Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

In silico Investigation of Identified Major Metabolites from Coffea Arabica Leaves against Parkinson’s Disease Target Proteins for Neuroprotective Drug Development

Author(s): Christine Joyce Rejano, Lemmuel Tayo, Bor-Yann Chen and Po-Wei Tsai*

Volume 21, Issue 14, 2024

Published on: 16 October, 2023

Page: [3030 - 3038] Pages: 9

DOI: 10.2174/0115701808268540231011071359

Price: $65

Abstract

Introduction: Parkinson’s disease (PD) is a prevalent neurological disease characterized by the gradual degeneration of dopaminergic neurons leading to a dysfunctional central nervous system. Recently, major metabolites of Coffea arabica leaves were revealed to exhibit good electronshuttling potential in Microbial Fuel Cells (MFCs), similar to neurotransmitters dopamine and epinephrine.

Objective: This In silico study aimed to identify the neuroprotective potentials of plant metabolites from coffee leaves and to determine their physicochemical and pharmacokinetic properties for developing viable anti-parkinsonian drug design.

Methodology: Molecular docking was performed to evaluate the affinity of identified major compounds in C. arabica against PD-target proteins and compare the results with the binding activity of existing drugs and natural ligands of the identified protein targets via LibDock scores. The druglikeness and ADMET profiles of each ligand were also evaluated using bioinformatics tools.

Results: C. arabica metabolites exhibited various degrees of binding activity against PD targets. LibDock scores of test compounds showed that catechin, mangiferin, and chlorogenic acid exhibited higher docking scores than dopamine and levodopa. Physicochemical and pharmacokinetics analysis of the selected molecules revealed caffeine, catechin, and chlorogenic acid as promising candidates for drug development with a low risk of drug toxicity.

Conclusion: The present study indicates that Coffea arabica leaves contain promising neuroprotective active compounds against Parkinson’s disease.

[1]
Kalia, L.V.; Lang, A.E. Parkinson’s disease. Lancet, 2015, 386(9996), 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID: 25904081]
[2]
Dong-Chen, X.; Yong, C.; Yang, X.; Chen-Yu, S.; Li-Hua, P. Signaling pathways in Parkinson’s disease: Molecular mechanisms and therapeutic interventions. Signal Transduct. Target. Ther., 2023, 8(1), 73.
[http://dx.doi.org/10.1038/s41392-023-01353-3] [PMID: 36810524]
[3]
Kouli, A.; Torsney, K.M.; Kuan, W.L. Parkinson’s Disease: Etiology, neuropathology, and pathogenesis. In: Parkinson’s Disease: Pathogenesis and Clinical Aspects; Codon Publications, 2018; pp. 3-26.
[http://dx.doi.org/10.15586/codonpublications.parkinsonsdisease.2018.ch1]
[4]
Gandhi, K.R.; Saadabadi, A. Levodopa (L-Dopa); StatPearls, 2023.
[5]
Zahoor, I.; Shafi, A.; Haq, E. Pharmacological Treatment of Parkinson’s Disease. In: Parkinson’s Disease: Pathogenesis and Clinical Aspects; Codon Publications: Brisbane (AU), 2018.
[http://dx.doi.org/10.15586/codonpublications.parkinsonsdisease.2018.ch7]
[6]
Jagadeesan, A.J.; Murugesan, R.; Vimala Devi, S.; Meera, M.; Madhumala, G.; Vishwanathan Padmaja, M.; Ramesh, A.; Banerjee, A.; Sushmitha, S.; Khokhlov, A.N.; Marotta, F.; Pathak, S. Current trends in etiology, prognosis and therapeutic aspects of Parkinson’s disease: A review. Acta Biomed., 2017, 88(3), 249-262.
[PMID: 29083328]
[7]
Diaz, N.L.; Waters, C.H. Current strategies in the treatment of Parkinson’s disease and a personalized approach to management. Expert Rev. Neurother., 2009, 9(12), 1781-1789.
[http://dx.doi.org/10.1586/ern.09.117] [PMID: 19951137]
[8]
Rahman, M.H.; Bajgai, J.; Fadriquela, A.; Sharma, S.; Trinh, T.T.; Akter, R.; Jeong, Y.J.; Goh, S.H.; Kim, C.S.; Lee, K.J. Therapeutic potential of natural products in treating neurodegenerative disorders and their future prospects and challenges. Molecules, 2021, 26(17), 5327.
[http://dx.doi.org/10.3390/molecules26175327] [PMID: 34500759]
[9]
Maher, P. The potential of flavonoids for the treatment of neurodegenerative diseases. Int. J. Mol. Sci., 2019, 20(12), 3056.
[http://dx.doi.org/10.3390/ijms20123056] [PMID: 31234550]
[10]
Tsai, P.W.; Mailem, R.C.; Tayo, L.L.; Hsueh, C.C.; Tseng, C.C.; Chen, B.Y. Interactive network pharmacology and electrochemical analysis reveals electron transport-mediating characteristics of Chinese medicine formula Jing Guan Fang. J. Taiwan Inst. Chem. Eng., 2023, 147, 104898.
[http://dx.doi.org/10.1016/j.jtice.2023.104898] [PMID: 37193294]
[11]
Chen, B.Y.; Lin, Y.H.; Wu, Y.C.; Hsueh, C.C. Deciphering electron-shuttling characteristics of neurotransmitters to stimulate bioelectricity-generating capabilities in microbial fuel cells. Appl. Biochem. Biotechnol., 2020, 191(1), 59-73.
[http://dx.doi.org/10.1007/s12010-020-03242-9] [PMID: 31989437]
[12]
Chen, B.Y.; Liao, J.H.; Hsueh, C.C.; Qu, Z.; Hsu, A.W.; Chang, C.T.; Zhang, S. Deciphering biostimulation strategy of using medicinal herbs and tea extracts for bioelectricity generation in microbial fuel cells. Energy, 2018, 161, 1042-1054.
[http://dx.doi.org/10.1016/j.energy.2018.07.177]
[13]
Chen, B.Y.; Liao, J.H.; Hsu, A.W.; Tsai, P.W.; Hsueh, C.C. Exploring optimal supplement strategy of medicinal herbs and tea extracts for bioelectricity generation in microbial fuel cells. Bioresour. Technol., 2018, 256, 95-101.
[http://dx.doi.org/10.1016/j.biortech.2018.01.152] [PMID: 29433051]
[14]
Guo, L.L.; Qin, L.J.; Xu, B.; Wang, X.Z.; Hsueh, C.C.; Chen, B.Y. Deciphering electron-shuttling characteristics of epinephrine and dopamine for bioenergy extraction using microbial fuel cells. Biochem. Eng. J., 2019, 148, 57-64.
[http://dx.doi.org/10.1016/j.bej.2019.04.018]
[15]
Tsai, P.W.; Tayo, L.L.; Ting, J.U.; Hsieh, C.Y.; Lee, C.J.; Chen, C.L.; Yang, H.C.; Tsai, H.Y.; Hsueh, C.C.; Chen, B.Y. Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells. Ind. Crops Prod., 2023, 191, 115944.
[http://dx.doi.org/10.1016/j.indcrop.2022.115944] [PMID: 36405420]
[16]
Pinzi, L.; Rastelli, G. Molecular docking: Shifting paradigms in drug discovery. Int. J. Mol. Sci., 2019, 20(18), 4331.
[http://dx.doi.org/10.3390/ijms20184331] [PMID: 31487867]
[17]
Liu, Z.; Liu, Y.; Zeng, G.; Shao, B.; Chen, M.; Li, Z.; Jiang, Y.; Liu, Y.; Zhang, Y.; Zhong, H. Application of molecular docking for the degradation of organic pollutants in the environmental remediation: A review. Chemosphere, 2018, 203, 139-150.
[http://dx.doi.org/10.1016/j.chemosphere.2018.03.179] [PMID: 29614407]
[18]
Bicak, B.; Kecel Gunduz, S. Computer-aided drug design of plant-based compounds. In: Isolation, Characterization, and Therapeutic Applications of Natural Bioactive Compounds; IGI Global Publishers, 2022.
[http://dx.doi.org/10.4018/978-1-6684-7337-5.ch013]
[19]
Gnanaraj, C.; Sekar, M.; Fuloria, S.; Swain, S.S.; Gan, S.H.; Chidambaram, K.; Rani, N.N.I.M.; Balan, T.; Stephenie, S.; Lum, P.T.; Jeyabalan, S.; Begum, M.Y.; Chandramohan, V.; Thangavelu, L.; Subramaniyan, V.; Fuloria, N.K. In silico molecular docking analysis of karanjin against Alzheimer’s and Parkinson’s Diseases as a potential natural lead molecule for new drug design, development and therapy. Molecules, 2022, 27(9), 2834.
[http://dx.doi.org/10.3390/molecules27092834] [PMID: 35566187]
[20]
Pratama, M.R.F.; Poerwono, H.; Siswodiharjo, S. ADMET properties of novel 5- O -benzoylpinostrobin derivatives. J. Basic Clin. Physiol. Pharmacol., 2019, 30(6), 20190251.
[http://dx.doi.org/10.1515/jbcpp-2019-0251] [PMID: 31851612]
[21]
Alghamdi, S.S.; Suliman, R.S.; Aljammaz, N.A.; Kahtani, K.M.; Aljatli, D.A.; Albadrani, G.M. Natural products as novel neuroprotective agents; computational predictions of the molecular targets, ADME properties, and safety profile. Plants, 2022, 11(4), 549.
[http://dx.doi.org/10.3390/plants11040549] [PMID: 35214883]
[22]
Kumar, G.P.; Khanum, F. Neuroprotective potential of phytochemicals. Pharmacogn. Rev., 2012, 6(12), 81-90.
[http://dx.doi.org/10.4103/0973-7847.99898] [PMID: 23055633]
[23]
Kumar, V. Potential medicinal plants for CNS disorders: An overview. Phytother. Res., 2006, 20(12), 1023-1035.
[http://dx.doi.org/10.1002/ptr.1970] [PMID: 16909441]
[24]
Russo, A.; Borrelli, F. Bacopa monniera, a reputed nootropic plant: An overview. Phytomedicine, 2005, 12(4), 305-317.
[http://dx.doi.org/10.1016/j.phymed.2003.12.008] [PMID: 15898709]
[25]
Lee, H.; Kim, Y.O.; Kim, H.; Kim, S.Y.; Noh, H.S.; Kang, S.S.; Cho, G.J.; Choi, W.S.; Suk, K. Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J., 2003, 17(13), 1-21.
[http://dx.doi.org/10.1096/fj.03-0057fje] [PMID: 12897065]
[26]
Bitencourt-Ferreira, G.; Veit-Acosta, M.; de Azevedo, W.F., Jr Van der waals potential in protein complexes. Methods Mol. Biol., 2019, 2053, 79-91.
[http://dx.doi.org/10.1007/978-1-4939-9752-7_6] [PMID: 31452100]
[27]
Raschka, S.; Wolf, A.J.; Bemister-Buffington, J.; Kuhn, L.A. Protein–ligand interfaces are polarized: Discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes. J. Comput. Aided Mol. Des., 2018, 32(4), 511-528.
[http://dx.doi.org/10.1007/s10822-018-0105-2] [PMID: 29435780]
[28]
Fu, Y.; Zhao, J.; Chen, Z. Insights into the molecular mechanisms of protein-ligand interactions by molecular docking and molecular dynamics simulation: A case of oligopeptide binding protein. Comput. Math. Methods Med., 2018, 2018, 1-12.
[http://dx.doi.org/10.1155/2018/3502514] [PMID: 30627209]
[29]
Chartier-Harlin, M.C.; Kachergus, J.; Roumier, C.; Mouroux, V.; Douay, X.; Lincoln, S.; Levecque, C.; Larvor, L.; Andrieux, J.; Hulihan, M.; Waucquier, N.; Defebvre, L.; Amouyel, P.; Farrer, M.; Destée, A. α-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet, 2004, 364(9440), 1167-1169.
[http://dx.doi.org/10.1016/S0140-6736(04)17103-1] [PMID: 15451224]
[30]
Ibáñez, P.; Bonnet, A-M.; Débarges, B.; Lohmann, E.; Tison, F.; Agid, Y.; Dürr, A.; Brice, A.; Pollak, P. Causal relation between α-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet, 2004, 364(9440), 1169-1171.
[http://dx.doi.org/10.1016/S0140-6736(04)17104-3] [PMID: 15451225]
[31]
Wilson, C.N.; Mustafa, S.J. Eds.; Adenosine Receptors in Health and Disease; Springer Berlin Heidelberg: Berlin, Heidelberg, 2009, Vol. 193, .
[http://dx.doi.org/10.1007/978-3-540-89615-9_11]
[32]
Olanow, C.W.; Brundin, P. Parkinson’s disease and alpha synuclein: is Parkinson’s disease a prion-like disorder? Mov. Disord., 2013, 28(1), 31-40.
[http://dx.doi.org/10.1002/mds.25373] [PMID: 23390095]
[33]
Teo, K.C.; Ho, S.L. Monoamine oxidase-B (MAO-B) inhibitors: Implications for disease-modification in Parkinson’s disease. Transl. Neurodegener., 2013, 2(1), 19.
[http://dx.doi.org/10.1186/2047-9158-2-19] [PMID: 24011391]
[34]
Choi, J.W.; Jang, B.K.; Cho, N.; Park, J.H.; Yeon, S.K.; Ju, E.J.; Lee, Y.S.; Han, G.; Pae, A.N.; Kim, D.J.; Park, K.D. Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors. Bioorg. Med. Chem., 2015, 23(19), 6486-6496.
[http://dx.doi.org/10.1016/j.bmc.2015.08.012] [PMID: 26337020]
[35]
Siramshetty, V.B.; Nickel, J.; Omieczynski, C.; Gohlke, B.O.; Drwal, M.N.; Preissner, R. WITHDRAWN—a resource for withdrawn and discontinued drugs. Nucleic Acids Res., 2016, 44(D1), D1080-D1086.
[http://dx.doi.org/10.1093/nar/gkv1192] [PMID: 26553801]
[36]
y, M.; Iliya S, S.Z.; Kani YA, M.B.K.; Wali U, A.M.B.; Tahiru A, M.H.Y.; Ahmed AY, M.Y.; Habeeb A, Y.A.; Saeed SA, F.I.B.; Uf, A. Molecular docking, drug-likeness and ADMET analysis of potential inhibitors (Ligands) from carica papaya against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Saudi Journal of Medicine, 2020, 5(5), 222-232.
[http://dx.doi.org/10.36348/sjm.2020.v05i05.002]
[37]
Waring, M.J. Lipophilicity in drug discovery. Expert Opin. Drug Discov., 2010, 5(3), 235-248.
[http://dx.doi.org/10.1517/17460441003605098] [PMID: 22823020]
[38]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[39]
Nisha, C.M.; Kumar, A.; Nair, P.; Gupta, N.; Silakari, C.; Tripathi, T.; Kumar, A. Molecular docking and in silico ADMET study reveals acylguanidine 7a as a potential inhibitor of β -secretase. Adv. Bioinforma., 2016, 2016, 1-6.
[http://dx.doi.org/10.1155/2016/9258578] [PMID: 27190510]
[40]
Pires, D.E.V.; Blundell, T.L.; Ascher, D.B. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. J. Med. Chem., 2015, 58(9), 4066-4072.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00104] [PMID: 25860834]
[41]
Hakkola, J.; Hukkanen, J.; Turpeinen, M.; Pelkonen, O. Inhibition and induction of CYP enzymes in humans: An update. Arch. Toxicol., 2020, 94(11), 3671-3722.
[http://dx.doi.org/10.1007/s00204-020-02936-7] [PMID: 33111191]
[42]
Pelkonen, O.; Turpeinen, M.; Hakkola, J.; Honkakoski, P.; Hukkanen, J.; Raunio, H. Inhibition and induction of human cytochrome P450 enzymes: Current status. Arch. Toxicol., 2008, 82(10), 667-715.
[http://dx.doi.org/10.1007/s00204-008-0332-8] [PMID: 18618097]
[43]
Bardal, S.K.; Waechter, J.E.; Martin, D.S. Pharmacokinetics In Applied pharmacology, 2011, 17-34.
[44]
Alarcón-Herrera, N.; Flores-Maya, S.; Bellido, B.; García-Bores, A.M.; Mendoza, E.; Ávila-Acevedo, G.; Hernández-Echeagaray, E. Protective effects of chlorogenic acid in 3-nitropropionic acid induced toxicity and genotoxicity. Food Chem. Toxicol., 2017, 109(Pt 2), 1018-1025.
[http://dx.doi.org/10.1016/j.fct.2017.04.048] [PMID: 28478101]
[45]
Tajik, N.; Tajik, M.; Mack, I.; Enck, P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: A comprehensive review of the literature. Eur. J. Nutr., 2017, 56(7), 2215-2244.
[http://dx.doi.org/10.1007/s00394-017-1379-1] [PMID: 28391515]
[46]
Conte, A.; Pellegrini, S.; Tagliazucchi, D. Synergistic protection of PC12 cells from β-amyloid toxicity by resveratrol and catechin. Brain Res. Bull., 2003, 62(1), 29-38.
[http://dx.doi.org/10.1016/j.brainresbull.2003.08.001] [PMID: 14596889]
[47]
Ahmed, H.; Khan, M.A.; Ali Zaidi, S.A.; Muhammad, S. In silico and in vivo: Evaluating the therapeutic potential of kaempferol, quercetin, and catechin to treat chronic epilepsy in a rat model. Front. Bioeng. Biotechnol., 2021, 9, 754952.

© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version410msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[06:14:26] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[06:14:27] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[06:14:27] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[06:14:27] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[06:14:27] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (130ms)time
  • Application (281ms)time
  • 1 x Application (68.37%)
    281ms
    1 x Booting (31.63%)
    130ms
    10 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    35 statements were executed, 2 of which were duplicates, 33 unique. Show only duplicated185ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('316524592','',1,1740550467,1740550467) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740550467
      1.11msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('316524592','/article/135274',1,1740550467,1740550467)
      160μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 316524592 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 316524592) limit 1
      15.8msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 316524592
      • 1: 316524592
      • 2: 316524592
      • 3: 316524592
      • 4: 316524592
      • 5: 316524592
      • 6: 316524592
      • 7: 316524592
      • 8: 316524592
      • 9: 316524592
      • 10: 316524592
      • 11: 316524592
      • 12: 316524592
      • 13: 316524592
      • 14: 316524592
      • 15: 316524592
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=135274
      740μsalphaeurekaselec_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` = 57 limit 1
      800μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 57
      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=57) and sj.journal_id!=57 group by `j`.`nid`) as `aggregate_table`
      1.63msalphaeurekaselec_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=57) and sj.journal_id!=57 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.35msalphaeurekaselec_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=57) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.48msalphaeurekaselec_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=57) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.23msalphaeurekaselec_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` = '135274'
      310μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 135274
      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` = '135274'
      13.52msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 135274
      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` = '135274' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      7.57msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 135274
      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
      1.09msalphaeurekaselec_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
      730μsalphaeurekaselec_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 = 57 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      46.59msalphaeurekaselec_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 = 57 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      54.16msalphaeurekaselec_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 = 57 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      17.94msalphaeurekaselec_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` = 135274 limit 1
      260μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 135274
      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 = 135274 and content_type = 'article' order by status desc limit 1
      340μsalphaeurekaselec_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` = 222275 limit 1
      260μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 222275
      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
      280μsalphaeurekaselec_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` = 'LDDD' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      320μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: LDDD
      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 = '135274' 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) )
      520μsalphaeurekaselec_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 = '13450' 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) )
      450μsalphaeurekaselec_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 = '3468' 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) )
      400μsalphaeurekaselec_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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3468) 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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3468) 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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3468)
      6.16msalphaeurekaselec_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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13450) 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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13450) 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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 13450)
      830μsalphaeurekaselec_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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 135274) 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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 135274) 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 <= 316524592 and j.to_ip >=316524592 )) and ((j.from_date <= 1740550467 and j.to_date >= 1740550467 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 135274)
      690μsalphaeurekaselec_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` < '3030' and is_uploaded = 1 and issue_id = 13450 order by cast(first_page as SIGNED) desc limit 1
      560μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 3030
      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` > '3038' and is_uploaded = 1 and issue_id = 13450 order by cast(first_page as SIGNED) asc limit 1
      570μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 3038
      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'
      200μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      240μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 135274 limit 1
      2.4msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 135274
      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` = 57 and `b`.`banner_from_date` <= 1740550467 and `b`.`banner_to_date` >= 1740550467 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.17msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 57
      • 3: 1740550467
      • 4: 1740550467
      • 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='8ef45935fe2712e5dd176461cb6d3d82'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        uqlMKrD6H3GhLCxtZhdoglWuYa640p9D9ubqFGAe
        uc_cart_id
        8ef45935fe2712e5dd176461cb6d3d82
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/135274" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/135274
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IjBjSlZBMUo1Z0JEY3AwRkkvZHUzZFE9PSIsInZhbHVlIjoiM096dFlqUVRLcVJFT0s1SkdoeFVsNnBoYk9hVnptMTdwVzFOT29TMjQ0TT0iLCJtYWMiOiI3MWQ0MGVkNTBiMjZiOWQ4NGJmYjhlYzIyYTRiNjFiNjMwYmJkYjdlY2JlMzM1MWY2M2E1ZGM4MGY3ODFiOTk1IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6IjBjSlZBMUo1Z0JEY3AwRkkvZHUzZFE9PSIsInZhbHVlIjoiM096dFlqUVRLcVJFT0s1SkdoeFVsNnBoYk9hVnptMTdwVzFOT29TMjQ0TT0iLCJtYWMiOiI3MWQ0MGVkNTBiMjZi" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 26 Feb 2025 06:14:27 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjN2VUF6c3RCaG05MFNicHlvNVNTNnc9PSIsInZhbHVlIjoiTnlsR29PT3VIazRQbEJLUmZ6Y1l3c2NoZWV4Mm1TTmZXZkpSVDdoQ0l0UmJNWnBlYzhVOHFvMmVJUW1sSERWZ2trZkFFNEdjYi9uajFlTWI0eDBHRXM4TVNCbmZZUXV2RVIvRnBqeWV5cW8rZjhSejk2RUlLb0kvZ1N5WUh2TnEiLCJtYWMiOiI0NTRlNWI1ODMxODA5MjcxOTY3NWFjZTgyMWRmNDIzNTZmZmYxNDlmOTM2NWE0MGVhZDFkZmEwMTY2OGUxZGMwIiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 18:14:27 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjN2VUF6c3RCaG05MFNicHlvNVNTNnc9PSIsInZhbHVlIjoiTnlsR29PT3VIazRQbEJLUmZ6Y1l3c2NoZWV4Mm1TTmZXZkpSVDdoQ0l0UmJNWnBlYzhVOHFvMmVJUW1sSERWZ2trZkFFN" 1 => "alphaeurekaselectnet_session=eyJpdiI6InkrZXZtcHRxdk5SYUdTelduajdBNWc9PSIsInZhbHVlIjoiZmVFekxQV0lINE5pVFdxL21wdzdvN0xSQU5ZdDZaaFRvYkF3YzhpTlhCQ3BJQTVDSGE1dC9rYWk2RU8wN3BhSkRraXl2QjR6b2RqOXdIQ3AxbDc1UE9xU0Fkd1NVS1JOaWRuMlVrYWh2TFE4aGgxQ1c4ME9IN0pVRHNESEd2N2ciLCJtYWMiOiI2ZDY3NjcwMGRhM2RiNTYzMWRkOGNiMjk2YTQ0ZGQ4ZTc3MWU5NGFkMjgxZTgxMmVhODRhYmUxZjIwOTY4OTQyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InkrZXZtcHRxdk5SYUdTelduajdBNWc9PSIsInZhbHVlIjoiZmVFekxQV0lINE5pVFdxL21wdzdvN0xSQU5ZdDZaaFRvYkF3YzhpTlhCQ3BJQTVDSGE1dC9rYWk" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjN2VUF6c3RCaG05MFNicHlvNVNTNnc9PSIsInZhbHVlIjoiTnlsR29PT3VIazRQbEJLUmZ6Y1l3c2NoZWV4Mm1TTmZXZkpSVDdoQ0l0UmJNWnBlYzhVOHFvMmVJUW1sSERWZ2trZkFFNEdjYi9uajFlTWI0eDBHRXM4TVNCbmZZUXV2RVIvRnBqeWV5cW8rZjhSejk2RUlLb0kvZ1N5WUh2TnEiLCJtYWMiOiI0NTRlNWI1ODMxODA5MjcxOTY3NWFjZTgyMWRmNDIzNTZmZmYxNDlmOTM2NWE0MGVhZDFkZmEwMTY2OGUxZGMwIiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 18:14:27 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjN2VUF6c3RCaG05MFNicHlvNVNTNnc9PSIsInZhbHVlIjoiTnlsR29PT3VIazRQbEJLUmZ6Y1l3c2NoZWV4Mm1TTmZXZkpSVDdoQ0l0UmJNWnBlYzhVOHFvMmVJUW1sSERWZ2trZkFFN" 1 => "alphaeurekaselectnet_session=eyJpdiI6InkrZXZtcHRxdk5SYUdTelduajdBNWc9PSIsInZhbHVlIjoiZmVFekxQV0lINE5pVFdxL21wdzdvN0xSQU5ZdDZaaFRvYkF3YzhpTlhCQ3BJQTVDSGE1dC9rYWk2RU8wN3BhSkRraXl2QjR6b2RqOXdIQ3AxbDc1UE9xU0Fkd1NVS1JOaWRuMlVrYWh2TFE4aGgxQ1c4ME9IN0pVRHNESEd2N2ciLCJtYWMiOiI2ZDY3NjcwMGRhM2RiNTYzMWRkOGNiMjk2YTQ0ZGQ4ZTc3MWU5NGFkMjgxZTgxMmVhODRhYmUxZjIwOTY4OTQyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InkrZXZtcHRxdk5SYUdTelduajdBNWc9PSIsInZhbHVlIjoiZmVFekxQV0lINE5pVFdxL21wdzdvN0xSQU5ZdDZaaFRvYkF3YzhpTlhCQ3BJQTVDSGE1dC9rYWk" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "uqlMKrD6H3GhLCxtZhdoglWuYa640p9D9ubqFGAe" "uc_cart_id" => "8ef45935fe2712e5dd176461cb6d3d82" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/135274" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-26 06:14:27GET/article/135274510351