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Current Chemical Biology

Editor-in-Chief

ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Review Article

Tellurium-containing Thiol-peroxidase-like Antioxidants and their Catalytic Mechanism

Author(s): Antonella Capperucci and Damiano Tanini*

Volume 17, Issue 1, 2023

Published on: 19 December, 2022

Page: [13 - 25] Pages: 13

DOI: 10.2174/2212796817666221121155138

Abstract

The development of novel small molecules with effective catalytic antioxidant properties is highly sought after. A wide array of structurally diverse selenium- and tellurium-containing glutathione peroxidase mimics have been studied over the past two decades. Within this arena, organotellurium compounds generally exhibit higher catalytic properties with respect to selenium-containing analogues. Different mechanisms accounting for the thiol-peroxidase-like activity of various classes of organotellurium derivatives have been proposed. This review documents developments in this area and provides an overview of the catalytic mechanisms proposed for the various classes of telluriumcontaining thiol-peroxidase-like-catalysts.

Graphical Abstract

[1]
Klotz, L.O.; Kröncke, K.D.; Buchczyk, D.P.; Sies, H. Role of copper, zinc, selenium and tellurium in the cellular defense against oxidative and nitrosative stress. J. Nutr., 2003, 133(5)(Suppl. 1), 1448S-1451S.
[http://dx.doi.org/10.1093/jn/133.5.1448S] [PMID: 12730440]
[2]
Barchielli, G.; Capperucci, A.; Tanini, D. The role of selenium in pathologies: an updated review. Antioxidants, 2022, 11(2), 251.
[http://dx.doi.org/10.3390/antiox11020251] [PMID: 35204134]
[3]
Gromer, S.; Johansson, L.; Bauer, H.; Arscott, L.D.; Rauch, S.; Ballou, D.P.; Williams, C.H., Jr; Schirmer, R.H.; Arnér, E.S.J. Active sites of thioredoxin reductases: Why selenoproteins? Proc. Natl. Acad. Sci., 2003, 100(22), 12618-12623.
[http://dx.doi.org/10.1073/pnas.2134510100] [PMID: 14569031]
[4]
Reich, H.J.; Hondal, R.J. Why nature chose Selenium? ACS Chem. Biol., 2016, 11(4), 821-841.
[http://dx.doi.org/10.1021/acschembio.6b00031] [PMID: 26949981]
[5]
Lu, X.; Mestres, G.; Singh, V.; Effati, P.; Poon, J.F.; Engman, L.; Ott, M. Selenium- and tellurium-based antioxidants for modulating inflammation and effects on osteoblastic activity. Antioxidants, 2017, 6(1), 13.
[http://dx.doi.org/10.3390/antiox6010013] [PMID: 28216602]
[6]
Engman, L.; Al-Maharik, N.; McNaughton, M.; Birmingham, A.; Powis, G. Thioredoxin reductase and cancer cell growth inhibition by organotellurium antioxidants. Anticancer Drugs, 2003, 14(2), 153-161.
[http://dx.doi.org/10.1097/00001813-200302000-00009] [PMID: 12569302]
[7]
Tanini, D.; Ricci, L.; Capperucci, A.; Di Cesare Mannelli, L.; Ghelardini, C.; Peat, T.S.; Carta, F.; Angeli, A.; Supuran, C.T. Synthesis of novel tellurides bearing benzensulfonamide moiety as carbonic anhydrase inhibitors with antitumor activity. Eur. J. Med. Chem., 2019, 181111586.
[http://dx.doi.org/10.1016/j.ejmech.2019.111586] [PMID: 31401537]
[8]
Tanini, D.; Carradori, S.; Capperucci, A.; Lupori, L.; Zara, S.; Ferraroni, M.; Ghelardini, C.; Di Cesare Mannelli, L.; Micheli, L.; Lucarini, E.; Carta, F.; Angeli, A.; Supuran, C.T. Chalcogenides-incorporating carbonic anhydrase inhibitors concomitantly reverted oxaliplatin-induced neuropathy and enhanced antiproliferative action. Eur. J. Med. Chem., 2021, 225, 113793.
[http://dx.doi.org/10.1016/j.ejmech.2021.113793] [PMID: 34507012]
[9]
Sredni, B.; Caspi, R.R.; Klein, A.; Kalechman, Y.; Danziger, Y.; BenYa’akov, M.; Tamari, T.; Shalit, F.; Albeck, M. A new immunomodulating compound (AS-101) with potential therapeutic application. Nature, 1987, 330(6144), 173-176.
[http://dx.doi.org/10.1038/330173a0] [PMID: 3118216]
[10]
Kalechman, Y.; Albeck, M.; Sredni, B. In vivo synergistic effect of the immunomodulator AS101 and the PKC inducer bryostatin. Cell. Immunol., 1992, 143(1), 143-153.
[http://dx.doi.org/10.1016/0008-8749(92)90012-E] [PMID: 1623562]
[11]
Vrana, J.A.; Rao, A.S.; Wang, Z.; Jarvis, W.D.; Grant, S. Effects of bryostatin 1 and calcium ionophore (A23187) on apoptosis and differentiation in human myeloid leukemia cells (HL-60) following 1-beta-D-arabinofuranosylcytosine exposure. Int. J. Oncol., 1998, 12(4), 927-934.
[http://dx.doi.org/10.3892/ijo.12.4.927] [PMID: 9499457]
[12]
Ávila, D.S.; Colle, D.; Gubert, P.; Palma, A.S.; Puntel, G.; Manarin, F.; Noremberg, S.; Nascimento, P.C.; Aschner, M.; Rocha, J.B.T.; Soares, F.A.A. A possible neuroprotective action of a vinylic telluride against Mn-induced neurotoxicity. Toxicol. Sci., 2010, 115(1), 194-201.
[http://dx.doi.org/10.1093/toxsci/kfq036] [PMID: 20133376]
[13]
Ávila, D.S.; Palma, A.S.; Colle, D.; Scolari, R.; Manarin, F.; da Silveira, A.F.; Nogueira, C.W.; Rocha, J.B.T.; Soares, F.A.A. Hepatoprotective activity of a vinylic telluride against acute exposure to acetaminophen. Eur. J. Pharmacol., 2011, 661(1-3), 92-101.
[http://dx.doi.org/10.1016/j.ejphar.2011.04.031] [PMID: 21549114]
[14]
Tiano, L.; Fedeli, D.; Santroni, A.M.; Villarini, M.; Engman, L.; Falcioni, G. Effect of three diaryl tellurides, and an organoselenium compound in trout erythrocytes exposed to oxidative stress in vitro. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2000, 464(2), 269-277.
[http://dx.doi.org/10.1016/S1383-5718(99)00204-1] [PMID: 10648914]
[15]
Lin, T.; Ding, Z.; Li, N.; Xu, J.; Luo, G.; Liu, J.; Shen, J. Retracted: 2-Tellurium-bridged β-cyclodextrin, a thioredoxin reductase inhibitor, sensitizes human breast cancer cells to TRAIL-induced apoptosis through DR5 induction and NF-κB suppression. Carcinogenesis, 2011, 32(2), 154-167.
[http://dx.doi.org/10.1093/carcin/bgq234] [PMID: 21081474]
[16]
Cunha, R.L.O.R.; Gouvea, I.E.; Juliano, L. A glimpse on biological activities of tellurium compounds. An. Acad. Bras. Cienc., 2009, 81(3), 393-407.
[http://dx.doi.org/10.1590/S0001-37652009000300006] [PMID: 19722011]
[17]
Angeli, A.; Tanini, D.; Capperucci, A.; Supuran, C.T. First evaluation of organotellurium derivatives as carbonic anhydrase I, II, IV, VII and IX inhibitors. Bioorg. Chem., 2018, 76, 268-272.
[http://dx.doi.org/10.1016/j.bioorg.2017.12.010] [PMID: 29223030]
[18]
Tanini, D.; Capperucci, A.; Supuran, C.T.; Angeli, A. Sulfur, selenium and tellurium containing amines act as effective carbonic anhydrase activators. Bioorg. Chem., 2019, 87, 516-522.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.062] [PMID: 30928874]
[19]
Stefanello, S.T.; Gubert, P.; Puntel, B.; Mizdal, C.R.; Campos, M.M.A.; Salman, S.M.; Dornelles, L.; Avila, D.S.; Aschner, M.; Soares, F.A.A. Protective effects of novel organic selenium compounds against oxidative stress in the nematode Caenorhabditis elegans. Toxicol. Rep., 2015, 2, 961-967.
[http://dx.doi.org/10.1016/j.toxrep.2015.06.010] [PMID: 26726309]
[20]
Rooseboom, M.; Vermeulen, N.P.E.; Durgut, F.; Commandeur, J.N.M. Comparative study on the bioactivation mechanisms and cytotoxicity of Te-phenyl-L-tellurocysteine, Se-phenyl-L-selenocys-teine, and S-phenyl-L-cysteine. Chem. Res. Toxicol., 2002, 15(12), 1610-1618.
[http://dx.doi.org/10.1021/tx020034f] [PMID: 12482244]
[21]
Deng, Z.; Zhang, Y.; Yue, J.; Tang, F.; Wei, Q. Green and orange CdTe quantum dots as effective pH-sensitive fluorescent probes for dual simultaneous and independent detection of viruses. J. Phys. Chem. B, 2007, 111(41), 12024-12031.
[http://dx.doi.org/10.1021/jp074609z] [PMID: 17887667]
[22]
Chen, H.; Lesnyak, V.; Bigall, N.C.; Gaponik, N.; Eychmüller, A. Self-assembly of TGA-capped CdTe nanocrystals into three-dimensional luminescent nanostructures. Chem. Mater., 2010, 22(7), 2309-2314.
[http://dx.doi.org/10.1021/cm9032572]
[23]
Wachter, J. Metal telluride clusters — from small molecules to polyhedral structures. Eur. J. Inorg. Chem., 2004, 2004(7), 1367-1378.
[http://dx.doi.org/10.1002/ejic.200300935]
[24]
Zhang, B.; Hou, W.; Ye, X.; Fu, S.; Xie, Y. 1D tellurium nanostructures: Photothermally assisted morphology-controlled synthesis and applications in preparing functional nanoscale materials. Adv. Funct. Mater., 2007, 17(3), 486-492.
[http://dx.doi.org/10.1002/adfm.200600566]
[25]
Fonseca, S.F.; Lima, D.B.; Alves, D.; Jacob, R.G.; Perin, G.; Lenardão, E.J.; Savegnago, L. Synthesis, characterization and antioxidant activity of organoselenium and organotellurium compound derivatives of chrysin. New J. Chem., 2015, 39(4), 3043-3050.
[http://dx.doi.org/10.1039/C4NJ02329C]
[26]
Tanini, D.; Lupori, B.; Malevolti, G.; Ambrosi, M.; Nostro, P.L.; Capperucci, A. Direct biocatalysed synthesis of first sulfur-, selenium- and tellurium- containing L -ascorbyl hybrid derivatives with radical trapping and GPx-like properties. Chem. Commun., 2019, 55(40), 5705-5708.
[http://dx.doi.org/10.1039/C9CC02427A] [PMID: 31033970]
[27]
Ibrahim, M.; Hassan, W.; Meinerz, D.F.; Dos Santos, M.; V Klimaczewski, C.; M Deobald, A.; Costa, M.S.; Nogueira, C.W.; Barbosa, N.B.V.; Rocha, J.B.T. Antioxidant properties of diorganoyl diselenides and ditellurides: Modulation by organic aryl or naphthyl moiety. Mol. Cell. Biochem., 2012, 371(1-2), 97-104.
[http://dx.doi.org/10.1007/s11010-012-1426-4] [PMID: 22983825]
[28]
Capperucci, A.; Coronnello, M.; Salvini, F.; Tanini, D.; Dei, S.; Teodori, E.; Giovannelli, L. Synthesis of functionalised organochalcogenides and in vitro evaluation of their antioxidant activity. Bioorg. Chem., 2021, 110, 104812.
[http://dx.doi.org/10.1016/j.bioorg.2021.104812] [PMID: 33744808]
[29]
Kanda, T.; Engman, L.; Cotgreave, I.A.; Powis, G. Novel water-soluble diorganyl tellurides with thiol peroxidase and antioxidant activity. J. Org. Chem., 1999, 64(22), 8161-8169.
[http://dx.doi.org/10.1021/jo990842k] [PMID: 11674732]
[30]
Engman, L.; Stern, D.; Cotgreave, I.A.; Andersson, C.M. Thiol peroxidase activity of diaryl ditellurides as determined by a proton NMR method. J. Am. Chem. Soc., 1992, 114(25), 9737-9743.
[http://dx.doi.org/10.1021/ja00051a002]
[31]
Tanini, D.; Ricci, L.; Capperucci, A. Rongalite‐promoted on water synthesis of functionalised tellurides and ditellurides. Adv. Synth. Catal., 2020, 362(6), 1323-1332.
[http://dx.doi.org/10.1002/adsc.201901536]
[32]
Tanini, D.; Grechi, A.; Ricci, L.; Dei, S.; Teodori, E.; Capperucci, A. Novel functionalized organotellurides with enhanced thiol peroxidase catalytic activity. New J. Chem., 2018, 42(8), 6077-6083.
[http://dx.doi.org/10.1039/C8NJ00700D]
[33]
You, Y.; Ahsan, K.; Detty, M.R. Mechanistic studies of the tellurium(II)/tellurium(IV) redox cycle in thiol peroxidase-like reactions of diorganotellurides in methanol. J. Am. Chem. Soc., 2003, 125(16), 4918-4927.
[http://dx.doi.org/10.1021/ja029590m] [PMID: 12696911]
[34]
Press, D.J.; Back, T.G. Enhanced glutathione peroxidase activity of conformationally restricted naphthalene peri-dichalcogenides. Org. Lett., 2011, 13(15), 4104-4107.
[http://dx.doi.org/10.1021/ol201617t] [PMID: 21739953]
[35]
Jagdev, K.; Tanini, D.; Lownes, J.W.; Figliola, C.; Male, L.; Capperucci, A.; Grainger, R.S. Glutathione peroxidase mimics based on conformationally-restricted, peri -like, 4,5-disubstituted fluorene dichalcogenides. Org. Biomol. Chem., 2021, 19(48), 10565-10569.
[http://dx.doi.org/10.1039/D1OB02153B] [PMID: 34846405]
[36]
Braga, A.L.; Alberto, E.E.; Soares, L.C.; Rocha, J.B.T.; Sudati, J.H.; Roos, D.H. Synthesis of telluroamino acid derivatives with remarkable GPx like activity. Org. Biomol. Chem., 2009, 7(1), 43-45.
[http://dx.doi.org/10.1039/B814990A] [PMID: 19081943]
[37]
Detty, M.R.; Gibson, S.L. Tellurapyrylium dyes as catalysts for oxidations with hydrogen peroxide and as scavengers of singlet oxygen. Dihydroxytelluranes as mild oxidizing agents. Organometallics, 1992, 11(6), 2147-2156.
[http://dx.doi.org/10.1021/om00042a031]
[38]
Engman, L.; Stern, D.; Pelcman, M.; Andersson, C.M. Thiol peroxidase activity of diorganyl tellurides. J. Org. Chem., 1994, 59(8), 1973-1979.
[http://dx.doi.org/10.1021/jo00087a008]
[39]
Vessman, K.; Ekstroem, M.; Berglund, M.; Andersson, C.M.; Engman, L. Catalytic antioxidant activity of diaryl tellurides in a two-phase lipid peroxidation model. J. Org. Chem., 1995, 60(14), 4461-4467.
[http://dx.doi.org/10.1021/jo00119a024]
[40]
Engman, L.; Lind, J.; Merényi, G. Redox properties of diaryl chalcogenides and their oxides. J. Phys. Chem., 1994, 98(12), 3174-3182.
[http://dx.doi.org/10.1021/j100063a021]
[41]
Organoselenium Chemistry; Wirth, T., Ed.; Wiley-WHC Verlag & Co: Weinheim, Germany, 2012.
[42]
Lenardão, E.J.; Santi, C.; Sancineto, L. New Frontiers in Organoselenium Compounds; Springer: New York, NY, USA, 2018.
[http://dx.doi.org/10.1007/978-3-319-92405-2]
[43]
Bhabak, K.P.; Mugesh, G. Functional mimics of glutathione peroxidase: Bioinspired synthetic antioxidants. Acc. Chem. Res., 2010, 43(11), 1408-1419.
[http://dx.doi.org/10.1021/ar100059g] [PMID: 20690615]
[44]
Bhabak, K.P.; Mugesh, G. Amide-based glutathione peroxidase mimics: Effect of secondary and tertiary amide substituents on antioxidant activity. Chem. Asian J., 2009, 4(6), 974-983.
[http://dx.doi.org/10.1002/asia.200800483] [PMID: 19378298]
[45]
Mugesh, G.; du Mont, W.W. Structure-activity correlation between natural glutathione peroxidase (GPx) and mimics: A biomimetic concept for the design and synthesis of more efficient GPx mimics. Chemistry, 2001, 7(7), 1365-1370.
[http://dx.doi.org/10.1002/1521-3765(20010401)7:7<1365::AID-CHEM1365>3.0.CO;2-Y] [PMID: 11330888]
[46]
Bhowmick, D.; Mugesh, G. Introduction of a catalytic triad increases the glutathione peroxidase-like activity of diaryl diselenides. Org. Biomol. Chem., 2015, 13(34), 9072-9082.
[http://dx.doi.org/10.1039/C5OB01294E] [PMID: 26220806]
[47]
Tripathi, S.K.; Patel, U.; Roy, D.; Sunoj, R.B.; Singh, H.B.; Wolmershäuser, G.; Butcher, R.J. o-hydroxylmethylphenylchal- cogens: Synthesis, intramolecular nonbonded chalcogen...OH interactions, and glutathione peroxidase-like activity. J. Org. Chem., 2005, 70(23), 9237-9247.
[http://dx.doi.org/10.1021/jo051309+] [PMID: 16268596]
[48]
Tanini, D.; Grechi, A.; Dei, S.; Teodori, E.; Capperucci, A. An easy one-step procedure for the synthesis of novel β-functionalised tellurides. Tetrahedron, 2017, 73(38), 5646-5653.
[http://dx.doi.org/10.1016/j.tet.2017.07.061]
[49]
Tanini, D.; Borgogni, C.; Capperucci, A. Mild and selective silicon-mediated access to enantioenriched 1,2-mercaptoamines and β-amino arylchalcogenides. New J. Chem., 2019, 43(16), 6388-6393.
[http://dx.doi.org/10.1039/C9NJ00657E]
[50]
Pascoe, D.J.; Ling, K.B.; Cockroft, S.L. The Origin of Chalcogen-Bonding Interactions. J. Am. Chem. Soc., 2017, 139(42), 15160-15167.
[http://dx.doi.org/10.1021/jacs.7b08511] [PMID: 28985065]
[51]
Nascimento, V.; Alberto, E.E.; Tondo, D.W.; Dambrowski, D.; Detty, M.R.; Nome, F.; Braga, A.L. GPx-Like activity of selenides and selenoxides: Experimental evidence for the involvement of hydroxy perhydroxy selenane as the active species. J. Am. Chem. Soc., 2012, 134(1), 138-141.
[http://dx.doi.org/10.1021/ja209570y] [PMID: 22136421]
[52]
Kheirabadi, R.; Izadyar, M. Computational modeling of the kinetics and mechanism of tellurium‐based glutathione peroxidase mimic. Int. J. Quantum Chem., 2020, 120(12), e26201.
[http://dx.doi.org/10.1002/qua.26201]
[53]
Sarma, B.K.; Manna, D.; Minoura, M.; Mugesh, G. Synthesis, structure, spirocyclization mechanism, and glutathione peroxidase-like antioxidant activity of stable spirodiazaselenurane and spirodiazatellurane. J. Am. Chem. Soc., 2010, 132(15), 5364-5374.
[http://dx.doi.org/10.1021/ja908080u] [PMID: 20345146]
[54]
Back, T.G.; Kuzma, D.; Parvez, M. Aromatic derivatives and tellurium analogues of cyclic seleninate esters and spirodioxyselenuranes that act as glutathione peroxidase mimetics. J. Org. Chem., 2005, 70(23), 9230-9236.
[http://dx.doi.org/10.1021/jo0512711] [PMID: 16268595]
[55]
Poon, J.; Singh, V.P.; Engman, L. In search of catalytic antioxidants--(alkyltelluro)phenols, (alkyltelluro)resorcinols, and bis (alkyltelluro)phenols. J. Org. Chem., 2013, 78(12), 6008-6015.
[http://dx.doi.org/10.1021/jo400703w] [PMID: 23701313]
[56]
Amorati, R.; Valgimigli, L.; Dinér, P.; Bakhtiari, K.; Saeedi, M.; Engman, L. Multi-faceted reactivity of alkyltellurophenols towards peroxyl radicals: Catalytic antioxidant versus thiol-depletion effect. Chemistry, 2013, 19(23), 7510-7522.
[http://dx.doi.org/10.1002/chem.201300451] [PMID: 23576474]
[57]
Singh, V.P.; Poon, J.; Engman, L. Catalytic antioxidants: Regenerable tellurium analogues of vitamin E. Org. Lett., 2013, 15(24), 6274-6277.
[http://dx.doi.org/10.1021/ol403131t] [PMID: 24279415]
[58]
Ren, X.; Xue, Y.; Liu, J.; Zhang, K.; Zheng, J.; Luo, G.; Guo, C.; Mu, Y.; Shen, J. A novel cyclodextrin-derived tellurium compound with glutathione peroxidase activity. ChemBioChem, 2002, 3(4), 356-363.
[http://dx.doi.org/10.1002/1439-7633(20020402)3:4<356::AID-CBIC356>3.0.CO;2-O] [PMID: 11933237]
[59]
McNaughton, M.; Engman, L.; Birmingham, A.; Powis, G.; Cotgreave, I.A. Cyclodextrin-derived diorganyl tellurides as glutathione peroxidase mimics and inhibitors of thioredoxin reductase and cancer cell growth. J. Med. Chem., 2004, 47(1), 233-239.
[http://dx.doi.org/10.1021/jm030916r] [PMID: 14695837]
[60]
Jiao, A.; Yang, N.; Wang, J.; Xu, X.; Jin, Z. Cyclodextrin-derived chalcogenides as glutathione peroxidase mimics and their protection of mitochondria against oxidative damage. J. Incl. Phenom. Macrocycl. Chem., 2013, 75(1-2), 155-163.
[http://dx.doi.org/10.1007/s10847-012-0156-2]
[61]
Wang, L.; Qu, X.; Xie, Y.; Lv, S. Study of 8 types of glutathione peroxidase mimics based on β-cyclodextrin. Catalysts, 2017, 7(10), 289.
[http://dx.doi.org/10.3390/catal7100289]
[62]
Morya, V.K.; Dong, S.J.; Kim, E. Production and characterization Te-peptide by induced autolysis of Saccharomyces cerevisiae. Appl. Biochem. Biotechnol., 2014, 172(7), 3390-3401.
[http://dx.doi.org/10.1007/s12010-014-0780-y] [PMID: 24532446]
[63]
Mao, S.; Dong, Z.; Liu, J.; Li, X.; Liu, X.; Luo, G.; Shen, J. Semisynthetic tellurosubtilisin with glutathione peroxidase activity. J. Am. Chem. Soc., 2005, 127(33), 11588-11589.
[http://dx.doi.org/10.1021/ja052451v] [PMID: 16104720]
[64]
Liu, X.; Silks, L.A.; Liu, C.; Ollivault-Shiflett, M.; Huang, X.; Li, J.; Luo, G.; Hou, Y.M.; Liu, J.; Shen, J. Incorporation of tellurocysteine into glutathione transferase generates high glutathione peroxidase efficiency. Angew. Chem. Int. Ed., 2009, 48(11), 2020-2023.
[http://dx.doi.org/10.1002/anie.200805365] [PMID: 19199319]
[65]
Bortoli, M.; Torsello, M.; Bickelhaupt, F.M.; Orian, L. Role of the chalcogen (S, Se, Te) in the oxidation mechanism of the glutathione peroxidase active site. ChemPhysChem, 2017, 18(21), 2990-2998.
[http://dx.doi.org/10.1002/cphc.201700743] [PMID: 28837255]
[66]
Vernekar, A.A.; Mugesh, G. Catalytic reduction of graphene oxide nanosheets by glutathione peroxidase mimetics reveals a new structural motif in graphene oxide. Chemistry, 2013, 19(49), 16699-16706.
[http://dx.doi.org/10.1002/chem.201303339] [PMID: 24281813]
[67]
Yu, F.; Li, P.; Wang, B.; Han, K. Reversible near-infrared fluorescent probe introducing tellurium to mimetic glutathione peroxidase for monitoring the redox cycles between peroxynitrite and glutathione in vivo. J. Am. Chem. Soc., 2013, 135(20), 7674-7680.
[http://dx.doi.org/10.1021/ja401360a] [PMID: 23621710]
[68]
Thomas, J.; Dong, Z.; Dehaen, W.; Smet, M. Selenium/tellurium-containing hyperbranched polymers: Effect of molecular weight and degree of branching on glutathione peroxidase-like activity. Macromol. Rapid Commun., 2012, 33(24), 2127-2132.
[http://dx.doi.org/10.1002/marc.201200519] [PMID: 22996964]
[69]
Yin, Y.; Jiao, S.; Zhang, R.; Wang, X.; Zhang, L.; Yang, L. Construction of a soluble supramolecular glutathione peroxidase mimic based on host-guest interaction. Curr. Organocatal., 2015, 2(1), 64-70.
[http://dx.doi.org/10.2174/2213337202666150121230931]
[70]
Yin, Y.; Jiao, S.; Lang, C.; Liu, J. A supramolecular microgel glutathione peroxidase mimic with temperature responsive activity. Soft Matter, 2014, 10(19), 3374-3385.
[http://dx.doi.org/10.1039/c3sm53117a] [PMID: 24652520]
[71]
Yu, S.; Yin, Y.; Zhu, J.; Huang, X.; Luo, Q.; Xu, J.; Shen, J.; Liu, J. A modulatory bifunctional artificial enzyme with both SOD and GPx activities based on a smart star-shaped pseudo-block copolymer. Soft Matter, 2010, 6(21), 5342-5350.
[http://dx.doi.org/10.1039/c0sm00162g]
[72]
Jiao, S.; Liang, X.; Zhang, R.; Zhong, S.; Zheng, Y.; Wang, S.; Liu, M.; Hu, X.; Yin, Y. Facile construction of microgel based biomimetic glutathione peroxidase with temperature responsive catalytic activity. ChemistrySelect, 2019, 4(41), 12143-12150.
[http://dx.doi.org/10.1002/slct.201903025]
[73]
Nogara, P.A.; Rocha, J.B.T.; Bortoli, M.; Orian, L. Biological activity of synthetic organoselenium compounds: What do we know about the mechanism? Curr. Chem. Biol., 2022, 16(1), 12-24.
[http://dx.doi.org/10.2174/2212796816666220422135204]

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  • Booting (111ms)time
  • Application (260ms)time
  • 1 x Application (70.19%)
    260ms
    1 x Booting (29.81%)
    111ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.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.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.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
    31 statements were executed, 4 of which were duplicates, 27 unique. Show only duplicated186ms
    • 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 ('873352086','',1,1740528204,1740528204) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740528204
      1.03msalphaeurekaselec_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 ('873352086','/article/127719',1,1740528204,1740528204)
      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 >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) 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 >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) 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 >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) 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 >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) 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 >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) 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 >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 873352086 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 873352086) limit 1
      13.6msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 873352086
      • 1: 873352086
      • 2: 873352086
      • 3: 873352086
      • 4: 873352086
      • 5: 873352086
      • 6: 873352086
      • 7: 873352086
      • 8: 873352086
      • 9: 873352086
      • 10: 873352086
      • 11: 873352086
      • 12: 873352086
      • 13: 873352086
      • 14: 873352086
      • 15: 873352086
      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=127719
      1.18msalphaeurekaselec_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` = 71 limit 1
      770μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 71
      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=71) and sj.journal_id!=71 group by `j`.`nid`) as `aggregate_table`
      730μsalphaeurekaselec_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=71) and sj.journal_id!=71 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      660μsalphaeurekaselec_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=71) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      35.8msalphaeurekaselec_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=71) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      66.67msalphaeurekaselec_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` = '127719'
      400μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 127719
      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` = '127719'
      3.22msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 127719
      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` = '127719' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.82msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 127719
      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
      290μsalphaeurekaselec_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
      630μsalphaeurekaselec_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 = 71 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      46.14msalphaeurekaselec_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 = 71 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      2.93msalphaeurekaselec_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 = 71 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      2.18msalphaeurekaselec_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` = 127719 limit 1
      160μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 127719
      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 = 127719 and content_type = 'article' order by status desc limit 1
      210μsalphaeurekaselec_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` = 211086 limit 1
      170μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 211086
      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
      180μsalphaeurekaselec_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` = 'CCB' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      260μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: CCB
      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 = '127719' 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) )
      370μsalphaeurekaselec_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` < '13' and is_uploaded = 1 and issue_id = 12302 order by cast(first_page as SIGNED) desc limit 1
      410μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 13
      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` > '25' and is_uploaded = 1 and issue_id = 12302 order by cast(first_page as SIGNED) asc limit 1
      380μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 25
      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'
      150μsalphaeurekaselec_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
      180μsalphaeurekaselec_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` = 127719 limit 1
      2.29msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 127719
      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` = 71 and `b`.`banner_from_date` <= 1740528204 and `b`.`banner_to_date` >= 1740528204 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.15msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 71
      • 3: 1740528204
      • 4: 1740528204
      • 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` = 71 and `b`.`banner_from_date` <= 1740528204 and `b`.`banner_to_date` >= 1740528204 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.06msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 71
      • 3: 1740528204
      • 4: 1740528204
      • 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='d4edc4b4ad05f795cd7ba78275e3d68a'
      220μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
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        ClearShow all
        Date ↕MethodURLData
        #12025-02-26 00:03:24GET/article/127719414311