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Current Nanoscience

Editor-in-Chief

ISSN (Print): 1573-4137
ISSN (Online): 1875-6786

General Research Article

Iron Oxide Nanoparticles Synthesized Via Green Tea Extract for Doxorubicin Delivery

Author(s): Lei Nie*, Chenlei Cai, Meng Sun, Fang Zhang, Lingyun Zheng, Qi Peng, Amin Shavandi* and Shoufeng Yang

Volume 17, Issue 4, 2021

Published on: 29 October, 2020

Page: [646 - 657] Pages: 12

DOI: 10.2174/1573413716999201029205654

open access plus

Abstract

Background: Due to the limitation of conventional cancer treatment using chemotherapy, the nanoparticle therapeutics have shown enhanced efficacy with alleviating side effects.

Objective: The aim of this study was to prepare the superparamagnetic iron oxide nanoparticles (TC- SPION) for doxorubicin (DOX) loading and delivery.

Methods: Here, we reported a simple green strategy to fabricate T-C-SPION using green tea extract and citric acid. Also, the anti-cancer drug, DOX, was used as a model drug to fabricate DOX-loaded nanoparticles.

Results: The formed T-C-SPION nanoparticles were spherical with a diameter of 23.8 ± 0.8 nm, as confirmed by Transmission Electron Microscopy (TEM). Besides, Dynamic Light Scattering (DLS) revealed that the prepared nanoparticles were water-dispersible and stable while stored in water for 6 weeks. The CCK-8 assay showed T-C-SPION to have a good cytocompatibility using different iron concentrations (10 ~ 120 ug/mL). Furthermore, T-C-SPION had a higher DOX encapsulation efficiency (Eencaps), around 43.2 ± 1.8 %, which resulted in a lagged release profile of DOX, compared to other types of iron oxide nanoparticles using green tea or citric acid alone. Next, cell viability assay indicated that T-C-SPION with a higher Eencaps showed superior and sustained cytotoxicity compared to the control group.

Conclusion: The developed iron oxide nanoparticles synthesized by green tea extract and citric acid in this paper could be considered as a potential drug carrier for cancer therapy applications.

Keywords: Nanoparticles, iron oxide, green tea, citric acid, doxorubicin, drug delivery, cytocompatibility.

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[1]
Nune, S.K.; Chanda, N.; Shukla, R.; Katti, K.; Kulkarni, R.R.; Thilakavathi, S.; Mekapothula, S.; Kannan, R.; Katti, K.V. Green nanotechnology from tea: Phytochemicals in tea as building blocks for production of biocompatible gold nanoparticles. J. Mater. Chem., 2009, 19(19), 2912-2920.
[http://dx.doi.org/10.1039/b822015h] [PMID: 20161162]
[2]
Hamer, M. The beneficial effects of tea on immune function and inflammation: a review of evidence from in vitro, animal, and human research. Nutr. Res., 2007, 27(7), 373-379.
[http://dx.doi.org/10.1016/j.nutres.2007.05.008]
[3]
Yang, C.S.; Lambert, J.D.; Ju, J.; Lu, G.; Sang, S. Tea and cancer prevention: molecular mechanisms and human relevance. Toxicol. Appl. Pharmacol., 2007, 224(3), 265-273.
[http://dx.doi.org/10.1016/j.taap.2006.11.024] [PMID: 17234229]
[4]
Hodgson, J.M. Effects of tea and tea flavonoids on endothelial function and blood pressure: a brief review. Clin. Exp. Pharmacol. Physiol., 2006, 33(9), 838-841.
[http://dx.doi.org/10.1111/j.1440-1681.2006.04450.x] [PMID: 16922817]
[5]
Cabrera, C.; Artacho, R.; Giménez, R. Beneficial effects of green tea--a review. J. Am. Coll. Nutr., 2006, 25(2), 79-99.
[http://dx.doi.org/10.1080/07315724.2006.10719518] [PMID: 16582024]
[6]
Chacko, S.M.; Thambi, P.T.; Kuttan, R.; Nishigaki, I. Beneficial effects of green tea: a literature review. Chin. Med., 2010, 5(1), 13.
[http://dx.doi.org/10.1186/1749-8546-5-13] [PMID: 20370896]
[7]
Jankun, J.; Selman, S.H.; Swiercz, R.; Skrzypczak-Jankun, E. Why drinking green tea could prevent cancer. Nature, 1997, 387(6633), 561.
[http://dx.doi.org/10.1038/42381] [PMID: 9177339]
[8]
Fujiki, H.; Sueoka, E.; Watanabe, T.; Suganuma, M. Primary cancer prevention by green tea, and tertiary cancer prevention by the combination of green tea catechins and anticancer compounds. J. Cancer Prev., 2015, 20(1), 1-4.
[http://dx.doi.org/10.15430/JCP.2015.20.1.1] [PMID: 25853098]
[9]
Miller, K.D.; Siegel, R.L.; Lin, C.C.; Mariotto, A.B.; Kramer, J.L.; Rowland, J.H.; Stein, K.D.; Alteri, R.; Jemal, A. Cancer treatment and survivorship statistics, 2016. CA Cancer J. Clin., 2016, 66(4), 271-289.
[http://dx.doi.org/10.3322/caac.21349] [PMID: 27253694]
[10]
Vanneman, M.; Dranoff, G. Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer, 2012, 12(4), 237-251.
[http://dx.doi.org/10.1038/nrc3237] [PMID: 22437869]
[11]
Fukuhara, H.; Ino, Y.; Todo, T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer Sci., 2016, 107(10), 1373-1379.
[http://dx.doi.org/10.1111/cas.13027] [PMID: 27486853]
[12]
Kennedy, L.C.; Bickford, L.R.; Lewinski, N.A.; Coughlin, A.J.; Hu, Y.; Day, E.S.; West, J.L.; Drezek, R.A. A new era for cancer treatment: gold-nanoparticle-mediated thermal therapies. Small, 2011, 7(2), 169-183.
[http://dx.doi.org/10.1002/smll.201000134] [PMID: 21213377]
[13]
Chen, J.; Glaus, C.; Laforest, R.; Zhang, Q.; Yang, M.; Gidding, M.; Welch, M.J.; Xia, Y. Gold nanocages as photothermal transducers for cancer treatment. Small, 2010, 6(7), 811-817.
[http://dx.doi.org/10.1002/smll.200902216] [PMID: 20225187]
[14]
Davis, M.E.; Chen, Z.G.; Shin, D.M. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov., 2008, 7(9), 771-782.
[http://dx.doi.org/10.1038/nrd2614] [PMID: 18758474]
[15]
Gabizon, A.; Shmeeda, H.; Barenholz, Y. Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin. Pharmacokinet., 2003, 42(5), 419-436.
[http://dx.doi.org/10.2165/00003088-200342050-00002] [PMID: 12739982]
[16]
Zhu, L.; Wang, D.; Wei, X.; Zhu, X.; Li, J.; Tu, C.; Su, Y.; Wu, J.; Zhu, B.; Yan, D. Multifunctional pH-sensitive superparamagnetic iron-oxide nanocomposites for targeted drug delivery and MR imaging. J. Control. Release, 2013, 169(3), 228-238.
[http://dx.doi.org/10.1016/j.jconrel.2013.02.015] [PMID: 23485450]
[17]
Zanganeh, S.; Hutter, G.; Spitler, R.; Lenkov, O.; Mahmoudi, M.; Shaw, A.; Pajarinen, J.S.; Nejadnik, H.; Goodman, S.; Moseley, M.; Coussens, L.M.; Daldrup-Link, H.E. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat. Nanotechnol., 2016, 11(11), 986-994.
[http://dx.doi.org/10.1038/nnano.2016.168] [PMID: 27668795]
[18]
Sakulkhu, U.; Mahmoudi, M.; Maurizi, L.; Coullerez, G.; Hofmann-Amtenbrink, M.; Vries, M.; Motazacker, M.; Rezaee, F.; Hofmann, H. Significance of surface charge and shell material of superparamagnetic iron oxide nanoparticle (SPION) based core/shell nanoparticles on the composition of the protein corona. Biomater. Sci., 2015, 3(2), 265-278.
[http://dx.doi.org/10.1039/C4BM00264D] [PMID: 26218117]
[19]
Espinosa, A.; Di Corato, R.; Kolosnjaj-Tabi, J.; Flaud, P.; Pellegrino, T.; Wilhelm, C. Duality of iron oxide nanoparticles in cancer therapy: Amplification of heating efficiency by magnetic hyperthermia and photothermal bimodal treatment. ACS Nano, 2016, 10(2), 2436-2446.
[http://dx.doi.org/10.1021/acsnano.5b07249] [PMID: 26766814]
[20]
Mahmoudi, M.; Sahraian, M.A.; Shokrgozar, M.A.; Laurent, S. Superparamagnetic iron oxide nanoparticles: promises for diagnosis and treatment of multiple sclerosis. ACS Chem. Neurosci., 2011, 2(3), 118-140.
[http://dx.doi.org/10.1021/cn100100e] [PMID: 22778862]
[21]
Li, W.; Tutton, S.; Vu, A.T.; Pierchala, L.; Li, B.S.Y.; Lewis, J.M.; Prasad, P.V.; Edelman, R.R. First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent. J. Magn. Reson. Imaging, 2005, 21(1), 46-52.
[http://dx.doi.org/10.1002/jmri.20235] [PMID: 15611942]
[22]
Szekeres, M.; Tóth, I.Y.; Illés, E.; Hajdú, A.; Zupkó, I.; Farkas, K.; Oszlánczi, G.; Tiszlavicz, L.; Tombácz, E. Chemical and colloidal stability of carboxylated core-shell magnetite nanoparticles designed for biomedical applications. Int. J. Mol. Sci., 2013, 14(7), 14550-14574.
[http://dx.doi.org/10.3390/ijms140714550] [PMID: 23857054]
[23]
Thanh, N.T.K.; Maclean, N.; Mahiddine, S. Mechanisms of nucleation and growth of nanoparticles in solution. Chem. Rev., 2014, 114(15), 7610-7630.
[http://dx.doi.org/10.1021/cr400544s] [PMID: 25003956]
[24]
Gul, S.; Khan, S.B.; Rehman, I.U.; Khan, M.A.; Khan, M.I. A comprehensive review of magnetic nanomaterials modern day theranostics. Front. Mater., 2019, 6, 179.
[http://dx.doi.org/10.3389/fmats.2019.00179]
[25]
Roth, H-C.; Schwaminger, S.P.; Schindler, M.; Wagner, F.E.; Berensmeier, S. Influencing factors in the CO-precipitation process of superparamagnetic iron oxide nano particles: A model based study. J. Magn. Magn. Mater., 2015, 377, 81-89.
[http://dx.doi.org/10.1016/j.jmmm.2014.10.074]
[26]
Li, L.; Mak, K.Y.; Leung, C.W.; Chan, K.Y.; Chan, W.K.; Zhong, W.; Pong, P.W.T. Effect of synthesis conditions on the properties of citric-acid coated iron oxide nanoparticles. Microelectron. Eng., 2013, 110, 329-334.
[http://dx.doi.org/10.1016/j.mee.2013.02.045]
[27]
Răcuciu, M.; Creangă, D.E.; Airinei, A. Citric-acid-coated magnetite nanoparticles for biological applications. Eur. Phys J.E Soft Matter, 2006, 21(2), 117-121.
[http://dx.doi.org/10.1140/epje/i2006-10051-y] [PMID: 17180642]
[28]
Laurent, S.; Forge, D.; Port, M.; Roch, A.; Robic, C.; Vander Elst, L.; Muller, R.N. Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev., 2008, 108(6), 2064-2110.
[http://dx.doi.org/10.1021/cr068445e] [PMID: 18543879]
[29]
Li, S.; Zhang, T.; Tang, R.; Qiu, H.; Wang, C.; Zhou, Z. Solvothermal synthesis and characterization of monodisperse superparamagnetic iron oxide nanoparticles. J. Magn. Magn. Mater., 2015, 379, 226-231.
[http://dx.doi.org/10.1016/j.jmmm.2014.12.054]
[30]
Park, J.; Lee, E.; Hwang, N-M.; Kang, M.; Kim, S.C.; Hwang, Y.; Park, J-G.; Noh, H-J.; Kim, J-Y.; Park, J-H.; Hyeon, T. One-nanometer-scale size-controlled synthesis of monodisperse magnetic iron oxide nanoparticles. Angew. Chem. Int. Ed. Engl., 2005, 44(19), 2873-2877.
[http://dx.doi.org/10.1002/anie.200461665] [PMID: 15798989]
[31]
Park, J.; An, K.; Hwang, Y.; Park, J-G.; Noh, H-J.; Kim, J-Y.; Park, J-H.; Hwang, N-M.; Hyeon, T. Ultra-large-scale syntheses of monodisperse nanocrystals. Nat. Mater., 2004, 3(12), 891-895.
[http://dx.doi.org/10.1038/nmat1251] [PMID: 15568032]
[32]
Hufschmid, R.; Arami, H.; Ferguson, R.M.; Gonzales, M.; Teeman, E.; Brush, L.N.; Browning, N.D.; Krishnan, K.M. Synthesis of phase-pure and monodisperse iron oxide nanoparticles by thermal decomposition. Nanoscale, 2015, 7(25), 11142-11154.
[http://dx.doi.org/10.1039/C5NR01651G] [PMID: 26059262]
[33]
Korpany, K.V.; Mottillo, C.; Bachelder, J.; Cross, S.N.; Dong, P.; Trudel, S.; Friščić, T.; Blum, A.S. One-step ligand exchange and switching from hydrophobic to water-stable hydrophilic superparamagnetic iron oxide nanoparticles by mechanochemical milling. Chem. Commun. (Camb.), 2016, 52(14), 3054-3057.
[http://dx.doi.org/10.1039/C5CC07107K] [PMID: 26794225]
[34]
Bixner, O.; Lassenberger, A.; Baurecht, D.; Reimhult, E. Complete exchange of the hydrophobic dispersant shell on monodisperse superparamagnetic iron oxide nanoparticles. Langmuir, 2015, 31(33), 9198-9204.
[http://dx.doi.org/10.1021/acs.langmuir.5b01833] [PMID: 26226071]
[35]
Illés, E.; Szekeres, M.; Tóth, I.Y.; Szabó, Á.; Iván, B.; Turcu, R.; Vékás, L.; Zupkó, I.; Jaics, G.; Tombácz, E. Multifunctional PEG-carboxylate copolymer coated superparamagnetic iron oxide nanoparticles for biomedical application. J. Magn. Magn. Mater., 2018, 451, 710-720.
[http://dx.doi.org/10.1016/j.jmmm.2017.11.122]
[36]
Karimzadeh, I.; Aghazadeh, M.; Doroudi, T.; Ganjali, M.R.; Kolivand, P.H. Superparamagnetic iron oxide (Fe3O4) nanoparticles coated with PEG/PEI for biomedical applications: A facile and scalable preparation route based on the cathodic electrochemical deposition method. Adv. Phys. Chem., 2017, 2017, 9437487.
[http://dx.doi.org/10.1155/2017/9437487]
[37]
Shavandi, A.; Saeedi, P.; Ali, M.A.; Jalalvandi, E. Green synthesis of polysaccharide-based inorganic nanoparticles and biomedical aspects. Functional Polysaccharides for Biomedical Applications; Maiti, S; Jana, S., Ed.; Woodhead Publishing, 2019, pp. 267-304.
[http://dx.doi.org/10.1016/B978-0-08-102555-0.00008-X]
[38]
Asadi, H.; Khoee, S.; Deckers, R. Polymer-grafted superparamagnetic iron oxide nanoparticles as a potential stable system for magnetic resonance imaging and doxorubicin delivery. RSC Advances, 2016, 6(87), 83963-83972.
[http://dx.doi.org/10.1039/C6RA20398A]
[39]
Hoag, G.E.; Collins, J.B.; Holcomb, J.L.; Hoag, J.R.; Nadagouda, M.N.; Varma, R.S. Degradation of bromothymol blue by ‘greener’ nano-scale zero-valent iron synthesized using tea polyphenols. J. Mater. Chem., 2009, 19(45), 8671-8677.
[http://dx.doi.org/10.1039/b909148c]
[40]
Tran, T.T-D.; Van Vo, T.; Tran, P.H-L. Design of iron oxide nanoparticles decorated oleic acid and bovine serum albumin for drug delivery. Chem. Eng. Res. Des., 2015, 94, 112-118.
[http://dx.doi.org/10.1016/j.cherd.2014.12.016]
[41]
Saraswathy, A.; Nazeer, S.S.; Jeevan, M.; Nimi, N.; Arumugam, S.; Harikrishnan, V.S.; Varma, P.R.H.; Jayasree, R.S. Citrate coated iron oxide nanoparticles with enhanced relaxivity for in vivo magnetic resonance imaging of liver fibrosis. Colloids Surf. B Biointerfaces, 2014, 117, 216-224.
[http://dx.doi.org/10.1016/j.colsurfb.2014.02.034] [PMID: 24646453]
[42]
Shahwan, T.; Abu Sirriah, S.; Nairat, M.; Boyacı, E.; Eroğlu, A.E.; Scott, T.B.; Hallam, K.R. Green synthesis of iron nanoparticles and their application as a fenton-like catalyst for the degradation of aqueous cationic and anionic dyes. Chem. Eng. J., 2011, 172(1), 258-266.
[http://dx.doi.org/10.1016/j.cej.2011.05.103]
[43]
Shavandi, A.; Bekhit, A.E.A.; Saeedi, P.; Izadifar, Z.; Bekhit, A.A.; Khademhosseini, A. Polyphenol uses in biomaterials engineering. Biomaterials, 2018, 167, 91-106.
[http://dx.doi.org/10.1016/j.biomaterials.2018.03.018] [PMID: 29567389]
[44]
Huang, L.; Weng, X.; Chen, Z.; Megharaj, M.; Naidu, R. Green synthesis of iron nanoparticles by various tea extracts: comparative study of the reactivity. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2014, 130, 295-301.
[http://dx.doi.org/10.1016/j.saa.2014.04.037] [PMID: 24793479]
[45]
Wang, T.; Lin, J.; Chen, Z.; Megharaj, M.; Naidu, R. green synthesized iron nanoparticles by green tea and eucalyptus leaves extracts used for removal of nitrate in aqueous solution. J. Clean. Prod., 2014, 83, 413-419.
[http://dx.doi.org/10.1016/j.jclepro.2014.07.006]
[46]
Das, R.K.; Borthakur, B.B.; Bora, U. Green synthesis of gold nanoparticles using ethanolic leaf extract of Centella asiatica. Mater. Lett., 2010, 64(13), 1445-1447.
[http://dx.doi.org/10.1016/j.matlet.2010.03.051]
[47]
Quinto, C.A.; Mohindra, P.; Tong, S.; Bao, G. Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment. Nanoscale, 2015, 7(29), 12728-12736.
[http://dx.doi.org/10.1039/C5NR02718G] [PMID: 26154916]
[48]
Kim, B.H.; Lee, N.; Kim, H.; An, K.; Park, Y.I.; Choi, Y.; Shin, K.; Lee, Y.; Kwon, S.G.; Na, H.B.; Park, J-G.; Ahn, T-Y.; Kim, Y-W.; Moon, W.K.; Choi, S.H.; Hyeon, T. Large-scale synthesis of uniform and extremely small-sized iron oxide nanoparticles for high-resolution T1 magnetic resonance imaging contrast agents. J. Am. Chem. Soc., 2011, 133(32), 12624-12631.
[http://dx.doi.org/10.1021/ja203340u] [PMID: 21744804]
[49]
Pereira, C.; Pereira, A.M.; Fernandes, C.; Rocha, M.; Mendes, R.; Fernández-García, M.P.; Guedes, A.; Tavares, P.B.; Grenèche, J-M.; Araújo, J.P.; Freire, C. Superparamagnetic MFe2O4 (M = Fe, Co, Mn) nanoparticles: Tuning the particle size and magnetic properties through a novel one-step coprecipitation route. Chem. Mater., 2012, 24(8), 1496-1504.
[http://dx.doi.org/10.1021/cm300301c]
[50]
Xuan, S.; Wang, Y-X.J.; Yu, J.C.; Leung, K.C-F. Tuning the grain size and particle size of superparamagnetic Fe3O4 microparticles. Chem. Mater., 2009, 21(21), 5079-5087.
[http://dx.doi.org/10.1021/cm901618m]
[51]
Patsula, V.; Moskvin, M.; Dutz, S.; Horák, D. Size-dependent magnetic properties of iron oxide nanoparticles. J. Phys. Chem. Solids, 2016, 88, 24-30.
[http://dx.doi.org/10.1016/j.jpcs.2015.09.008]
[52]
Rezayan, A.H.; Mousavi, M.; Kheirjou, S.; Amoabediny, G.; Ardestani, M.S.; Mohammadnejad, J. Monodisperse magnetite (Fe3O4) nanoparticles modified with water soluble polymers for the diagnosis of breast cancer by MRI method. J. Magn. Magn. Mater., 2016, 420, 210-217.
[http://dx.doi.org/10.1016/j.jmmm.2016.07.003]
[53]
Korpany, K.V.; Habib, F.; Murugesu, M.; Blum, A.S. Stable water-soluble iron oxide nanoparticles using tiron. Mater. Chem. Phys., 2013, 138(1), 29-37.
[http://dx.doi.org/10.1016/j.matchemphys.2012.10.015]
[54]
Petri-Fink, A.; Steitz, B.; Finka, A.; Salaklang, J.; Hofmann, H. Effect of cell media on polymer coated superparamagnetic iron oxide nanoparticles (SPIONs): colloidal stability, cytotoxicity, and cellular uptake studies. Eur. J. Pharm. Biopharm., 2008, 68(1), 129-137.
[http://dx.doi.org/10.1016/j.ejpb.2007.02.024] [PMID: 17881203]
[55]
Naqvi, S.; Samim, M.; Abdin, M.; Ahmed, F.J.; Maitra, A.; Prashant, C.; Dinda, A.K. Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress. Int. J. Nanomedicine, 2010, 5, 983-989.
[http://dx.doi.org/10.2147/IJN.S13244] [PMID: 21187917]
[56]
Mahmoudi, M.; Simchi, A.; Milani, A.S.; Stroeve, P. Cell toxicity of superparamagnetic iron oxide nanoparticles. J. Colloid Interface Sci., 2009, 336(2), 510-518.
[http://dx.doi.org/10.1016/j.jcis.2009.04.046] [PMID: 19476952]
[57]
Lee, N.; Yoo, D.; Ling, D.; Cho, M.H.; Hyeon, T.; Cheon, J. Iron oxide based nanoparticles for multimodal imaging and magnetoresponsive therapy. Chem. Rev., 2015, 115(19), 10637-10689.
[http://dx.doi.org/10.1021/acs.chemrev.5b00112] [PMID: 26250431]
[58]
Xu, H-L.; Mao, K-L.; Huang, Y-P.; Yang, J-J.; Xu, J.; Chen, P-P.; Fan, Z-L.; Zou, S.; Gao, Z-Z.; Yin, J-Y.; Xiao, J.; Lu, C-T.; Zhang, B-L.; Zhao, Y-Z. Glioma-targeted superparamagnetic iron oxide nanoparticles as drug-carrying vehicles for theranostic effects. Nanoscale, 2016, 8(29), 14222-14236.
[http://dx.doi.org/10.1039/C6NR02448C] [PMID: 27396404]
[59]
Dai, Y.; Yang, D.; Ma, P.; Kang, X.; Zhang, X.; Li, C.; Hou, Z.; Cheng, Z.; Lin, J. Doxorubicin conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles for therapy and sensing of drug delivery by luminescence resonance energy transfer. Biomaterials, 2012, 33(33), 8704-8713.
[http://dx.doi.org/10.1016/j.biomaterials.2012.08.029] [PMID: 22938822]

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      • 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 ('51271243','/article/111052',1,1740515032,1740515032)
      190μsalphaeurekaselec_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 >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) 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 >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) 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 >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) 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 >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) 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 >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) 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 >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 51271243 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51271243) limit 1
      15.84msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 51271243
      • 1: 51271243
      • 2: 51271243
      • 3: 51271243
      • 4: 51271243
      • 5: 51271243
      • 6: 51271243
      • 7: 51271243
      • 8: 51271243
      • 9: 51271243
      • 10: 51271243
      • 11: 51271243
      • 12: 51271243
      • 13: 51271243
      • 14: 51271243
      • 15: 51271243
      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=111052
      950μsalphaeurekaselec_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` = 27 limit 1
      2.21msalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 27
      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=27) and sj.journal_id!=27 group by `j`.`nid`) as `aggregate_table`
      810μsalphaeurekaselec_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=27) and sj.journal_id!=27 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      630μsalphaeurekaselec_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=27) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      1.93msalphaeurekaselec_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=27) 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` = '111052'
      860μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 111052
      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` = '111052'
      560μsalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 111052
      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` = '111052' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.05msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 111052
      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
      260μsalphaeurekaselec_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
      460μsalphaeurekaselec_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 = 27 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      27.17msalphaeurekaselec_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 = 27 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      10.72msalphaeurekaselec_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 = 27 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      6.8msalphaeurekaselec_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` = 111052 limit 1
      220μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 111052
      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 = 111052 and content_type = 'article' order by status desc limit 1
      320μsalphaeurekaselec_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 a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 16 and cd.sub_disease_id = 454 and content_id!=111052 and cd.content_type = 'article' order by rand() limit 20
      30.41msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 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` = 187397 limit 1
      230μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 187397
      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
      250μsalphaeurekaselec_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` = 'CNANO' 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: CNANO
      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 = '111052' 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) )
      400μsalphaeurekaselec_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 * from `article` where `first_page` < '646' and is_uploaded = 1 and issue_id = 10795 order by cast(first_page as SIGNED) desc limit 1
      570μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 646
      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` > '657' and is_uploaded = 1 and issue_id = 10795 order by cast(first_page as SIGNED) asc limit 1
      420μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 657
      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'
      180μsalphaeurekaselec_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
      220μsalphaeurekaselec_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` = 111052 limit 1
      2.36msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 111052
      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` = 27 and `b`.`banner_from_date` <= 1740515032 and `b`.`banner_to_date` >= 1740515032 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.14msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 27
      • 3: 1740515032
      • 4: 1740515032
      • 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` = 27 and `b`.`banner_from_date` <= 1740515032 and `b`.`banner_to_date` >= 1740515032 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.11msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 27
      • 3: 1740515032
      • 4: 1740515032
      • 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='54f5bdfe60fbf4f2526ceabba7fdae4e'
      280μsalphaeurekaselec_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
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:23:52GET/article/111052414321