
[18]
Chen, L.; Choi, J.; Leonard, S.W.; Banuvar, S.; Barengolts, E.; Viana, M.; Chen, S.N.; Pauli, G.F.; Bolton, J.L.; van Breemen, R.B. No clinically relevant pharmacokinetic interactions of a red clover dietary supplement with cytochrome p450 enzymes in women. J. Agric. Food Chem., 2020, 68(47), 13929-13939.
[http://dx.doi.org/10.1021/acs.jafc.0c05856] [PMID: 33197178]
[19]
Guo, B.; Xu, D.; Liu, X.; Liao, C.; Li, S.; Huang, Z.; Li, X.; Yi, J. Characterization and cytotoxicity of PLGA nanoparticles loaded with formononetin cyclodextrin complex. J. Drug Deliv. Sci. Technol., 2017, 41, 375-383.
[http://dx.doi.org/10.1016/j.jddst.2017.08.010]
[20]
Liu, X.; Xu, D.; Liao, C.; Fang, Y.; Guo, B. Development of a promising drug delivery for formononetin: Cyclodextrin-modified single-walled carbon nanotubes. J. Drug Deliv. Sci. Technol., 2018, 43, 461-468.
[http://dx.doi.org/10.1016/j.jddst.2017.11.018]
[21]
Urandur, S.; Banala, V.T.; Shukla, R.P.; Mittapelly, N.; Pandey, G.; Kalleti, N.; Mitra, K.; Rath, S.K.; Trivedi, R.; Ramarao, P.; Mishra, P.R. Anisamide-anchored lyotropic nano-liquid crystalline particles with AIE effect: A smart optical beacon for tumor imaging and therapy. ACS Appl. Mater. Interfaces, 2018, 10(15), 12960-12974.
[http://dx.doi.org/10.1021/acsami.7b19109] [PMID: 29577719]
[22]
Dias, P.H.; Scopel, M.; Martiny, S.; Bianchi, S.E.; Bassani, V.L.; Zuanazzi, J.A.S. Hydroxypropyl-β-cyclodextrin-containing hydrogel enhances skin formononetin permeation/retention. J. Pharm. Pharmacol., 2018, 70(7), 865-873.
[http://dx.doi.org/10.1111/jphp.12915] [PMID: 29635682]
[23]
Rao, T.; Gong, Y.F.; Peng, J.B.; Wang, Y.C.; He, K.; Zhou, H.H.; Tan, Z.R.; Lv, L.Z. Comparative pharmacokinetic study on three formulations of Astragali radix by an LC–MS/MS method for determination of formononetin in human plasma. Biomed. Chromatogr., 2019, 33(9), e4563.
[http://dx.doi.org/10.1002/bmc.4563] [PMID: 31025385]
[24]
Peter, V.H. Review–an update on the use of oral phospholipid excipients. Eur. J. Pharm. Sci., 2017, 108, 1-12.
[http://dx.doi.org/10.1016/j.ejps.2017.07.008] [PMID: 28711714]
[25]
Kuche, K.; Bhargavi, N.; Dora, C.P.; Jain, S. Drug-phospholipid complex—A go through strategy for enhanced oral bioavailability. AAPS PharmSciTech, 2019, 20(2), 43.
[http://dx.doi.org/10.1208/s12249-018-1252-4] [PMID: 30610392]
[26]
Alhakamy, N.A.A.; Fahmy, U.; Badr-Eldin, S.M.; Ahmed, O.A.; Asfour, H.Z.; Aldawsari, H.M. Optimized icariin phytosomes exhibit enhanced cytotoxicity and apoptosis-inducing activities in ovarian cancer cells. Pharmaceutics, 2020, 12(4), 346.
[http://dx.doi.org/10.3390/pharmaceutics12040346] [PMID: 32290412]
[27]
Maiti, K.; Mukherjee, K.; Gantait, A.; Ahamed, H.N.; Mukherjee, P. Enhanced therapeutic benefit of quercetin–phospholipid complex in carbon tetrachloride–induced acute liver injury in rats: A comparative study. IJPT, 2005, 4, 84-90. http://dx.doi.org/1735-2657/05/42-84-90
[28]
Zhang, Y.; Huo, M.; Zhou, J. PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Comput. Methods Programs Biomed., 2010, 99(3), 306-314.
[http://dx.doi.org/10.1016/j.cmpb.2010.01.007] [PMID: 20176408]
[29]
Mazumder, A.; Dwivedi, A.; du Preez, J.L.; du Plessis, J. In vitro wound healing and cytotoxic effects of sinigrin–phytosome complex. Int. J. Pharm., 2016, 498(1-2), 283-293.
[http://dx.doi.org/10.1016/j.ijpharm.2015.12.027] [PMID: 26706438]
[30]
Wang, H.; Cui, Y.; Fu, Q.; Deng, B.; Li, G.; Yang, J. A phospholipid complex to improve the oral bioavailability of flavonoids. Drug Dev. Ind. Pharm., 2015, 41(10), 1693-1703.
[http://dx.doi.org/10.3109/03639045.2014.991402] [PMID: 25496311]
[31]
Jermain, S.V.; Brough, C.; Williams, R.O. III Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery – An update. Int. J. Pharm., 2018, 535(1-2), 379-392.
[http://dx.doi.org/10.1016/j.ijpharm.2017.10.051] [PMID: 29128423]
[32]
Tan, Q.; Liu, S.; Chen, X.; Wu, M.; Wang, H.; Yin, H.; He, D.; Xiong, H.; Zhang, J. Design and evaluation of a novel evodiamine-phospholipid complex for improved oral bioavailability. AAPS PharmSciTech, 2012, 13(2), 534-547.
[http://dx.doi.org/10.1208/s12249-012-9772-9] [PMID: 22454136]
[33]
Singh, C.; Bhatt, T.D.; Gill, M.S.; Suresh, S. Novel rifampicin–phospholipid complex for tubercular therapy: Synthesis, physicochemical characterization and in vivo evaluation. Int. J. Pharm., 2014, 460(1-2), 220-227.
[http://dx.doi.org/10.1016/j.ijpharm.2013.10.043] [PMID: 24188983]

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      • 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=18) and sj.journal_id!=18 group by `j`.`nid`) as `aggregate_table`
      990μsalphaeurekaselec_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=18) and sj.journal_id!=18 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      810μsalphaeurekaselec_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=18) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.67msalphaeurekaselec_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=18) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.53msalphaeurekaselec_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` = '129050'
      180μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 129050
      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` = '129050'
      2.81msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 129050
      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` = '129050' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      850μsalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 129050
      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
      210μsalphaeurekaselec_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
      420μsalphaeurekaselec_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 = 18 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      25.34msalphaeurekaselec_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 = 18 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      11.3msalphaeurekaselec_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 = 18 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      8.82msalphaeurekaselec_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` = 129050 limit 1
      160μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 129050
      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 = 129050 and content_type = 'article' order by status desc limit 1
      220μsalphaeurekaselec_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` = 213087 limit 1
      190μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 213087
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      200μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'CDD' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      310μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CDD
      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 = '129050' 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) )
      340μsalphaeurekaselec_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 = '12719' 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) )
      310μsalphaeurekaselec_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 = '3438' 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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3438) 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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3438) 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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3438)
      2.43msalphaeurekaselec_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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12719) 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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12719) 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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 12719)
      520μsalphaeurekaselec_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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 129050) 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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 129050) 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 <= 59274385 and j.to_ip >=59274385 )) and ((j.from_date <= 1739834512 and j.to_date >= 1739834512 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 129050)
      520μsalphaeurekaselec_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` < '261' and is_uploaded = 1 and issue_id = 12719 order by cast(first_page as SIGNED) desc limit 1
      450μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 261
      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` > '270' and is_uploaded = 1 and issue_id = 12719 order by cast(first_page as SIGNED) asc limit 1
      390μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 270
      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` = 129050 limit 1
      2.35msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 129050
      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` = 18 and `b`.`banner_from_date` <= 1739834513 and `b`.`banner_to_date` >= 1739834513 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.09msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 18
      • 3: 1739834513
      • 4: 1739834513
      • 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` = 18 and `b`.`banner_from_date` <= 1739834513 and `b`.`banner_to_date` >= 1739834513 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.03msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 18
      • 3: 1739834513
      • 4: 1739834513
      • 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='8d96d86428cdea824af7ae41675d613e'
      200μsalphaeurekaselec_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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        sMFnBIswVLyVNU8gwxFKcZpP7BRZAD19n2qkHXZJ
        uc_cart_id
        8d96d86428cdea824af7ae41675d613e
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        array:1 [ "url" => "https://alpha.eurekaselect.com/article/129050" ]
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        PHPDEBUGBAR_STACK_DATA
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        status_code
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        status_text
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        format
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        request_query
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        request_request
        []
        
        request_headers
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        request_cookies
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        response_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:21:53GET/article/129050414361